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57.16
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ISBN 978-5-8948-1822-1


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ISBN 978-5-8948-1822-1

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....................................... ................................................................................................. 10
......................................... ............................................................................................... 18
1.

(-).............................................................................................................. 21
1.1. -................................................. 21
1.2. ................................. 37
1.3. -......................................................... 38
1.3.1.

-................................................................................. 44
1.4. -..................................................... ......................... 50
1.5. -............... 56
1.5.1.

-................................................................................. 59
1.5.2.
-............... 62
1.5.3.
-................................................ 63
1.6 . ................... 64
1.6 .1.
......... 64
1.6.2.

....................................................................................... 65
1.7. -............................. 65
1.7.1.
.............................. 69
1.7.2.


............................................ 75
1.7.3.

-...................... 80
1.8. -.................................................................................... 81
1.9. -..................102
1.9.1.

............................................................................ 112

2.

1.10. -
.................................. 117
1.10.1.

............................... 120
1.10.2.

............;..... ..................... ...................... 132
1.10.3.
............................ ........................... ....... 140
1.10.4.
-.................................................................... 143
1.10.5.
HELLP-..............................................................................151
1.10.6.
............. ............ ..................................... 155
1.10.7.
............................................................................... 155
1. 11 . ........................................ 155
1.11.1.
- ........... 159
1.12. - ..............................................
1.13. - .
() ............................................ 164
1.14. ....................172
1.15. .............................. 185
1.15.1.
()............ 188
1.16. - ...................................................190
1.16.1.
.............................190
1.16.2.
- .............................................. 191
1.16.3.

........................................................ 194
1.16.4.

..............................204
1.16.5.
...................217
1.17. ,
-..............................................................220
............................ ............................ ......................................................,^..230
()..........................................................................238
2.1. .............................................................................238
2.2. .... .............................................................. 239
2.3. ........................................................................................242 j
2.4. ...................................................................... 248
2.4.1.
............................................. 249
2.4.2.
- ..................................... 252 J
, 2.4.3. , ............................................................256 1
2.4.4.
..............................................................259
2.4.5.
...................................................261 |
2.4.6.
...................................... 262 |
2.4.7.
..........................................262 1
2.4.8.
....................................................... 264
2.5. ...................................................................................................266 I
2.5.1

: , ,
................................................................... 266
2.5.2.
......... 27(
2.5.2.1.
( )............................270 8
2.5.2.2.
.............................................................................. 280

3.

2.S.2.3. ......................... 283


2.5.2 ................................................................... 287
2.5.2.5. .......290
2.5.2.6.
- ............................... 294
2.5.3.
- ........................ 298
2.5.4.
............................304
2.6. ............................................... ..............................................308
2.7. ..................................... ........................................... 314
2.7.1.

..................................................................... 316
2.7.2.
............................... 320
2.7.3.

...........................................................................321
2.7.4.

...........................................................................326
2.7.4.1.
.................................. 326
2.7.4.2.
.............................................................338
2.7.4.3.
....................................................340
2.7.5.

.............................................................................342
2.7.6.
..................343
2.7.7.

............. .................................................. 345
2.7.8.
.................346
2.8. ........................................................ ........................... 347
.....................................................................................................................349
, - ,
,
- ............................................................................... 359
3.1. ().................................................................. 359
3.1.1.
...............................................................................359
3.1.2.
.............................................................. 360
3.1.3.
............................................................... 362
3.1.4.
............................................................................................366
3.1.4.1.
................................ 374
3.1.4.2.
............................................................. 374
3.1.4.3. .................377
3.1.4.4. ................................. 378
3.1.4.5.
. ................380
3.1.4.6.
................................................................................. 382
3.1.4.7. ............ 383
3.1.5.
.................................................. 386
3.1.6.
.......................................................................... 388
3.1.7.
................... 394

1.8.
...............................................................
3.1.9.
..................................................................................................
3.2. - ( )...................................404
3.2.1.
.......... ................ ................ ...... ............. .................. 404
3.2.2.
............. ..................................................................
3.2.3.
.
...................................................... ..
3.2.4.
............................................... ..
3.2.5.
.............................................. | j j
3.2.6.
I I .............................................................. 430
3.2.7.
...................... 437
3.3. ()
- ( ).................................................. 439
3.3.1.
, , ..... 439
3.3.2.

/.................... ....................................................................... 443
3.3.3.
/ ............................ 447
3.3.4

/ ..................... ................................................. 451
3.3.5.
/ ........................456
3.3.6.
/........................................... 457
3.3.7.
/ ........................................................459
.......................................... ..... .................................................................... 465
(M Q . . ........474
4.1. ( )....................................................................... 474
4.1.1.
.................... ............. .............................................. 474
4.1.2.
. ! .................................................. 477
4.1.3.
.......479
4.1.4.
................................................. ....................................481
4.1.5.
............................................................... 482
4.1.5.1. ................. ...........................484
4.1.5.2. ................... 485
4.1.5.3. ...............................488
4.1.5.4.
................. ..................................492
4.1.5.5.
................................................... 493
4.1.5.5.1.
..............................................493
4.1.5.5.2. .......... 495
4.1.5.5.3.
......................................................501
4.1.5.5.4.
.................................................. 509
4.1.5.5.5. ,
................ 512
4. 1 .5.5.6.
......................................................... 513
4 . 1 .5.5.7.
,

......................... 515

4.

5.

4 .1.5.5.8.
................................. 520
4.1.5.5.9. ,
.......... 520
4.1.6. ............... ..... ............................... .......................................... 527
4.1.7.
................................................ 529
4.2. , ........... 539
4.2.1.
,
(),
, ......................................... 544
4.2.1.1. ................................................................ 547
4.2.1.2. ........................................... 563
4.2.1.3. ............................................................ 576
4.2.1.4. ............................................... 579
4.2.2:
, ..................................................... 595
4.2.3.


..................... .....................................................608
....................... ............... ....... .............................. ..................................... 615
.....................................630
5.1. ...................................................................................... 630
. 5.2. ...................................................................... .......................... 631
5.3.
......... ................... ....... ................................................634
5.4.
......................................................................................635
5.4.1.

........................... 639
5.4.2.
,
.......................................................... 655
5.4.3.
.................... 673
5.5. - ................... 681
5.6. -
.......................................................694
5.7. , ,
...................................................................700
5.8. , ..................................... 705
5.9. ........ 706
5.10. ..............................................................711
5.11.
........ ........ J ....... .....;........................... 714
5.12.
....................... .......................................................... 716
5.12.1.
............................................................... 717
5.12.2.
...................................... 719
5.12.3.
................:................................................... 720
5.12.4.
............................................... 723
5.12.5.
.
....................................... 741
5.12.6.
-.................................. ..... ............................ 748
5.12.7.
...................... 751
5.13. HELLP- ........... 757

6 .

7.

O r

5.14.
.................................................................. 7gg
5.15. ................................ 771
5.16.
....;......................... ............ ............................................ 775
.......... ................ ................. ..... ......................................................................780

............................................. 795
6 .1.
( ) ..........795
6.2. ................................................................. 798
6.2.1.
........................ 798
6.2.2.
......................... 799
6.2.3.
,
........................................................................... 800
6.2.4.
................. 802
6.2.5.
...................................804
6.2.6.
.......807
6.3.
................................... ...... ....................809
6.3.1.
........ ............................................;*<*809
6.3.2.
.............................. 810
6.3.3.
........... 812
6.3.4.
......................814
6.3.5.
.......816
6.3.6.


818
6.3.7.

............................................ 819
6.3.8.

........ ............................................................ 821
6.3.9.
-
................................................................826
6.3.10.

..........................830
6.3.11.



831
6.3.12.


....... ......................................................... 834
6.3.13.

............................................ ..1.. ; ......:.......... .................. 836
6.4.
.................. ..... ....;.
...
.&............................ ..................... 843
6.5. .............................. 846
6 .6 .
. , ................................849
............... ....... .............. .............................................. .................................... 854
......................................................... 864
7.11 ................................................................. 864
7.2. ........................... *........................... 871
7.2.1.
.................................................. 871
7.2;2.
............................................................... .................................... 872

7.2.3.
................................................................................873
7.2.4.
..............................................................873
7.3. :
.................. 874
7.3.1.

............................................... ................... ....... 876
7.3.2.

........................ 879
7.3.3.
, -
........................ 881
7.4.
.....................................................................................883
......... ............................. ....... ......................................................................... 885



ACT
II
AT II
AT III
III


AT III
III

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17--
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Arg

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CARS

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dRW T
deluted Russell viper venom time (
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EDHF

ED R F

EGF

ELISA
enzyme linked immunosorbent assay (
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EPC R
C/APG
EPR-1
effector cell protease receptor ( 1)
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FG F-P
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FV Leiden
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HAIR

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HLA
human leucocyte antigenes
HLA-DR II
HS

HUVEC
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IgE

IGF

IgG
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IgG
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killer-activator receptor
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killer-inhibitor receptor
LAK
lymphokine-activating killers
LPB

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NAP-2
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NFkB

NK- natural killers (- )
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NOS
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plasm nogene activator inhibitor I (
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PAT

PC

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PG


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PIBF
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PS
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RR
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T-cell receptor
tissue factor ( )


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tissue plasminogene activator (
t-PA
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Trp
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TSP-1
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VCAM-1 -1

VEGF

VPF

vWF

WHO


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1.1




Neisseria meningitidis

Enterobacteriaceae sp.

Salmonella sp.

Haemophilus sp.

Pseudomonas sp.


/
Pneum ococcus

Staphylococci

Hemolitic streptococci

-
Clostridium sp.

Mycobacterium tuberculosis
III



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-
Aspergillus sp.

Histoplasma sp.
( )
Candida sp.




:

IX

IX

XI

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.
,

:
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40

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.

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41

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42

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43

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44

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45

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46

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.
.
:
.
PAI-1.
.
.
(t- ).
1+2 (F I+ 2 ), - (-) -.

( 2
):
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( 90 );
( 20, 02 32 Hg);
12 4;
:
;
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;
;
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.

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1.

47
1.2

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;
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; -
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).
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48


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49

()
, /
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:
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2) ,
8 .
:
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;
2) .
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() ;
+ (
);
(, , );
(, , , ).
2 % ,
0,2% .
:
1) ,
(-);
;
2) (-);
, .
, :
) () Conley Hartman.
Ig ( IgG, IgA,
IgM), in vitro -
, ,
.
, V,
X, ',
) () 1983 . Harris, Gharavi
. , IgG
.
) V, , .
-:
1) *
;
2)
;

50

3) ;
4) ,
;
5) .
:
1. ,

.
2.

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3. ,

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.
-
- :
1) , ;
2) , ;
3) , .

.
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:
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( III, ).
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:

.

1.4. -
I.

.
.
().
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1) ,
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,
;

1.

51

2) - -1, -6 ,

, .
, .
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L-;
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;
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,
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( ).
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:
-, ;

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.
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9080 10 ,
, ,
60 10 .

Vila ,
III (AT III), , S.
, :
1) ;
2) (
);
3) , . .
, ;
4) (,
),
;
| | .
(TFPI)
; .
TFPI - .

52

III -:
1) III 80% ;
2) III
,
;
3)
III 40-60%;
4) - III

;
5) 111
-;
6) - - , ,
III;
7) III
, - .
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1)
S ;
2) , ,
;
3)
(,
);
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:
Va Villa;
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;
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.

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( )
( ).
II.


-,
, .
:
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1.

53


-, -
.
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;
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, ,
;
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, (
,
);
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;
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;
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;
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(, ,
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4) , ,
;

, ,

-1 (PAI -1).

54

6) ,
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.

,
.
, :
1. ( ) ,
.
2.
, .
3. ,
.
4.
.
5.
: 1)
; 2) ,
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6. :
) -
2 -3 A (FPA)
FI +2,
60% .
;
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;
)
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,
.
7. ,

.
,
, .
8. 4 (
), S,

.

,
.

III.

55

- (
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,
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.


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.
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.

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.

56


, - :
;
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1.5.
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57

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;
;
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58

;
;
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.
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1) ()
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2) ;
3)
, -;
4) /
- (, ,
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;
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6)
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-
1. :
5575 % ;
(
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.
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.
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,
,

' 1

59

,
;

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60

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61


;

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.
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,
.
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1015%
(Brain Hourihane);

;
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90% ;
,
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1) 10-15% -
. -.
;
2) -
. ,
.

62

.
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3) .
1.5.2. -

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______ -_______


-
__________________________________


________________________
HELLP-
____________

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.
2.
.

.
3. ,
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;
;
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1. ___________________ 63

;
.
-
, 10%
.
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1.
.
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.
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(Fl+2, ).
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5. .
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.
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1. - -.
2. () ,

.

64

- --

3. II III .
,
, .
4. ,
,
I II .
5. .
6. , .
7. .
8. 40% .
9. , ATIII, 50%
.
10. F1+2, , ,
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1 ___________ 65
5.

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1.6.2.

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66

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4
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68

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;
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);
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.
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69

1.7.1.

():
1)
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;
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III (AT III);
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ELISA-
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4 ;

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;
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AT III.
:
;
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,
;
FPA
;
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;
FPA ELISA-;
FPA
in vitro
;
FPA ( 3 5 ),
;
F1 +2 (90 )
, FPA;
F1+2 in vitro , FPA.

70


:
1) F1+2 FPA
;
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;
3) .
:
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;
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;
4)
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in vivo.

;
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:
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;
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;
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1.

71

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; .

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PF4 p-T G ,
:
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.

:
;
;
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R. . 1998 .
:
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:
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:
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72

:



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:
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77

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79

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80

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82

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85


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25 00030 000 / , 10 000
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15 00020 /
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1000 / 5000 4

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.
III :
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.
2.

90

>

, 80 000100 5% 10.

3.

.
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2 5% 5,0-10,0 68 .
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, .
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,
.
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8. ,
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,
.

.
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:
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.
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11.

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91



.
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92

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23.
,
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200,0-300,0
.
24. ,


III.

25. AT III
.
AT III
54 77%, AT III.
26. AT III
96-129%
.
()
.
27.
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.
28.
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29. 15 00020 000 / , ,
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^ 1.

93

3)

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96

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11. 150,0200,0
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10,00020,000 / ,
.
16.

97

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17.
( 4 .) ,
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100

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(15,000-20,000/) (150 ICU/)
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102


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103

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104

:
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:
1. VII, X
, I .
2. FVII 80% 70%.
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.
4. FIX FXII , , FXI
.
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.
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7.
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8. 1620 .
.
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() 3336 .
10. (3740 .)
.
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( I) 4 /.
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,
.
4. ( II III )
,
( VIII, IX, X,

XII).

.

' *"
- . - .
--------------- ----- ----

ffffl

105

5
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.


.
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106

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, 195 4,3 109/.
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.
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___ ___

_____ _______________
_
-------------- ---------- ---------------------- ---------------------

{0 2 JJ2 Z 2 Z .---------- -----------------------------------------------------------------------------------

107

---------------------------------------

, -, 5-,
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(F1+2) ()
, ,
.

.
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.

:

1)
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2) 75-80%
;
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;
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III , AT III;
5) AT III
,
;
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;
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( ) (
);
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III, ,

;
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;
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III ,
.
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108

(-) 1:

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.
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.
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,
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.

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.
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4.
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.
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.
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.
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110

.
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15-20
250 ) ^
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.
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111

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.
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112

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113

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114

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FV Leiden, G20210A, MTHFR 677,
PAI-1,
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115

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.
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11.
:

116

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, ,

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.
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1982 . ,
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117

21. ()


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.
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.
26.
2024 . .
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.
27.
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.

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28.

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1.10.
-


1.
,
. , ,
.

118

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.
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.
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.
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7. (
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100%.
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? 1

119





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.
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, , ;

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.
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120

1.10.1.

.
()
.
, ,
.
1926 . . 1941 . Steiner Luschbaugh
, ,
.
. Liban Raz 1969 .
, , ,
. Thompson Budd 1963 . ,
, .
300 .
,
,
I II [Resnik, 1976; Guidotti
1981; Cromley, 1983; Bowes, 1983].

Steiner Luschbaugh 1941 .
,
.
,

[Clark, 1995].
, ;
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. ,
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.
,
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( 1.6 ).
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()


( )

fnaR 1. __________ 121


.
,
.
, , , ,
(Parker,
1980; Smith, 1980; K a p in Ferguson, 1985; Lee, 1988; Parillo, 1993].
,
, ,
[Kapin, Ferguson, 1985]. ,
[Parker, 1980].
, 4 1%
[Clark, 1995].


[Clark, 1985]. 1986 . Azegami Mori ,

.
, ,
. ,
, , , .
1.
.
, .
2. 1:8000 1:80 .
3.
,
.
4. ,


.
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;
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122

( .
.
).

30

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20%
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;
210 390 %;
;
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;
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, ,
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.
, (50%
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)
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).
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().

1- _________ 12 3

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124

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1.7.


.
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1972). Philips Davidson ,
,
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,
[Clark, 1995].

.

125

1.7.

, , ,
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[Clark, 1995]. , ,
,
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.

126



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.

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127

t : ,
.
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;
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.

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.

128

, .
.
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.
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.


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.
100 /
6, 100150 / 1224.


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.
.

1.


2.



3. -
()

1.

129

()

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( )



, :
1) ;
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:
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:
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;
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.
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).
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1 30

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500700 /.
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.
7. ,
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.
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, ,
.
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.
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250 000500
100 000-200 /
.
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.
14. ,

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.
15.

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;

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131

3) ,
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0 .
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3OS, - . XIII
.
.

., 30 . 06.03.1991 . 5 .
: 4041 .
. I , .
14.03.91, 9-
.
4- .
. . .
170 . 86 . 110 . 44 .
: 5 , 3 .
1981 . , 4200 .
1983 . , 4000 .
1983 . , /.
1985 . , 4200 .
1991 . .
, 11 -II
, .
, , .
1985 . 3- , ,
.
5 30 . 120/80-110/70 .., 78 ./,
, . ,
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6 .
7 00 . , 4200 , 52 ,
8 . , .
7 10 . , 25x28 .
.
150-200 . 1,0 /.

, .
*. 30 . 120/90-130/100 .., 98 ./ ,
90/60 .., 100 ./.
, (
).

Cito!
0 2.
S. Euphyllini 10,0 /

132________________

- ,

S. Corglyconi 10,0 /
. 10,0 /
S. Prednisoloni 30 /
S. Dropcridoli 30 /
S. 2% 1,0 /
S. Suprastini 2,0 /
S. Methacini 0,5 /
S. Dibazoli 2,0 /
S. Papaverini 2,0 /
, 810 :
, , ,
, . , 1820 .
, , ,
.
120/80 .., 88 ./, .
.


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.
1.10.2.

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1.

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ggj

133

, ,

.
2.
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3. :
;
;

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, , , );

;
I , (
V Leiden, AT III, ,
.).
4. :
46% ;
21% ;
I 55,6% ;
44% .
5. (. 1.5):
1.5

.
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.
.

()

.
, ,
. . - . 3 0 %

.
1. :
;
;
.

.
Placenta praevia.
2. :
;
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( );
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134

;
;

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.
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;
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)
.
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;
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, ;
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;
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.
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8.
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;

135


;
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136_______________

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3) , *
;
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13. :
(
X - Y - );
(
(
30% ,
1,5 / 2,0-3,5 / 10% ,
1,75 / 15% );
: ;
AT 111( AT III
5276% , ,
0,310-0,343 /);
(
);
()
( 25% );
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(,
, ).
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.
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.
15.

.
16. () -

:

_______ 137
n

80 000-100 , 20 000 /;
5% / 5001000 (2000)
, 250-500 /, /;
2)

II III :

200,0-400,0
(500,0600,0 ) 10 / .
17.
:

+ 5001000 /, 12-
25005000 4
15 00020 000 /.;

(150,0200,0 )
AT III
5477%.
18.
- I ,
- ,


.
19. :
,
.
,
34-36 . ,
, .
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4 .

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,
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138

,
. :


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.
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.

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.
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.
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.
24. :
;
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25.
.
600700 .
.
26. , :

139

+ , 3: /;
+
;
(
46 );
.
27. 300 /,

.
150/
.
28. ,
.
.
:
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46 (
1 ) .
2 ;
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, 12
;
3)
(300
1 ) (8000 / 3 1 ).
29. , . :
| ;
.

.
30. :
;
;
;
;

;

.
31. , :
-
.
2-.

.

140

1.10.3.
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. ,
.
, ,
, , .
1.
, , 23 .
2. , (,
, , .),
-
.
3.
.
4. :

1)

:
1,5 / 1,85 / (
2,0-3,3 /);
85112
7598 (: 6070 2040 );
6880%;
2)
;
3) ,
:
4061 103/;
;
4) :
AT III 5486% ( 100120%);
4060 10 / ( 3 10 /)
.
5.
:

;
;
; *
AT III
(X Y)
1632 103/.
6.

-,
.

j __________ 141

7 :
1)
, -
,

;
2 ) (1,25 /
15 /) ,
300,0 ;
3 ) 900,0
1200 ,
;
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80 000100 000 / ;
5)

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(, , );
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.
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;

142

3) AT III , ;
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.

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.
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.

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:

1) ;
5000-10 000
45 ;
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;
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(200,0-400,0 ).
13. :

, ;


;
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_________ 143
1.10.4.

1. , , 1,5
23,2%.
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144

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145

.
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.

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,
.
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III .

( MTHFR 677,
V Leiden).

146

., 31 . : 5 .
. .
: . 1993 .
32 .
950 , 37 , 4- . 1998 .
2627 . 1000 2- . ^ :
9.12.98
, , 2627- II .
. : 38 ( 2040 ), 106%, +/, - = 1./ (N
0,5 /), .
, , 65, 86% 57%
.
,
,
,
: MTHFRC667T, FV Leiden, PtG202l0A.
7 . -
MTHFR C667T.
: 31,52
N 8-10/. :
78 . . . .
( MTHFR 667).
.
0,3 /, 4 /, , 1 , (-3 12 ).

,
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.
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37-
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,
67 . 48 ,
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, 10 . 67 :
37 . -. .
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2700 , 47 . 7/7 .

pfflpfl 1. __________ 147


,

32 27 . .

, .
,
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M TH FR 667 ( )
.
,
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.

., 45 . 67 : 26 .
. I .

. .
: . ,
1993 ., 32 .,
. 1994 .
10 . , ,
1015 .
, 200/100 .. , .
. : ,
, .
. .
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. - ( +++, - + + > 3 / N =
=0,5 /).
.
.
: 26 . .
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FVLeiden, 20210 MTHFR 667.
FV Leiden. :
.
: .
. - ( ; -
, F1+2).
: 2930 . .
III . . .
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148

,
30 . .

30 .
. , 1600 , 2- .
6
5000,
- 10 .


V Leiden . ,
, . (
III ) V Leiden
,
.
:
;
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, ;
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:

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;

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,
;

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;
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. ,,
;

.

149


1. 6 MgS04 720 100
15-20 .
2. 2 / 100
.
3. 46
, 4,89,6 /.
4. 24 .

4 20%
1/.
2. 10 50%
: (5 ) (
1,0 2% ).
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(, 1 /). ,
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. .
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4. 24 .
:
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24 ;
;

;
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46 ;
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, ;

150

( , ) ;
2,5-5,
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,
,
.
:
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2)
, ,
;,
3) ( ,
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;
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;
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. AT III

. AT III

() 1;
(PGIj) , .

, , , III , , , , ,
-.
, HELLP-
:
,
, , , ,
. ,
18%, 11%.
HELLP- 15%.
(, HELLP, )
16 50%,
40%. 16% / ,
.
,
. 1015%
.

HELLP .

[I. _________ 151

-, -,

, -1 (
), , , -2
( ).
.
/:

1) , III ;
2) ;
3) ;
4) ;
5) ;

6)
7)
8)
9)

+/-;
;
();
();

10) .
1.10.5. HELLP-

HELLP- (Hemolytic anemia Elevated Liver enzymes and Low Platelet


count - ,
) /; ,
. HELLP-
0,50,9% 1526%
/. 1-4%,
40%.
HELLP- : , , ,
( ), ,
. . ,
, ,
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.
,
. HELLP-
, , ,
.
.
HELLP- .
HELLP- ,
,
. .
.

152

1. HELLP- (,
, ) Weinstein 1982 .
.
2. , ,
, ,
.
:
; ;
; ; ;
.
3. HELLP- .
4. 0,5 0,9 %
15 26% .
1,0 4%, 40%.
5. HELLP- :
1) ;
2) ( , ,
, , , ,
);
3) : ,
, ,
, ;
4) - (
),
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1.6
HELLP-

,
,

6. HELLP-:
1)
,
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fjgga 1

153

2) -

(
) - (
,
, );
3)
,
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4)

(
);
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,
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^;
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-.
2) :
()
,
;
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HELLP- ,
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, ;

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;

PAI-1.

154


;
,
: I II
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;
.
, :
1) , ()
;
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;
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.
HELLP- -:
LLP- ,
, , ;
- 38% HELLP-;
, ,
,
- HELLP- 5%.
HELLP-:
;
;
(
).
HELLP-:
1)
;
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;
3)
70 /;
4)
40 . ;
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100%
, ;
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,
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, ;
7)
(4- 12- )
, .

1-

155


.
,
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.

1.10.6.
1. III
.
2. 30%, 50%.
3.
, ,
, VIII, V, AT III.
4.
,
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1.10.7.
1.

.
2.
,
.
.
3. :


, .
46 XX.
(69 XXY).

,
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90% .
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.
6.
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;

156

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;
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.
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.
9.


;

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1.11.


1. .

2.

.

1
3.

157

. -

500 ,
2000 .
4. I
:

+ (
, );
| ( ).
( 200 );
.
5002000
.

5. :

( 10002000 );
+
(, );
+ 4045%.
6. :
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.
7. 2025%
, 500 /.
.

.
8. ,
-
.
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.
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, III
.
11.
. ,

.
12.
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.
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13.
. , -

158

, .
Sheehan Murdoch 1938 .
.
.
.

.
.
14. ,
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.
15.
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,
.
, , , ,
, . ,

.
16.
1000-2000
.
17.
.
:
;
(5001500 );

.
2500 ( 600).
18. :
1) ;
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5) ;
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;

.
19.

.
,
.

f- 1.

159

, :
+ ;
I ;
+ , ;
+ .
800
2500 ,
.
20. , .

.

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21.
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22. 10% ,
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,
23 .
20% .
30% ,
.
:
1. (
) , .
, .
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,
.
.
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3.
. ,
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24- .

( ) .
1 .1 1 .1 . -

1.

.
. -

160


.
.
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.
3.
.
,
.
.

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.
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.

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5.
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.
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,

1.

___________ 161

,
, .
11.
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.
.
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.

.

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.
2. ,

-.
3. ,

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4. - ,

500,0 ( 1000,0 )
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.
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.
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.

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).

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. ,
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6 -

162

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.

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.

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X .

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.


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.
,

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- LeVeen-Denver .

.
,
LeVeen ,
.

163

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| .
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.
:
(t-PA)
1 (PAI-1).
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, ,


.

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.
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,
.
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.

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.

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164

. . VII X.

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V.

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.
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1.13. - .
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.
1865.

fjiQBd 1 __________ 165


1878 .

:
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;
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().

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,
[Falanga ., 2003].
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.


, [Rickies F.R. et al.,
2001].
.
.
, (),
.

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()

. , 1992 .
(Prandoni) . 250
,
() . ,
47 ,

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,
<
(
) |

166__________________ - ^

() CBDT
, [Barbui . et al. loooj
.


.

, , ,
[Prandoni P. et al., 1992].

[Falanga ., 1999].
.



, .

(V, VIII, IX, X),
-

:
8% 14%
( )
48% 36%
( )




, :
,
( F1+2,
, IX X, )

1.

167

+ ,
[
(), ()]
(-)

, ,
.

VII (FVIIa)
()
F1+2

(t-PA)
1 (1-1)

()
()

-

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4 (PF4)
\ (,)
-
CD62, CD63

(mTF)
s-

CD1 lb


t-PA
PAI-1
s-E-
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(TFPI)
,

. ,
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168

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.
5
.

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, [Falanga A. et al., 2003).
,
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, [tomeu .., 990].


,
,
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). (, ,
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.
.


:
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( , )
.



1.8.

fmamrn 1.

- 1 (- 1)
a (TN F-a)
(VEGF)
(FG F)

t-PA, u-PA, P A I-1, PAI-2, u-PAR





1.
,
:
;
.
:
V,
,
;
VIII,
.
,
VII (FVII/FVIIa). FVIIa
IX X.
, (..
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, (- 1, -, ).
,
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X FV1I.
, ,
.
2,

, (-),
(t-PA), PAI-1 PAI-2.

(u-PAR), .
.

,
[Kuenen B.C. et al., 2002]:

170

(T N F -a , I L - 10);
(VEGF, bF G F ).
,
. (
).
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.

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.
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4.

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.

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171


, , .
.
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, VEGF PDGF,
.
:

;
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;
(,
S);
.

( , ),
,
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.
1.9

.
1.9.

---------------------------

172

- 1




( .
, , ) [Verso . et al., 2003]

[Lee A.Y.Y. et al., 2003)

.

. 7 [Zacharski L.R. et al.
1998], (3 .).
.
,

.

1.14.

-

;
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,
.
,
II ,
, (, ,
, , .),

, , ( / II ). ,
, ,

.
.
:
1.
.
2. .
3.

.

1. ___________1 7 3


.

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.
(, , ),
,
.
,
: 1) ; 2) ; 3) (,
, ).
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.

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:
1) ;
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3) .


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174

,
, ^.
, .
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^
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.
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/
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. Bennett
-
. , c-fos
,
.
,
v-erb-B v-sis NIH3T3 . Regelson
,
. ,


.
.

, b-FG F .
,

, , ,
.
,
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(PMNS) , ,
.

2,
HL-60.
, ,
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,
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,
.

___________1 75

.



. 123 Maia ,
MRD .
,
.
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,
.

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,
.

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in vitro. -,

, ,

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PAI-1, , PCI

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in vitro,
u- ,
u-, .
,

176

,
.

(NK-).

.
() ,
.
,
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.

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.
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,

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,
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1. .
2. , ,
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3. .
4. .
5. .
6. .
7. .
1.10
.
,
4 5 , 15
. ,
().
, ,

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,
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177

f/eS
1.10.

*
PC PS, ,
APC-R

:
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L-
-

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(. 1.7,1.8).

, .
.



[Geerts et al., 2004].
:
1
.
,
.
,
. ,
5000 2
,
( 5000 ) [Bergqvist et al., 1995].


,

,

.

178

1.


-/


()

4300

3 ,6


(, )

4 500

3,8


()

5 000

2,7


()

3 90 0

3 ,5


()

450 0

1,9

(3-

1.8

()

-- --

1 2 0 0 0 -1 5 0 0 0

4 0 0 0 -6 5 0 0

4 0 -5 0
1 : 1

1 3 -2 2
2 : 1 4 :1

,

,
.
.
- ,
36 .

.
. ,
,

67%, 2
. - ,
, .

( ,
) .
:
.
. (1994),

1.

179

,
.
2
EN O XA CA N I ENOXACAN II.
[EN O XA C A N Study Group, 1997]
,
( ,
). 40
1 ,
. EN OXACAN II

( 28 ),
4 . 1 . [Bergqvist et al., 2002].
,
.
- L - , . ,

IL-lb , T F
T N F -a IL -lb . ,

[Vignoli et al., 2006].
, , ,
,
10-15%. 90-
,
, ,
. . 1.9
.
F A M O U S (Fragm in Advanced Malignancy Outcome Study):
1995 . -
, 374
, () 5000 M E
,

(. 1.10). ,
50% 35%
[ . ., Levine M .N ., 2004].
, 5%
( 15%).
C L O T (C om parison o f Low -M olecular-W eight Heparin vs Oral
Anticoagulant Therapy for the Prevention o f Recurrent Venous Throm boem bolism
in Patients with C ancer) [L ee A .Y .Y ., R ickies F .R ., 2003]:


6 . (. 1.11).

180

5 7 .
, 5 . 75% .

, 2 -3 .
, () 52%
.
, F D A
ASCO
( 6 ).

, .
,
, .
M ALT [Klerk .., 2003] 302 ,
6 . .

.
,
, -,
, - ,
.
: , , , .
, 20 078
. 2 :
2,5 1 /
. ,
-
, ,
.
,


,
. ,
, .
,
:
,

.



. , ,
( 50 .), ( 2 4 .),

1. _______ 181

1.9

Green

1992

21/67

31%

7/ 62

11%

Siraqusa

1995

23/ 81

28%

10/74

14%

Hettiarachchi

1999

71/323

22%

47/306

15%

Gould

1999

38/147

26%

22/132

17%

1.10
FAMOUS

190

, ./%
12 . 24 . 36 . 48 . 60 . 72 .
8 5 4 4 ,7 3 0 1 5 ,8 2 2 1 1 ,6 12 6 ,3
4 2 ,1
5
2 ,6

184

72

3 9 ,1

15

8 ,2

4 ,9

4 ,3

2 ,7

1,1

1.11
CLOT

60

, ./%
120
180
240
300

360

75

72

96

70

9 3 ,3

67

8 9 ,3 6 4 8 5 ,3 5 9 7 8 ,7 51

75

65

8 6 ,7

58

7 7 ,3

56

7 4 ,7 5 0 6 6 ,7 5 0 6 6 ,7 4 4 5 8 ,7

68

221

1 6 7 7 5 ,6

1 3 2 5 9 ,7 1 0 7 4 8 ,4 8 7 3 9 ,4 7 4 3 3 ,5 51 2 3 ,1

231

1 7 8 7 7 ,1

1 3 9 6 0 ,2 1 1 6 5 0 ,2 9 7

42

7 8 3 3 ,7 6 4 2 7 ,7


.

, 6 .,
6 . 6
, . C o licci

.

( ),
.

. ,
TF/FVII, , -

182

. , ,
2 -- .
,

.




.
,

,
.
,
, .
3400 ME .
, , ,
, .
,
.
,
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.
( 13 .)
,
,
,
.
.
,

- ( 2,5 ).
, ,
10 . ,
( 70% )
.
, ,
. ,
50%
, .

.
-

J H

183

, ,

.
, , ),
,
.
,
: 1) ; 2) ; 3) (,
, ).
,
, ,
,
, ,

.

( ).
, ,

,
,
.

, .
,
,

.



,
,

: 1) (
); 2) 3) .
, ,
:

,
.
-
, 3400 - M E,
5000 ME 3 ,
.
:

184


3 -6 . , '
3 -6 . 60-75%
.
--
0,1-0,5 /; .
0,6-1,0 / ( ) 1,0-2,0 /
( 2 ). -- 4
.
5000 2 ,
5000 3 .
1,5-2,5 -- 0,35-0,7 /
,
, . 1.12.
,
,
.

,
.

,
, .
, , ,
,
,
.
1-12
,



40
40
1/
2 /
5000
5000
1/
2 /
0,3
40-60 //
1/

3500 /

1750 /

1 / 2 / 1,5 /
1 /
200 / 1 / 100 /
2 / ( 180 /)
200 //
50
4100 ; 50-70 6150 ,
70 9200 2 /
( 17 /)
50-75 // 175 / 1 / (
18 000 /)
4200
45-69 4200
2 /
60 6300 2 /

jHH ________ 185



:
, - .
:

,
, ,

.
:
1.

,
(
. ).
2. : )
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-, .
,

.
, , ,

.
:

.

; ,
,
.

1.15.

.


,
. ,
,
, ,
,
[Satoshi
Gando, 2001].
.

186

- Muu,^

,
. .


.

, .
.
, 1988 .
, :

(. 1.13).
7
.
-1


[Levi . et al., 1993]. ,
,
,
[Gando S. et al., 2001]. ,

, .

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187
1.13

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188

et al., 1996; Yao Y.M. et al., 1998].



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.. , -.

// Materia Medica. 1997 1 (13).


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, , ,
.

( ).
0 85%.
, , .
. Zelger
3 : 1) ,
,
; 2)
,
; 3) ,
.
-
. ,
, .
, -,
.
. , ,
,
.
,
.


, ,
. -, ,

252


.
. -, ,
,
.
,
. -
(
).
,
. .

, , ,
.


. , -
. F-
. ,
.
,
. ,
,
.
2.4.2. -

-
, , , (. 2.8).
2,8

-










-

( )

253

, , .
JL ,
4 4 % .
4 8 % .


.
, , 10 60%
32
38%. 82%
.
,
.
, , :
, ,
, .

. .
.
,
.

- 1985 .
. ,
,
, .
10% .
,
.

91
14% . ,
,
.

: 1) ; 2)
; 3) ;
4) ( ,
); 5)
. ,
. ,
.

254



(. 2.9).
2.9
-
,

+/.

-
/
+

+/-
-


+
+
+
+
-


,

. , .
40 G P L
3 .

,
.
22% 26% .
6 % 10% .
, ,
.
-
.
. ,
.
, ,
.


,
35 44 , , 50 ,
.
, , , . -

7. ( )

255

4081
Vaarala . (1998) ,

.
() [Amergual .
etal., 1997]. .
,
.
,
.

.
, ,
. ,
,
.

5 15%.
,
IgG IgM
.
, , IgG
IgM,
.
,
:
1) 45 ;
2)
;
3)
, ;
4) , ,
, ;
5)
, .


. .
.
,
,
.

.

256

,
40% ,
4 -6 % .
,
, .
, , ,
-
.

2.4.3.
. 2.10.

2.10











( 1733% )
.
,
3
.
,
, .

.

.
.



3,5 1,8% .
25 ..

,
: -

257

^ 9. ( )

3)
,
(. 2.11).
? ().
,
, ,
;
.
,
: ( N 0 -1,
( V E G F ) ) , + - . ,
.
.
,
. ,
.
,

2.11


(
):

,
.
, ,
, ,
, ._____________________


( ):

,
,
_________

, , _______ _________





9 -

258

500
IgA,
IgG IgM.
12 .
, ,
IgG- J32-GP1,
. 216
10,6% ,
.
,
,
.
,
,
,
(FV Leiden, G2Q2.10A .).
,

.
-

- ()
, ,
, .

, .
,
.
, ,
,
.
. .
27 , 21
. 52%
,
.
.


.
,
, .
,
. , ,
.
,
, ,
.

2.4.4.

(. 2.12).
.
.

2.12



,

) _______________________________________________________


(livedo reticularis)
( 25% )
,
.
,
.
, ,
.
,
( Sneddon).

, ,
1963 . 5,5%
. , ,
, .
21 (30%)
10 (19%) - .

.
.
. (0,53 ) -

260

- ^

, ,
- .
. .
.
.
,
. ,
.


117 1
. .!
,
. ,
, ,
,
.


, 3,3%
19%
.
. ,
.
, .



/
. ,
. .

. ,
,
. ,
, , ,
.

. .

, .
.
.
, , .
,

.

2. ()

261


,
,
. .

, .

,
. 1965 .
.
Hughes
.
, , 85% .
( 14 )
.
.
57% , 28% , 21%
. , , , , .
2.4.5.


. - , ,
-, , , ,
.
, (
),
(. 2.13).
2.13


(
). //

,


( ,
) /
(
)
(
)


().
(, )

( ).
(
).
(
).

262


.
, ,

.
( / ),

,
.


.
.


.
, .
1988 . Kincaid-Smith
.
12 ( )
.

, .
.
, ,
:
, , , ,
,
, .
2 .4 .6 .


33 73%. ,
.
, ,
.

. 2.14.
2 .4 .7 .

,
,

2. ( ) __________

_______263
2.14


+ (amaurosis fugax)






/
+

4 /
t

.

.
:
1. 7%

, , ,

. .
2. (28%) ,
, .
.
3. (65%)
.
,
.
20% .

Pomeroy 1984 .
37-
, 7 .
,
, (1:40),
.
.
, ;
; , ;
. ,

.

,
. ,
, .

264

.
, IgG .
Young .
. Kinoshita
.
(
).
.
.
,
.
Kaushiket .,
215 42
1
,
.
.

.
. , (
). .
, .
.
,
, .
,
, .
.
48% .
-.
-
.
2.4.8.
:
, , ,
, ,
, (
2.2).


, :
10 .
( );
;

. ()____________

265

2.2.
I

II

III

<---------------------------------------------------------------- -------- ; -
, ,
;
4
, ,
.

.
.
[Cowchock S., 1997].

. Oshiro . . (1996)
366 2 ,
. 79
290 .
(> 80%). 50%
,
25%.
,
,
.
5075% [Khamashta .., 2006; ., 1999].
:
,
[ .., . ., 2003]. ,
[Geva . et al., 1994].

266

2 10%.
17 50%,
.
. 6%
.
. ,
,
(
) .
,
()
.
, ,
J2,8-30% .

(). S. Yasuda . (2000) 12%
2% .
.
Carmona Balasch 21,45%
.
,
.
.
6% .
.
,
,
.

2.5.
2 .5 .1 .
: ,
,

,
,
, .
,
,
.
, .

, , . ,
-

267

ritf ( )

- ,
^ .
, ( ) ^ (, , ) , , , .
, -
.

. 21-

- .
, .
,
, ,
- .

1 (PAI-1), (TF)
(t-PA -),
1. , , .

, . 1-1
TF( ),
,

(. 2.1). , ,
,
.

t-PA
u-



>

i t -
-

: ?
:

. 2.1.

268

- ^


-3 (IL-3) . IL-3 ~
, ,
(
, ).
, IL-3,
.
,
.
. V
, ,
.
,
:

;
;
;
,

(. 2.2).

.

. 2.2.

269

fjaBa2. ( )

d /beicru ,

, . ,

. ,
, ,


, .

, .
,
-.

, -,
(. 2.3).
, ,

() ,

,
.
;
- , .

(,
)


(,
,
)

^

/!

()
( . S h e e h a n , 1937 .)

N
-

. 2.3. :

270

2 .5 .2 .


, .
() ,
(), ,
( ), .
, , ,
, , , /
( ), ,
, .
. ,
10%,

[Bick R.L. et al., 2006].

, , , 20 70%.

( 12 .)
.
,
, .
, : , ,
.

2.5.2.1.
()

- : IgG, IgM IgA.
:
1.
2.
3. :

4.


, , , , .
, .


n Triple11- 1993). , * ,
\* , , ,
^ , 08(, .). ,
.
,
.
( ,
,
.
,
, ,
. 40%
95% .
:
, ,
.
,
, ,
. ,
() , ..
.
.

.
()
(), ,
20% .
.
() ()
() .

.
, , .
,
. .
.
.
-, .
. ,
,
. ,

272

, ,
.
.
. ,
.
,
, .
,
. . .
, , ,
,
.
90- ,

, , .
- : 2- I
(P2-GPI), , ,
, .
P2-GP1 , -
(. 2.15).

, . IgM.
,
() .
, ,
,
, .
, -, 2.15
:

Pj-GPI


S




XII
X
XI
VI l/Vlla

-
- 4-
_______

^|| _ ()

273

,
I ^, , - , XI.
*
n J9 7 2 . Feinstein Rapaport

,
. , ,
in vitro . ,
,
.
,
: ,
0 , , ,
.
Bowie 1963 ., 1973 . Nilsson ,
II III .

-GP1 IgG IgM . ,
,
,
. in
vilm ( ,
dR W T ) (. 2.4). , in vivo,
, , .

. ,
,
S, , (TFPI).

.
,
. ,
,
(dR W T ) [Miyakis S. et al., 2006].
P2-GP1 p 2- G P l
Pj-GPl 1961 . Schultze.

: ,
, , ( ). ,

, P2-GP1
. , P2-GP1
. ,
Pj-GPl ,

274

X)
-^.

. 2.4. 2- I
.
.

: ( ), S, (
), . TF
; PS S; ; ; PT

, (
-). 1968 .
P2GP1, . ,
.
1990 . p2-GPl ,
.
, p2-GPl
50 326 .
10 300 /.
1990 . Galli . , ,
, ,
, P2-GP1.
,
.
- P2-GP1
, , .
p2-GPl 14
. P2-GP1 5 ( )

()

275

60 ; ,
Lys317 Thr318. Cys281Cys288 . , 5,
, 4- P2
-GP1
, -2-1. , 5
4 ,

4.
, 4, , : , , 2 (
80% ). 5
. 4- 5-
,
4.
, , ,

-GP1. ,
- 2- 1 -, , ,
-2-1. ,
- . In vitro P2-GP1
- . -
, p2-GPl .
. -,
-GP1 ,
,
. -,
P 2- G P 1
.
P2-GP1 , aHTH-p2-G P l-
p2-GPl ,

(. 2.5).
, p2-GPl
2 p2-G P l , -
.
P2-GP1 , 100 .
P -GP1
( V) ,
-GP1 .
,
in vitro

in vitro.

276

~ - 2-
(32- 1

. 2.5. 2-

P2-GP1 , ..
P2-GP1, P2-GP1 ( ..),
ELISA- P2-GP1
.
, a h t h -P2-G P1 -
,
p2-GPl ,
.
,
P2-GP1 P2-GP1 V,
anoER .
, anoER
P2-GP1 P2-GP1
. AnoER
. ,
, P2-G P 1?
P2-GP1.
. ,
GP1 P2-GP1 ,
. ,
,
, .
, AnoER
.
P2-GP1 AnoER,
38, ^.
-Pj-G Pi. -2-1
,
. - P2-GP1
( , ).
-Pj-G Pl
. , -|32-1
(). -

H ffi ()

277

: P2-GP1, $ .(^, ,
^, ^. ,
,
. P2-GP1
Fcy-
. ,
v -Pj-GPl
( 38%),
.
-pj-GPl IgG IgM,
IgA [Cojocaru I.. et al., 2003]. ,
, , -2-1
IgG IgM -Pj-GPl IgA.

1 195 . Locliger , BA-
, .
.
BaS04 ,
BA-. ,
( )
, , 1990 . ,
,
P2-GP1.

5090% - .
,
. BA-,
, P2-GP1 -. ,
(
()2- ),

,
( V, II .).
, ,
. 1991 . . Bevers . ,
.
, X,
Va Villa
.
p.-G P l .
15% .
, ,
. ,

278

1 (
), -, 1 ( ),
,
, . ,
-/
. , N-
- - , S,
.
1980-
. , .
, , ,
. ,
,
.
, ,
.

. ,

. , ,

(. 2.6). , .
, J32-GP1
.
, .
,

. 2.6.

,[11< ()

279

, . *1^ 198
^. , p2-G P l
'?- .
L * P2-GP1 -
.
^ .
, **r -GP1 ELISA.
2
V
V. V ( -1,
)
vitrv,
|
.
( I)
( ). -
.
2 7 -,
. , 2 ,
70 .
.
:
- -, V ,

, II ,
.
V in vitro
.

.
, V
. , , ,
V
,
.
- ,
Rand ., V-.
V
,
.

(
)
. ,
, - ,

280

J32~GP1, ,
V , , ,
. V,

, ,

P2-G PI (Jacob .
et al., 1999]. ,
,
,
. -
V, ,
.

2.5.2.2.
(. 2.16).
,
. , BA-
( ),
I 2(P gI2) \ (^. ,
, . - -

, .

.

2.16
, -

/
TFPI


/, /, XII, ,
,
;
/


PAF

V, XI
P A I-I, PAI-2

TAFI

-1

N0

t-PA
-
u-RAR, ,
N0

0^

' ( )

281

- ,

- . ^ ,
^ . N. Del Papa
(1995) , 2-1-11 ,
-1, -6 1 , , .
, -
. ,
^.
. :
- 2-?1 - ,
,
? ,
. , - 2- 1 -
(), ( H U V E C ) [Meroni P.L. et al.,
2001]. , ft -GP1-AT , H U V E C ,
P2-GP1 . -j32-G P 1 -
HUVEC ,
- 6 .
.
-,
.
IgG
,
.
, , ,
, ,
.

,
, :
1.
, .
2. AT III. ,
, , p2-G P l ,
AT III.
3.
(TF) [Amengual .
et al., 1998]. P2-GP1
, ,
, .
,
,
.

282

4. .
5. .

(-
ICAM-1, VCAM-1), (TNF-a
IL-lb, IL-6). , ,
,
.
. ,
.
,
(PC).
,
-, (. 2.17).

PC. .
, , FVa FVIIIa
: . ,
, TAFI (- ) XIII , .
, ,
.
()
. PC , ,
.
2.17



(FV, VIII, VII, XI)


t-PA

N 0
FXIIIa




(TAFI)


()

283

.gig

1 , ^ [Ieko . et al.,
.

1999].

1
:
'
| ?|
1 ) , PC (
);
2) PC (
);
3) - ( -R),
:
PC
, ,
-,
Va V illa;
4) PC / PS ( PC/PS
).
, ,
.
.
(
, .)
.
, , , (32-G P l,
,
, .


FcyRII- F e-.
FcyR II-



^. \ , , ,
.

2.5.2.3.
, ,
.
,
.

.

284

, ,
,

.
1.

:
/ .
CD62p (-)
, in
vivo [Joseph J. et al., 1998].
,
. , .

;
,
, .
- , ,
.

.
( , /, ,
) (, ,
, )
, in vivo.
,
. -, . ,
()
,
, ,
, ,
.
(- ). ,

.
, - -. ,
, ,
, .

,
.
( )
.
-,
( , Va, ) -

()

__________________________ 285

.
, BA-)
.
, ,

, , ,
:
1) Fab-
( ,
) -
;
2) FcyRII;
3) , ,
,
, , , . ( ),
, -.
3 FcyR- (Rl, RII,
RIII), . FcyR-,
, FcyRII. Fey RII
, Fc-nop IgG, Fc- IgG
IgG, .
FcyRII - .
1 3 Ig .
p2-G Pl,
J. Amout
J. Vermilen. ,
,
, .
.
, ,
.
, ,
: , , -
II ( II).
FcyRII- Fc- ,

. FcyRII- Fc- : ,

.
FcyRII-
Fc- .
, (-
, .), , ,

286

. ,
PF4, -
(P2-G P I, , , )
.
(
, .)

- , , , 0,-G PJ,
,
, .


FcyRII- Fc-.
FcyRII-
-
:,

, (3), , , ,
. , ,
,
-
.
.
ADF ,

, PF4, -,
, , , , ,
.
,
,
.
, , ,
. ,


(5-9).
. , 5-9
. , , ,
,
, , . ,
FcyRII-
-
. , (,
).
, -

9 ()

Ijp f^

*~~

287

, . ,
^ ,
FcyRII ,
. 5-9
> , ,
.

,
. ,
* P2-G P l (
) , .
1994 . J. Arvieux . P2GP1 - ^ -p j-G 1- BA- ,
.
* ()
.
FcyR II- .
,
.
TF-
. FcyRII-,
,
. ,
, .. , 5
TF .
2.5.2.4.

.

,
.
, ,
,
.
, ,
, .
,
, ,
. , , 2 ,
.
. ( )
- .
,
: -

290

,
,
;

, , .
, V

.
,

: .
.

, . ,
,
.
,
- ,
, -
- . ,
,
, .
- ,
- .
.
-
, , ,
, , . ,
, ,
- .
, ,
:
-
,
.
2.5.2.3.


,
. .

, 30 .

.
(, ),

- ( )
(;

291

30 , , , -

2 ckv .

, .
.
,
5.

5-9,

.
1, C lq, C lr, Cls.

. C ls
4, 2
42. ,
-
,
.

.
.
.
(,
2). D
-, ().
, , , 5,
5, .
,
.
2-,

. 5 ,
,
. 5
C5aR.

,
. ,
, .. ,
, .
(DAF),

, (),
4. CD59 S
- , ,
, 1-, ( )
4- .

292



,
,
. -
,
DAF 4.

, [Kim Y.U. et al.,
1995]. / 100% .

, ,
.
,
IgG ,

[Girardi . et al., 2003]. ,

.

, : ,
[Holers V.M.
et al., 2002].
,
5
C5aR . ,
.
C5aR
[Girardi G. et al., 2003].

.
. 5
, , ,
, ,
, , . ,
5
.
, ,
(. 2.7).




. , 5

,
. C5aR [Kondo . et al., 2001]. 5

2. ( )
0

293

. 2.7.

PA I-1 , T N F -a ,

, , 5
. ,
.

. , 5
[Pierangel S.S. et al., 2003].
- G -
. ,
- ,
(, ),
- . ,
- CD59.
, CD59 ,
CD59
-
[Nangaku . et al., 1998].
,

294

.

, , .
.

2.S.2.6.
-
, ,
, .
,

(, , ,
.), (, ,
, , .), /
fgl 2 .

4 :
1. , :
) ()
;
) ,
,
(), .
2. ( ):
)
,
, - - ;
) - - (
, );
)
.

.
,
. , ,
-
2- (CD21), -
.
-
. -

|- 2.

()

295

.
4 -

HLA
1. HLA 1 -
> HLA II .
,
.
( ) ,
, .
,
, / .
.
,
,
.
- --.
, .
:

, . ,
,
.
1985 . Fujinam i Oldstone
.
,
.

CD 13 ( N).
CD13 - ,

.
CD13 .
2- HCV, HCV
450 (CYP) 2D6, 26 27
,
- - .

(), - (-) , .

, , .. .
, ,
,
( ).
, -

296

. , ,
, Fc- -.
, -
: ,
, , --
(TCR). -
. -
Fc- . -
Fc- .
,
( )

. ,
.

. , ,
, ,
-.
04- . -, C D 4 -
,
. -,
, CD4.

. -, ,
in vitro ,
. 08-
0 4 - . CDS ,
.
, ,
().
, ,
CD 8.
, ,
, -
HLA II
, -,
, Vp TCR. Vp,
1:10 - 100 .
-, ,
LA II . - ,
, HLA II . ,
CD4- 08- HLA II .
20 30 kDa ,
HLA- ,
.

2 ( )

297

- -

. - - (), -2.
-
-, LA 11
, ,
, ,
, ,
.
.
,
( ),
- ,
, , Mycoplasma arthritidis,
, , .

,
,
.
,
, , ,
.
C D4+, 08+-,
CD4+ .
CD4+ -
2 : , ,
- 1 (T h l),
- 2 (Th2). - ,
T h l, 12-,
ThO.
,
-.
- 2- ,
. T h l-
, - ( -), -2 -3 (-2, -3),
() (3 . 12- -3,
-4, -5, -6, -9, -10, -13, -14, -
( - ), - (). T h l-
2- : ,
T h l-, 12-, .
(
) (
).
T h l Th2 . T h l-
- (
, ,

296__________________ - *

. , ,
, Fc- -#
, - .
: ,
, , a/3--
(TCR). - .
. -
Fc- . -.
Fc- .
,
( )
. ,
.

. , ,
, ,
-.
04- . - , C D 4 -
,
. -,
, CD4. |

. -, ,
in vitro ,
. 08-
0 4 - . CDS ,
.
, ,
().
, ,
CD 8.
, ,
, -
HLA II
, -,
, Vp TCR. Vp,
1:10 - 100 .
-, ,
HLA II . - ,
, HLA II . ,
CD4- 08- HLA II .
20 30 kDa ,
HLA- ,
.

( )

297

1 - - - \|0 - (), - -2.


- -, HLA II
. , ,
, ,
, ,
.
.
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, , .

,
.
,
, , ,
.
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CD4+ .
CD4+ -
2 : , ,
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T h l, 2-,
ThO.
,
-.
Thl- 2- ,
. T h l-
, - ( -), -2 -3 (-2, -3),
( ) . 2- -3,
-4, -5, -6, -9, -10, -13, -14, -
( - ), - (). T h l-
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T h l-, 12-, .
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).
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, ,

298

1- ). IgE
2- .
(, )
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.
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- .
,
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.
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.
,
.

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- , - (ClfA).
. ,
.
, D.N. Eidhin . (1999),
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,
,
.

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.

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()

299

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, 70%
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.

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,
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300

, , V,
, S, .

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,
2-1, - 2-1 - (84 43-).
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.
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, ,
.
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,
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V BA-.
V,

. .

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S - .

,
.

,
(, )

()

301

, . 8 , , -

( )
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(, ) (, ) (IgG,
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,
. ,

, ,
, , . in vitro -
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.
G,
.

.
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.
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1CAM-1), -1 (vascular cell adhesion molecule-1
VCAM-1) -.
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.
:

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302

,
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.
.

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34 ,

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,

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,
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. -
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effector cell protease receptor 1). -


, .
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9 ( ) _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

303

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,
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. IgG
,
.
7.
. ,
12 ( PGI2) ,
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in vitro --1.
in vitro,
, ( 4, 1- ),
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, 3- 9- , .

Chlamydia
pneumoniae , ,
.
HSP60, - ,
.

.
, ,
.

, (),
.
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V, ,
, S, , , . ,
. ,
,
.

304


,
.
2 .5 .4 .

,
,
, .
,
,
,
.
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,
.


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,
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,
.

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.
.
.
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.
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?. ()

305

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1 . ,
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V:
+ V
;
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.
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.

.
, ,
.
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.
3 [Levy R.A. et al., 1998]:
1. -
.

306

/
.
,
.
,
.
,
.
, , .
2. , :
,

.
3. :
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),
,
.
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.
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.


( - , ,
, : V, , 2- 1
().
426 89 ,
. : 150
50 .
,
-,
.
,
( = 275): 47,1 %
54,4% .
, 82 (29,8%)
, 21 (7,6%) ( ) ,
140 (50,9% ) , 53 (19,3%)
, 54 (19,6%) , 32 (11,6%)

307

()

, 12 (4,3%)
.

275
:
I ( 82/29, 8 %) ,
57% .
II ( 110/40%) - ( 16 .)
' .

*^> 1 0 *^ 7 ^

'

III ( 30/10, 9%) , ( 16


22 .) .
IV ( 53/19, 3%) ,
.
I ( :=
=82/29,8%) 57% ( = 47)
25 (31%) . :
- (18%), 2 (2%), - 2-1 (4%), V 16
(20%), 2 (2%).
V I I ( 16 .) ( == 110/40%)
44 (40%) . :
- 19 (17,2%), 17 (15,4%), -pj-G P l 5 (21,8%),
V31 (28,1 %), .
I I I ( 16 22 .) ( =
= 30/10,9%) 11 (36,6%) .
: - 5 (16,6%), - 7 (23,3%), - 2-1 - 5(16,6%),
V 8 (26,6%)* 2 ( 6 ,6 %).
I V (
22 .) ( = 53/19,3%) 14 (26,4%)
. : 6 (11,3%), 7 (13,2%),
-Pj-G Pl 9 (16,9%), V 10 (18,6,%),
3 (5,6%).
( = 275) 94 (36,5%),
: 44 (16%), 33 (12%), -|3 2-1
23 (8,3%), V 65 (23,6%), 7 (2,5%).
( 89), ,
19 (21,3%)
:
(. 2.8, . . ).
:

.
.
V. ,
V
. ,
,
V.

308

2 .6 .

. ,
,
.

,
.
(),

(ELISA), IgG, IgM, IgA.
p2-G P l, -
, - 2-1-.
, - 2-1 ,
.
ELISA ( )
,
. , ,
, .
,
, , ,
. P2-GP1
.

P2-GP1.
IgG- IgM-.
mpl GPL. mpl
1 IgG.
( 60 mpl U/ml 80 GPL), (2080 GPL
2060 mpl U/ml) ( 20 G PL mpl U/ml).
10 GPL mpl U/ml .

IgG IgM 90%,
75%.
- , ,
.
, ,
, - 2-1 .
[Brandt et al., 1996]
(. 2.18).
.

()

309
2.18

.
( , ,
, .)
^ ,

(IgG, IgA, IgM)


BA(dRW T)

P2-GP1 (IgG, IgA, IgM)__________________

(IgG, IgA, IGM)


(IgG, IgA, IGM)
(IgG, IgA, IGM)
(IgG, IgA, IGM)
(IgG, IgA, IGM)

(
)

, 1990 .

.
; 1997 .

- ..
(. .. ).

(. 2.19).
2.19

1. -
.
:
()
(dPT)
(dRW T)
2.
,
.
3. ( )

.
, , :
|

.
,

:
,
( - ).

310

,
.
,
, *
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(dRWT) (. 2.9), .
-
,
, ,
/, ; -
.
,
-.
.
. ,
,
-.
,
( ).

,
.
(
, ) ,

FXII

>

FXIIa

FIX

. 2.9. (),

, .

0 ^2 ()

311


, .

, ,
,
. ,
:
. 3
, .

.
, ,
;
. ,
dRWT, .
dR W T,
2327 ,
, .

; IgG, IgM A. dR W T
.
()
.
.
dR W T ,
, . ,
dRWT ,
, . . IV
( ) , .
, (BioData Corporation)
100 / IV
. ,

, 9 / IV
, ,

dRWT . , ,
dR W T
,
, (Bell-Alton), IV
, .
, ,
,
, - 1 .,
,
2- () .

.

312


,
, P2-G Pl , , , , ELISA-
( ELISA).
(
, , - 2-1 ( ) .
, R. , 7% /
( 1), 15%
, ( 2), 15%
( 3) 22% 5.
,
.

(. 2 . 10, 2 . 11).

.
, :
1) :



/




2) d R W T :

V
V, X I

3) :






:


V
V, X I.

()

313

( )

()

( )


( )

( )

. 2.10.

dR W T

'


(V X )

( V)

( )

. 2.11.
(dR W T)

314

2-
.
;
. ,
,
4:1.
.
, , dRWT.

() 5 .
,

, . .
,
1:1. (
4 :1) , , , .. - , .
, 1 :1

( ) ( ).
, ..
()
-,
. ,
60 , 120 . ,
1520% .
2.20

F1 +2-



.

,
-.
-
.

- . -
.

D-

.
-,
.

()

~
..... -

.............

315

-

.

-, , (), F1+2 (. 2.20).
, ,

,
.

2.7.


, , ,
, .
.
; ,
, .
, .


. , (
, S) 20% , FV Leiden
20%, 25% , 14%,
, .. ,
80-90%
[Bick R.L. et al., 2006]. ,
,
.
.
, 26% (..
) 3040% ,
[Asherson R.A. et al., 2002].
,

.

, ,
, .
.
[Bick R.L. et al.,
2006]:
1. (, ).
2. ( ).

316

3. / .
4. .
5. ( , ,
).
6. .
,
.
2 .7 .1 .

,
,
.
, , .
. ,
10%,
[Bick R.L. et al., 2006].

.
().
, .

4 29% 14% (
2,02,85) 6 . ;
,
15% 6 % [Schulman S. et
al., 1998].
1029% [Galli . et al., 2003].


: 1) ;
2 )
; 3)
(- --, ).

.
1995 . . Khamashta .

( > 3,0).

( = 2,03,0).
. Khamashta . (1995) 6 147

()_________________________________ 317
0 0 53,
||jg Rosove P.M. Brewer (1992) 5 70 _ //(/ . , 0 )1 ,
* ( > 3 , 0 ) ,
( 0 , 0 1 5
. Khamashta; .. Rosove
).
1 , 3 ,
( 0 , 0 5 0 , 3 5 ).

( 6 1 0 0
). ,
( , ,
) , , ,
, .
, ;


. ,
3 , 0 2 , 0 , ..
.

,
. ,
, ,
, ,
, ,
, ( , ).

,
(2,03,0).
2,03,0 1,5%,
[Crowther . et al., 2003; Finazzi G. et al., 2005].
,
. , ,
2,03,0 3,14,0
2 [Fitzmaurice D.A. et al., 2002].
1%
. ,
,
.
, ,
2,03,0 [Crowther .. et al., 2005].

,
. ,

318


, .

.
. R. Derksen . (1993) ( = 2,54,0)
,
50% 2 , 8 75%.

.

.

.


, :
( 36 .
);
(> 40 GPL);
(
, , );
.

.
.
[Buller H.R. et al., 2004].

12 .
.

;
,
[Giron-Gonzalez J.A. et faff 2004].

,
:
?
;
, ?
,
?
(
D-, F1+2, )
. , 3 .
D- 96%
[Palareti G. et al., 2002].

( )

319

, 5 0 [Bick R.L. et al., 2006].


, ; . ,

. ,

.
,
, .
,
D -, F1+2, .
,
. ,
D-, F 1+2

[Cosmi . et al., 2005).

. ,
,
.
( ,

)
( > 3,0)
(, , ).
.
( , )
.
,

.
12 .
(. 2 . 21 ).
, ,
, .

(, ). ,
,

[Calvo-Alen et al., 2005].
, ,
,
. ,
,

320

2.2

11. 1

,

, (
)

2. ,
(81-325 /)
3. (
, )
4.
5.

6.

(, |2- ..)
.
.
, ,
, ,
,
,
.
, . ,

, ,
,
.
2 .7 .2 .


.
6 % [Lockshin M.D. et al., 2003]. R. . (2001)
20
, 15
2,2 , 20 1,5 ;
1,8 1,5 .



.
WARSS APASS 2
(325 /)

()

321

( 2,2)
^ ,
( 10%) [Redman A.R.,
Allen L.C., 2002]. . Ta
il ,, ,
, (325 /)
( = 2,0)
.
, ,
. ,
WARSS APASS 63 ;
,
, ..
, . ,

. ,

.
, , WARSS APASS
" [RuizIrastorza G. et al., 2005].
: , , ,
. , ,
,
[Ruiz-Irastorza G.'et al., 2005].

( + ).

( = 2,0-3,0)
(325 /) [van Es R.F. et al., 2002].

: , , , , .
,
.
,
.
, , ,
.

. 2 .22 .
2.7.3.


(3,04,0)
()
II -

322

-
2.22

2 ,0 -3 ,0

(!)
12 .
12 ., ,
, ,
, ,
(D- , F1+2, ).
1.

|




(81-150 /)
( > 3)

-
,


( > 3)+/- ,
2.

325 /
(2 ,2 )

( = 2 ,0 -3 ,0 ) +
, (1 6 0 -3 2 5 /)
,
,
,


( = 2 ,0 -3 ,0 ) +
160 -3 2 5 /)
I ( = 2 ,0 -3 ,0 ) +

I 81 /)
5
( > 3) ,

(2,0-3,0),

M.R. Khamashta . (1995) .. Rosove
. (1992), ,
20 %,
5%.
,
2,03,0
1,5%, [Crowther .. et

()

----- -

323

* Finazzi G. et al., 2005]. ,


| .
, , ^ 2,03,0 [Crowther .. et al., 2005].
0 . ,

^ .
.

! 50-65% :
, ,
(, ,
, , ),
( , ).
,
( ,
, ), ,
.
, , , , .
,
, ,
.
,
. ,
.

(81325 /)
( = 3,0-4,0) (
4,0-5,0) .
,
, ,
(
),
.

, .

[Dentali F. et al., 2005].

.
[Petri .,
1998]. ,
[Edwards .. et al., 1997].

().

324


I Branch D. W. et al., 2000J .
.

0,4 / 25 .
.
, .
.
23 3 .
.
, ,
. ,
(Asherson R.A. et al.,
2002]. ,
.
.

[Asherson R.A. et
., 1998].
, -
,

.
,
, .
, . . -,
, .

.
-p.-GPl
[Meroni R.L. et ., 200 JJ. ,
,
.
, .
.

(,
, , ).
,

,
.

, ,
.

.

- ()

325

0----- ft -

. 2.23.
2.23

1. :

.
2. , .
3. :
( , ,
, ,
)
( FV Leiden,
G20210A,
PAI-1, t-PA, , S .)
( MTHFR 677)

[
(
( 4 ,0 -5 ,0 )
( = 3 ,0 -4 ,0
= 4 ,0 -5 ,0 ) +

(8 1 -3 2 5 /)


*
*
*

*
*

,

0 ,4 // 2 - 5

.



.

.

- +
+

,
.

326

-
. 2.23

I

I

1. ( 2,0-3,0)
2. 1
; !!

(D-, , +2)
( ,
, )
,
** !

* ( = 3,0-4,0).
** .

2.7.4.


, , , , .
,
,
,
.
15%, 2530%, 3540%
[Hatasaka .., 1994].
1015% [Asherson R.A. et al., 2002].
,

, .
,
.
2.7.4.1.



.
( 40 / ) 20
,
[Lubbe W.F. et al., 1983].
75 /
\ .
6 ,
.
5 .

- . ()

---------------

327

, .
30 5 80 /.
, 250-300 /.
65-70% [Asherson R.A.
5 ,2 0 0 2 ] .
w
1989 . . Lockshin . -

. ,
,
^ , . , 65% [Cowchock S.
etal., 1996];
, ,
, , .
, ,
, .

.

.
,
, ,
.
-- .

, , ,
, , -
(
).
, , .
, ,
. :
. ,

, .

, ,
(0,3-0 ,8 /)
II .


(40 /)
(20 000 /) [Cowchock S. et al.,
1992], (20 /) -

328

[Silver R.K. et al., 1993], (0,50,8 //cyr)


+ [Laskin .A. et al., 1997].
, ,
, ,
.
,
.
.

-1,
,
^ (PGI2) .
1 (-1)

( 10 ),
, , ,
, . , , . -,
, ,
.

,
, ,
(
, , ,
- .).
,
.

- ,
.

,
, ,
.
, BMS,
^
, ,
[Shoenfeld Y. et al., 2001].
, IL-3
. IL-3 - (-)
.
IL-3
[Fishman P. et al., 1993].
,

()

329

IL-3 - [Blank .
. J998] , ; .
, IL-3.
,
1L-3. ,
,
' [Bose .
etal 2005].
.


70% [Balasch J. et al., 1993; Silver R.K. et al., 1993].

, ,
: , , ,
.
42 100% [Asherson R.A. et al., 2002].
, . .
, ,
, ,
.
,
. ,
W.Kutteh (1996) 44% ,
, 80%
.
, (7581 /),
(, ,
),

, , , ,
, 90% [ .., 2003].
.

(81 /) ,
.
, 351 , 8 %
. 100%
[Bick R.L. et al., 2006].

75-100 /. ; ,
, , 75 /
. -
II III 150 / [Ginsberg J.S.
etal., 1998]. I 111

330

. III
(
),
,
. ,
, II III

- [Grab D., 2000].

36 . .

.

(75-81 /), , II
III . ,
,
.
,
.


.
, ,
,

, (
5081 /)
. 90-

(60100 /)
7075% [Kutteh W.H., 1996; Backos . et al., 1999].

[Kutteh W.H.,
1996].

: , ,
.

,
, - ().

,
, . 1-2%
, ,
( 15 000 /).
. 5%

()

331

9 6 12 . [ R.L. et al.,

,
(1 ,5 0 0 /
*) D,
. . , , .
( ( 0 , 1 - 1 % )

Skentin .. et al., 2 0 0 4 ] .

( ).
:

,


.
+ .
I .
+
.
* 12
.
-
( 0,1%), . .
IV .

| .

[Noble L.S. et al., 2005].

,

, .
,
, -;
, ;
,

.


.
, , , ,
,
I ,
,
.

332

, ,
, , ,
,
, , (
)
--
(
;

, ,
). ,
-- . ,
-
79 , .
,

. . ,

.
,
,
. , ,

,
, , .
,
6- 12- .

.
,
, .
, ,
, , , ,
. ,
, 5 . ;
6- 12- ;
, ,
12- 3536- ,
.
,
,
,
, ,
.
, , -

^ ()

333

(, )
.
, (
, ).

.


(). 1985 . . McVerrry .
^
.
, , , ,
, , .
, , .
- ,

F(ab)2 ,
[Caccavo D. et al., 1994].

,
. ,
-
-. ,
, - ,
, .
Pierangeli S. . (2001)
- ,
.
,
, ?

?
. Galli . (1991),
,
in vivo,
in vitro. .
, ,
, ,
[Krause I. et al.,
1998]. ,
. ,
Sherer Y. . (2001)

334

(), P2-GP1, , ,
.

(, , )
.

D. Branch . 2000 .

(1 / 2
1 ) ,
, ,
().
12 5
10
5 [ H.J. et al., 1996].
. Marzusch . (1996): 38
I
81,4% .
.

:

17%, +
+ 41%
[Sher G. et al., 1998].
,
,

. 400 // 5 1
1 // 2 1 , I
II ,
,
70100% (
: , ) [Harris E.N. et al., 1998].
,
( 76 78%
), ( ,
) , (14% 5% ) [Vaquero . et al., 2001].
,
, .

(84%)
(57%) 3
[Triolo G. et al., 2003].

( )

335

,
, . . .


IgG , .

.
,
. ,
,
.

.


, :
, ,
,
, ,
, V
[Di Sim oni N . et al., 2000].

.

.
, ( 13 ).
,
, .

23 12 .
-
, . . .
, ,
28-30 . ,
, , -, [ .. ., 2005].
,
, ,
,
.

23 2 ,
17- 10 . -

336

- /lnuifn

.
,
12 . .
,
,
, 2830 . ,
,
,
, , .
, ,

,
[ .. ., 2005].

()
.
() , ,
.
, , ,
, ,
, , , (IL-6,
CD8 IL-2) [Wallace D.J. et al., 1993; T am L.S. et al., 2000].

:
, ,
[Edwards .. et al., 1997]. in
vitro ,
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.
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100 000/
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> 4 /

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1
1

0
1
2
2
2

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5.

, - ______________________ 373

,
0 .
0 . Karmochkine . (1996), 33% .
- ,
. ,
-
.

, .
C.S. Kitchens (1998),
, .

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: S (PC, PS), III (AT III),
, , -,
(. 3.1).
. Amital . (2001), 2
, ,
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.
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,
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, , ,
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TF

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374

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1



-1
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,

. ,


,
.

.
N. Del Papa . (1992), , ,
,
() -
. , P.L. Meroni . (2004), -

pjflgfl - , -

375

, ,
| 0 ,
(HUVEC).

.
24 200 ,
()* ,
.
,
.
,
, ,
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, .
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.
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,
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, -2-1.
5- V
t-PA. ,
- 2- 1, .

, (-, ICAM-1, VCAM-1), (TNF-a,
IL-lb, IL-6). , , ,

. R. Simantov . (1995), HUVEC
23 .

S. Pierangeli . (1997),
,
, .
,
. ,

ICAM-1 VCAM-1,
.
in vivo
. ,

. ,

, - _______________________377

. PG I 2 , , ,
,
N . Del Papa . (1997)
^ 6--PGF1
Jfrti aHTH-(32-G P l
H U V E C . -- P G F la

,
.

. . A t s u m i . (1998)
in vitro -1
- 2- 1 .
ET- .
,
.
, -1 . -1
, , .

N 0 ,
NO- ( i N O S ) ,
.
, ,
. , N 0
.

,
[ .., 2004].
,

,
.
,
.
3.1.4.3.


.
, ,
, , a trm -P 2-G P l,
, .
. , A. Bordron .
(1998), ()
.

378


. .

,
.
- - .
,
.
V, ,
,
.
V,
,
.
, V , , ,
. ,
V . ,
, .
.
,
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; 2 ) ,
.
N. Nakamura . (1994) ,
HUVEC.
. , D. M itra .
(1998),
-
-1 -3.
3.1.4.4.


,
.
CD4+ -,
- 1 (),
1L-2, IFN-y
, 2 (Th2), IL-4, IL -5, IL- 6 , IL-9,
IL-10 .
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( , 1), a T h 2 -
. -

- , -

379

* T hl, Th2. , .
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, TN F-a, IL- 6 , IL-1,
: ,
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,
.
, . ,

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IL-18,
.
,
( ,
, )
. , G. Girardi . (2003)
,
5, ,
.
Thl- 12-. ,
Th2,
Thl- (T N F -a, 1L-Ib, IL- 6 )
.
, , ,
, . 20%
.
J. Berman . (2005) T N F -a

. , IgG

TNF-a, ,
, .

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- .
T N F -a 1,

, ,
.
. ,
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5 5
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,
,

380


. -
,
,
.

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. IL-3 GM -CSF
, . , IL-3

.
. P. Fishman . (1995),
IL-3
. ,
, .
-1, ^
,
, , IL-3.
. ,
(7581 /)
. , ,
IL-3. ,
.
,

,
( , ).
, R. Bulla . (1999),

in vitro.
3.1.4.5.
.

,
G. . (1999).
3 . , Salmonella typhi,
. , S. typhi
.
,
-, |32-GP1.
,
, P2-GP1.

aHTH-p2- G P l - . ,
(
HLA)
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, -

if

381

-,

p 2- G P l .

.
,
-, , , aKJI
. , 1
.
, , ,

.
I Zhang . (1999) Sbi Staphylococcus
aureus, p2-G Pl.
. . Gharavi
. (1999). 7 ,
, , GDKU1- &1 -.
IX) P2-GP1. . . Gharavi .,
, -
.GP1 , -GP1 . ,
.
. Blank (2002)
(TLRVYK), p 2-G P l,
-3.
TLRVYK
.

. , , TLRVYK-co , - 2- 1-.
,
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: , , .
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, ,

, .

Thl- (T N F -a, 1L-Ib, IFN-y),
. ,
, 1L-1,
. T F
, -

376

. ,

.
, , , .

. , t-PA
;
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[Combes V.
et al., 1999]. in vivo
in vitro, ,

.
, , ,
,
,
.
.
, - 2-1-,
, (T N F-a, IL-1) ,

NF-kB. , ,
P2-GP1, ,
Toll/IL- -, [Rashi . et al., 2003]. , , , ,
- 2-1. , N. Del Papa . (1997), IL-lb,
, HUVEC,
IL-1 (IL-IRa) ,
, - 2-0 1 -.
NF-kB TF
, . ,
T F TFPI .

^/ (T X A ^ P G y .

L.O. Carreras (1982).

. ,
TXA^/PG^
^. A. Habib . (1991)
2 (-2) H U V EC
.
11 --2,

382

- /

. -,
,
TF . , aKJI
, Fc-.
, ,
aKJI, ,
. ,

.
, ,
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, ,
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.

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, .
PC, .
,
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PC,
.

, -

383
3.5


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PC
. ,



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TF, vWF , .
, ,
PC,
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[Asherson R.A. et al., 2002].
3.1.4.7.

,
,
. -

384

,
.
.

(
/ ).
CD62p (-)
,
.
J. Amout J. Vermilen,
,
, ,

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. , .

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- ,
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.
, , ,
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, , , . , ,
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Fc- IgG IgG,
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.
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385

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(5-9).

. , FcyRII - .
5-9 ,
.

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-p j-G P l BA- ,
.
FcyRII .

386

,
.
TF-
. FcyRII, ,

. , ,
, . . , 5 .

. ,

.
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NF-kB , TF. . , TFVila
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.
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. ,
,
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, :
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,
(
), - (), HELLP- - () (. 3.6).
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.
, , , ,
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387

, -

3.6
,

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388


(), vWF.
vWF . ,
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, ,
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, ,
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:
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.
3 .1 .6 .

,
.

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.
.

.
. ,

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.
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389

-.
130 ,

[Asherson R.A. et al., 2003].
,
. ,
,
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.
X . (, ,
, 2002 .)
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, - /).
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390


.
, ,
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, /
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. 3.8.

.
. . Amital . (2001), (
) .
1 . AT III,
, X IX.

II.
AT III X
.
, ,
, ,
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/ 7 -1 0
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100-275 // 3 .

3. , -

391


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; )
, . . ()
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--
. , 30%
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,
TFPI. T F
-
, , - ,
.

, ,
, - . ,
D. . (1997),
,

TN F-a.
.

.
, .. Weyand .
(1997),

NF-kB,
. ,
.


, - , ,
IgG
,
.

. IgA,
.

, . .
.
65 , , . ,
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.

392


, , , ,
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,
, .
,

. ,
. G. Espinosa . (2004)
46
. 26% -
, 23% , 15%
, 13%, 13% HELLP 4%. 34%
70% .

-
( ).
,
, .

, AT III PC.
R. Flamholz . (1999), - 2-1-
.
IgA- .
, AT III
PC. , () ( -), (
NF-kB,

) [Opal S.M. et al., 2003].
PROWESS
[Bernard G.R. et al., 2001]. (< 80%)
.
,
.
, ,
, , , , ,
.

,
,
.
(5 //
7 ) [Kane D. et al., 1998].
,

3. , -

393

,
[Zwissler . et al., 1 9 9 6 ] .

.

,
, ,
, .
-

/ ,
80 (Asherson R.A. et al.,
2001].

(Malayan pit).
,
. ,
-,
, ,

.
[D osekun . . et al., 1984]. .

, 1 2 . ,
:
1) P G I 2 P G E 2;
2) 4 (LTB4), ;
3) 1-1
t-PA ;
4) -1;
5)
.
,
, T N F -a
,
. ,
TNF-a
IgG IgM . ,
,
.
,

,
. , A. Burcoglu-O'Ral
. (2002), 25 ,
,

394

, PAI-1
TNF-a, -1,
.
(,
) , , , -TNF-a-
.
D. . (2003), TN F-a
, .
CD-20 [Rubenstein . et al., 2006J. ,
,
.

(, , , , , ),
. ,

.
,

.
, ,
,
, ,

. ,
,
,
. ,
, -
2-
.
3 .1 .7 .

3., 24 , 20.03.05 . :
2728 .; ; ();
.
. 4
25 .
.
, .
.
, 20.03
.
25.03
16.00 .
. 120/80 .. 88 ./.
. . ,
.

Iffpan3. , -

3 95

: 27 .; ;
; ; ,
; . :
136 /, Ht 40%, 78,7 /, 1,97 /.

,
24 .
26.03 18.00 . 190/110
.., 110 ./, 24 . :
900,0 , 500,0
(), .
( 980,0 , 34 ).
, .
, , , , , , , ,
, .
27.03 20.00 ,
26-28 , . ,
.
. ,
, - ,
- .
28.03 130/80 .., 80-100 ./, 200-250 ..,
, .
. 100 .
4 4 . :
, .
29.03 ,
, ,
1,52 .
30.03 . 110/70
.., 90100 ./, , 400 ..
31.03 ( 5- ), ,
, , ,
. , , .
, , .
. 120/80 .. 100 ./, 18 .
1.04 , . 130/80 ..,
84-90 ./, , . :
1,65 /, 56 ./., . : 68 /, Ht
20%, 13,8*109/ , 156*109/, 60 /.
: 73 /, 7,4/, 4,4 /,
37 /. : 27 , 75%, 2,44 /.
: 1) IgM-, IgG-;
2) , IgM-, IgG-;
3) IgM-, IgG-;
4) IgM-, IgG-.
:
G20210A, MTHFRC677T, FV Leiden .
2.04
,
(), , ,

396

. . 120/80 ..
9- , . 10- .
12.04 .

,
.
, ,
- .

,
,
, .

.
,
,
.

., 23 , 19.05.05 .
12 .
, ,
. 2003 .
, , ; 2003 .
, , , .
: .

, IgG
P2-GP1 (90 / 10 /).
, ,
( aHTH-p2-G P I ) : .
.
2004 .
, . ,
.
. , ,
. , ,
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,

, ,
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.
.
( 1 .)
.
30 /
, 2 - 500
3 800 . :
, 60 / 6 .
23.

3. , -

397

, . .
.
, .
,
.
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.
.
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Kfc-GPl 16 /. ,
30 / 15 /.
FV Leiden
G20210A .
MTHFR 677,
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PAI-1 (675 4G/5G), (455G/A) XII,
Gp-IMa (1565 /).
: 12 . (

), (
), .
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-. 60 /,
90 /.
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- 1,5 /.
. ,
.
.
, . 40-
Joel-Cohen.
, 600 . 3050 ,
50 , 9 . 2
60 /. 24 .
3 30 /.
2 30 /
60 / 2 .

1.
,
.
: , - ( FXII),
t-PA
PAI-1 675 4G/5G
PAI-1.

. -

398

, ,
.
.

.

. , ,

,
[Makatsariya A. et al. 2006].
R.A. Asherson, 2005 . ()
PC
[Katzav A. et al., 2005]. ,

.
,
, ,
, 1520%. ,


.
, ,

(, ,
, )
.

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-
.
. .
3.

.
.
4.
. ,
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399

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,
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. ,

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.
,
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400

. ,


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,

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. ,
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,
.
,

.
5.

.

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.
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.
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.
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6 . ,
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- .
,
.
,
.
,
, HELLP-, -,

. , - ______________________ 401

,
.
,
,
.
.
,
.
3.1.8.


.
(, , )
. D. Erkan . (2003), 40%
.

,
.

D. Erkan . (2002). :
. :

;
100 000/
;
.
2. :
;

.
3. :
,
;


, ,
,
;
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.

, , .
()
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6 . .
, .

402

,
, .
,
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,
.
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. D. . (2003), 66 % ,
,
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, .
25%. ,
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5 .
.

.
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,

. > 4
,
.

. ,
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.
, .
, , ,
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;
;
,

TGF-P;

f- , -

403

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- .
,
.

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, (-1, -)
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:
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-1. Minori . (2001),

- 2-1-.
,
(
,
).
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,
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. ,
.

. ,
,
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.
,
. ,
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. ,
,

.
, ,
, -, ,
, , HELLP-, ..
.

.

404


.

,
, .
,
,
.
XVI . .
, .
, XX .

(). , 80- XX .,
.
, ,
.
.
3 .2 . -
()
3 .2 .1 .

- ,
,
/ . ,
, World Health Organization
(1997)
, ,
, ,
, , , .
, - ,
:
1)
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2) (), .
; ,
,
,
, ,
.
,
- , ,
, ( )
.
,
, ,

3. , -

405

, -,
, .
3.2.2.

1957 . V
- Rodger . Weismann, 43- ,
D a rtm o u th Medical School, Richard W. Tobin 3-
10
Hitchcock Memorial Hospital (, -).
, , -
, .
, ; .
, -

. ,
- .
R.E. Weismann R.W. Tobin,
715- .
9 , 6
, 2 .

, ,
.
,
.
, ,
- . ,
, . .
.
, R.E. Weismann R.W. Tobin
: , ,
,
.
R.E. Weismann R.W. Tobin
,
.
Brook Roberts

,
. 9
11 . 10
. . Roberts
:
. . -

406


.
. Roberts
- , ,
. , ,
.
. Roberts . ,
, ,
-
.

,
.
1970 .
. 1969 . 78-
() Natelson .
10- . ,
,
. , , -
( <0,5 /, /),
,
. ,
in vitro
. -
.
, ,
D. Silver G.R. Rhodes
R.H. Dixon. , ,
. ,
D. Silver ., (8 106/ 10 106/
) , .
,
1 .
.
.
-, ,
,
.
-,
, : (
)
.
-, IgG
,
, - IgG-.

, -
-------------------------:--------------------------------

407

1977 . G.R. Rhodes . ,


. ,
,
.

. 1975 . Fratantoni .
(4 106) ,
. . In v/Yro- ,
,
.
, , , ,
.
5 , 8
, , ,
. Babcock . (1976) ,
, .
,
, ,
5- , .
1979 . Jonatan Tonn . ,
.
.
, ,
phlegmasia cerulea doleus, ,
2 (
, ).
, -
() , , , ,
-
, ,
( , , ).
1980 . Bell Royall ,
(26%) ,
( ), (8 %), (
).
,
52 . - Bell
,
. , ,

.

, . . - -

408



.


.
Beng Chong (1981) Lancet
.
1989 . Platelet Immunobiologi Workshop
.
I,
II.
, , .

.

. ,
, ,
,
.
1983 .
John Kelton Dave Sheridan
, , ,
,
- (
). ,
(SRA platelet serotonin release assay),
, Fraser
Mustard . ,
(
) , -

. , ,
, ().

.
Sheridan . :
-
(0,051 /),
(10100 /) ,
, ,
, , (
two - ).
Greinacher . (1994) ,
PF4
PF4, . , ,
-

,. , -

409

-. , , , ,


.
1992 . Jean Amiral, Dominique ,
, , -,
4- - .
, ,
,
-.

J.G. Kelton . (2005)
Fc-
.

, , 1982 .,
,
.
1982 . Job Harenberg

48- ,

. 6
, .

.
II
.
(hirudo
medicinalis) . ,
. XX .

. ,
.
Haas JustusLiebig ()
.
.

.
1956 . F. Markwardt Ernst-Moritz-Arndt

.
Andreas Greinacher
11
.
II (1997), (1998).

410


II , .
, - .
II
- II
.
II ,
,
,
.
,
II.
3 .2 .3 . .


, , .

, vWF.
- ,
,
PF4.
.
II 15%. ,
, 1% , ,
0,1-1 % , , , 0,1 %
[Warkentin .. et al., 2004]. -
(35-65%
),
.
(13%).
, 1 .
, .

,
, ,
.

, . ,
1167 [Sanson B.J. et al., 1999].
,
, .

: 3570%
, 20 % -

, -

411

, 30%
fWarkentin .. et al., 2005].

,
. ,
, ,

.

.
,
,
- . ,

.
-
.
:
+ I () .
+ II () .
I
1. ,
.
2. : 1030%
.
3. .
4. : -
. ,
.
5. : .
6. II, , .
7. I, ,
. , in
vitro .
, in vivo

.
II
II
( 414- ), ,
.

II:

1. , ,
4 - 14- ( 10- ).
2. 3060 .,
5 . 1 ;
50% .

412

3. 30 9/
II .
//(. 3.9):
) II :

() ;
,
;
, ;
, ,
.
II :
,
( (3 /),
(500 /),
);
, , , ,
[Locke C.F.S. et al., 2005];
) ( 24 )
, (
100 )
;
) ,
( , );
)
, ,
.
, ,
. II

, ,
.
- ,
, :
1) ,
;
3.9

( .. W arkentin ., 2005)

>

1 0 -4 0

(1 0 -1 4 < 4 )

5 -1 0
3 -5

>

( > )

1 ,5 -2

flflpafl- , -

413

2) (

50% )
;
3)
;
4)
.
, ,
: , , ,
. ,
, .
, . . .
,
, .

.
,

. J. Amout (1996),
, Ig-
(. 3.10).


.

II
(. 3.11).
, ,
. ,

, ,
. ,
, , .
50%
.
.
, (,
, , ,
). ,
,
.
, .
,
10*109/.
in vivo . , -

414

-
3.10


(+/-)

>
>
, ,
, ,



1. 1. ( -
)
:
(HIPA, )
1.
2. PF4- 2.
Ahth-J32-GP1
(
()
)

2.


()

;


Fc- ;

( Fc-pe
)

,
.

,
, .
, . ,
,
, : <
< ( ) <
.

.
. 50% .
.. Warkentin (1998),
. , ,
,
.
,
(> 95%) .

. , - _________________

415

3.11
II

() ,
; , ,
(50% ), (25%).
,
(10% ).
,

, (3%).
:
, (< 3%)
4 , .

( )
(5 -1 0 % ).
(3-5% ), (3-5% ).
:
, ,
, (< 3%)
(in situ/ )

, , ,

(5 -1 0 %
II, ),

( -,
,
,

) (< 3% )
(5 -1 0 % )

: , , .
5 -3 0 : , , ,
, .
: ,
(- .
)
: .

5% .
,
. ( 86 %) ,
, ,
. -

416

() ,
.
.
( ,
) ,
. : )
( )) , ) , , 4.

Towne . 1979 . ,
phlegmasia cerulea dolorens (
).
, .
,

, .
( )
PC.
48120 , -- PC PS/.. .
PC ( VII).

PC (,
FV Leiden ).

5 20% [Warkentin .. et al., 2004].

,
.
,
-
(, , ).

,
,
.
,
,
(, , , ).
-
,
, (, ),
()

.
, -
fnABa

417

- 100 109/ (

150X109/).

, ,

, , ,
, ,
. . .

, ,
.
,

.

. ,
.

.

.
, .

-,
( )
.
,
, , 510%.

(PC, 111 )
. -

.
,
.

[Weismann, Tobin et al., 1958].
,
:
,
->
.
,
,
.
,
, , ,
14 -

418

, .
530
. .
, . .
. ,
,
.
, . .
.

.

( , -,
, , )
.
, , ,
. ,
, ,
.
, -.
,
, , .
,
, .
, 1020% - .
, 15% -
,
. ,
, . ,
.
(),
. ,

.
-
( ) ,
,
. ,
(). -
(CD4+) ,
. 04-
,
.

.

, - _________________ 419

-. , ij -
(

)- -
( ),
.
, ,
, 3- ,
30% ,

, ;
.
(livedo
reticularis), ,
. Livedo reticularis

.

. ,

.
, .
(,
).
, , ,
(
, , ,
.).
. , ,
.
- ,
-, ,
, , .
,
,
, , , .
, - , .

(), .
,
:
-.
- .
.

420

.
/.
.
(, ,
..).
.
.
, .
,
.
.
1. , (
510-
),
( 1- ).
2.
(414 )
.
3.
( 24 ) ,
(
100 ).
, , 5080 (
). ,
, ,

5 , .. ,
.
4. ( 35% )
.
,
in vitro .
5. 50%
514-

, 150*109/.
6.
,
.
7. ,
.
8.
, , ,
, , .
9. ,
,

|1. , -

421

,
( )
(, , .).
.

- (
-).
, ,
.
. ,
, 530
,
,
.
,
,
.
3.2.4.


II 1973 . ,
IgG 2 II
. ,
,
( ),
.
, ,
, ,
, , ^
.
. ,
IgG - ,
.

. FcyRII (CD32 ).
, ,
Fc- IgG,
IgG- IgG,
. FcyRII
, 2 .
, , , IgGr
, FcyRII
.
FcyRII . ,
, FcyRII ,
, II.

422


:
)
II;
) ,
,
II.
, ,
GPlb-IX, , ,
FcyRII PF4
.
GPlb-IX FcyRII .
, , *
FcyRII, GPlb-IX.
,
II.
PF4;
PF4. .
FcyRII
4, , , .

PF4
[Rauva et al., 2005]. , FcyRII
, .
II
, 510%
-.
II ,
. , ,
PF4.
( ),
, PF4 . PF4 II.
, ,
.

. ,
TF .
,
.

, . , PF4
, , .

3- , -

423

( , G)
(3- . 2 (NAP-2). ,
, , , ,
, . ,
,
.
, ( I I )
FcyRII
() .
, , ,
, FcyRII
, ,
.
FcyRII , ,
.
, :
II, ?
,
FcyRII
.
.
.
,
FcyRII / 131 FcyRII:
, , in vitro [Gruel Y.
etal., 2004]. II .
: , [Jang I.K. et
al., 2005]. PF4
12- 14- ( 3600 )
( ).
,

.
,
: PF4,
.

. PF4

. ,
PF4 ,
.

PF4 .

424

, PF4
.
:
(
).

. , PF4
- .
PF4
-,
PF4. -
, PF4
, , ,
, , , ,
. PF4 ,
, ;
.
- PF4
, , . , PF4 (). ,
, PF4
,
PF4, .
(27 ME
1 PF4) .
4-,
.
,
PF4 , , ,
,
PF4 .
- ,
, , , PF4. ,
.
PF4 ,
PF4 , ,
, .

- .

. ,

II. IL-6

:

3. , -

425


4. ,
II

,
,
P F 4 .
,
( 4-) IL-8
2 ( N A P - 2 ) . ,
PF4, .
, J. Amiral . (1996), ,
PF4 ,
IL-8 NAP-2.
, IL-8 NAP-2
, , , PF4.
. , -
, IL-8 NAP-2,
, .

PF4, .
PF4 ,
,
. ,
, . , ,
:
(.. , ),
,
. ,

,
, , ,
. ,
, ,
II.
PF4,
, , ,
. , .
IgG-, ,
IgM IgA ( 20% ).

( FcyRIIa).

, IgM- IgA-.
11.
, -

426

. ,
;
. I g M - IgA- PF4
, IgG-; ,
IgM IgA,
.
,
-.

.

3.2.5.

()


, .
, -

.
,
,
II.
;
, . .
, , ( .);

,
,
I II:

,
II. , II -
, :
1) ,
;
2) - ().

.
:
50% .
,

.

PF4.

flflpafl- , -

427

:
A T III;
PC;
-.
II
, , ,
(timing), ,
(other explanations) [Warkentin .. et
al., 2005] (. 3.12).

,
- . ,

(. 3.13).
,
.

3.12
( )
,
2
1
0





5 0 % 3 0 -5 0 %

3 0 %

> 10 ; < 1
, 5 - 10-
< 4
*, < 1






(
(
II
,
,
31-100 )
30 )



II
,
, , ,




II:
6-8 (> 80%);
4-5 ;
0-3 (< 5 % )

428

-
3.13

1
2
3
4
5
6

()

(SRA)
- (HIPA)
-

V
-

PAT, SRA H I ;

, - .

(), ,
II ()
(0,5 /), (100 /)
. , -
.
,
, ;
, .

;
-

,
. ,
.
( 40%),

.
(SRA) *
.
(6080%).
, ,
,
.
,
, .
, ,
, (, ,
) .

,

fffau 3. , -

429

. -,
.
,
. -,
, , (0,10,5 /).
. , ,
.
, .
,

, .

FcyRII,
, .
,
. FcyRII
,
, HLA.

PF4 (ELISA)
J. Amiral 1992 . ,

: , IgG
IgG,, IgG2 IgG3. , ,
. ,
,
. , 11
, PF4 (IL-8, NAP-2).
IgG PF4 50% ,
,
20% .
1%
PF4 .
,
2% [Warkentin et al., 2000}.
ELISA
4-- [Warkentin .. et al., 2005].
, ,
.

PF4.

. , II
, ,
.

430

(,
)

- ( ,
)

___________ - - _______________
. 3.4.

,
.
, ,
. ,
Fc- .
,

.
.
(. 3.4).
3.2.6. II

II
( , ).
110 .

II,
.
(2550%); 5%
[Comunale .. et al., 2004].
:
(
, , );

;
, ;
;
;
;

^. , -

431

I ;
I
; g
| ,
.
,

.

. ,
.
()
(, , , ),
2002 .
(. 3.14). ,
.

-- .
,
1 100 .
, in vitro
[Amiral J. et al., 1997]. ,

[Kuo .. et al., 2005],
.
.
(
).

.
[Mazzolai et al., 2006;
Wijesirivardana et al., 2006].
II
. (-1 -2),
120 II,
() . ,
, ,
II 25,1% (
-1) 31,9% ( -2) 52,1%
( = 0,004) [Greinacher et al., 2000].
.
[Bick R.L.
etal., 2006]. ().
()
(,
, ).

......

0 ^ - /^ .
433

434

. ,
, --. ,
, . in vitro
: 18%
100% .
II.
, ,
, II , ,
, , .
, ,
, , ,
(. . 3.14).
, ,

,
( 6 .) . , ,
2002 . .
2250 ,
400 / 4 , 300 / 4
200 / .
15002500 /.

. in vitro

, . . .
,
, .
(
) . ,
.
II. ,
. ,
. 40 .
2 //
, 1,52,5. 75%
, .

.
15
6,9% ( 54%),
[Lewis et al., 2001].
:
; -

, -

435


,
.
.
.
.
2070 /.

,
12 . (, , )
, .
, ,
, .

. ,
II.
.
, ( ), II .
, II ,
,
[Selleng . et al., 2005].
, ,
,
.
.

(GPIb/IIla),
II. , GPIIb/HIa
. ,
,
. In vitro GPIIb/HIa
,
, . Fc-
GPIIb/IIIa,
GPIIb/IIIa .
,
,
.
GPIIb/IIIa
.

II.
().

- .

436

II, ,
PF4,
PF4 ,
, , . 6 10
;
10
.
, , 1800
.
, 1714
. .. Rosove . (2005)
in vitro,

39 II.
79,8% ,
3,3%.
, , ,
;
.
.
,
II.
II
II,
-, , ,
, .
II - .
: -, ;
-,
, .
, ,
.
, .
3 ,
.
( )
-
IgG, Fc-, .
, .

II . ,
II

, .
1 / .
2 .

3. , -

437

(
)
[Warkentin .. et al., 2 0 0 4 ] .
( 3 0 0 0 0 6 0 0 0 0 /),
( 5 0 0 0 0 2 0 0 0 0 0 /).
8 ;
2 0 0 /. ,
.
,
. ,
, (
) ( .) .
,
, . ,
,

.
, /
( .).
- II
,
, ,
, ,
.
, II .
.

3.2.7.

, :
1. /
.
.
. Tardy . (1999)
10,4% 1,7 ,
50%. ,


, .
,
, ,
, [Wallis D.E. et al., 1999].
2. (
)

. ,

438


.
3.
,
(1,52,5).
( 100 10?/, 150 109/ ) [Hasseletal .
2005]. (5 /).

5 ,
, ,
.
4.
. 510
( ) [Warkentin .. et al., 2004].

. ,
.
5. II , . II
, , , -
, , .
, ..
,
.
6.
, -

.
,
30-80 . ,
, ,
(414 ).
100
.
. II
,
II .
,
.


. ,
,
.
VII American College of Chest Physicians ()

(. 3.15) [Warkentin .. et al., 2004].

439

-|||> , -

3.15

,
, 4-
, 14-
,

,
(0,1-1%)
, 2-3 4-
14-

,
,


(< 0,1%)
, .
:
1

I
1 II III
[Bick R.L. et al., 2006]
(>

1%)

.
. ,

, , ,
, .
,
II
.
,
.

3.3.
() -
()
3.3.1. ,
,


Moschowitz 1923 . 16- ,
, , . -

440

. 1955 . Gasser .
5 ,
,
- .
- ()
().
Symmers . (1952).

( ),
,
.
.
,
.

, ,
. , : ,
, ,
.
,
. ,
, . ,
, , ,
. -, ,
, .
. T.J.
. (1995), 1968 1991 . , ,
3,7 1 . ,
, ,
, , - .
,

. ,
-.
,
( 40 ).
,
. , 40%
.
78% , '/ 3
[Furlan . et al., 2001].
.
,
, . .
.
59% ,
24% [Ruggenenti P. et al., 2001]. -

. , -

441

# (/),
. ,

, . ,
, .
. ,
, ,
/.
, - Shigella
. coli. ,
/ .

. ,
, vWF,
.
,
vWF.

,
, , .
1942 . Mark Altschule ,
,
.
D. Mitra . (1997), /

,
. ,
Fas- (CD95)
, , , .
/
.
,
/.
, T N F-a
Fas-.

/.

, , ,
. /
,
,
.
/

442


.

3060%
[Ruggenenti P. et al., 2001]. ,
.
,
. ,
, , .
,
. ,

,
(. 3.5).

. 3.5. /

443

3. , -


( . 3 .1 6 ) .
3.16
,

1. : ADAMTS 13 vWF
( AD AM TS 13)
( AD AM TS 13 IgG)
( )
2. :

(, ) : --

:
( )
(, ) ( )

3. /:
(, ,
)
(, S. pneumoniae)


(, )
,


/

4. -
5.

______________ _______________ _

3.3.2.
/
.
Adam 1 9 2 7 . ,

.
, ,
, .
. 90%
. coli 0111: 4. 1977 . Konowalchuck . ,
. coli Shigella disenteriae 1
Vero ( ),
-, . 1978 . Koster
. , , ,
S. disenteriaemna 1, ,
.

444

, .
J983 . - Riley . ,

- coli 0157: 7. 47 (
) . coli ,
. Karmali .
-, , ,
-, . ,
- .

, .
2,1 100 . .
5 , (0,5 100 . )
[Ruggenenti P. et al., 2001].

. , 35%
3-18%
. 10-42%
(, ,
), 1022%
, 29% [Ruggenenti .
etal., 2001].
--
( 80 ). ( ),
. 25%
-- . coli.

. 90%.
() .
, ,
Streptococcus pneumoniae, , , .

, , , .
Klein . 1997 .
2 , ,
.
IgM, IgM
. ,
, S. pneum oniae ,
, ,
S. pneumoniae, .
N - () . , S. pneumoniae

,
IgM. ,

3. , -

445

,
.
I g M
- ,
, .
/, . 1231% /

[T h o m p so n .. et al., 1992; Oklahoma TTP-HUS registry, 2001].
, 11 % / I
, 15% I I , 74% I I I
.

. /
7 . /
, HELLP-,

. , HELLP
. , Katz . (2000), 60%

. , /
,
HELLP-
/.
/ HELLP-
. , HELLP
( 72
), ..
[McMinn J.R. et al., 2001].
/
.
/ 95%, 80% [George J.N.
etal., 2004]. , /,
,
.
/ I
HELLP- , . .
.

. , .. Mokrzycki . (1995)
/
6 .,
. , ,
/, ,
, [Shamseddine A. et al., 2004].
, I ,

446

, , ,
/ .
,
, /. K.R.
. (1997), /,
, . W.R. Bell
T.S. Kickier (1997) .
23- 73 . ,
23- ,
,
.
.
/, .
( , , ,
) , ,
.
, .
In vitro
, .
/ (1
1600 ).
, ,
, C.L. Bennet . (2000),
/ 11 . 10
2 . .
,
. ,
.
,
, GPIIb/IIIa
vWF. , ,
, vWF-,
IgG . ,

.
/, ,
vWF- .
, , .

.
,
. -
.
^.

vWF , .
, -

. , - __________________ 447
r Y. Schmidt . 1991 ., 20
. , ,
. 4 5%
.

3.3.3. /

J.L. . 1982 .
vWF

vWF .
, vWF ADAMTS
13 (a disintegrin and metalloprotease with trombospondin type 1 motifs 1).
,

vWF- [Raife T.J. et al., 2001].
vWF-,
.
. Furlan . (1998)
vWF-
. ,
.
ADAMTS 13 , ,
, (
, , ). , . Loirat (2001)
5 , 2
15 214 ;
vWF-.
,
. , ,
, ,
vWF-.
.
vWF ,
225
Weibel-Palade
- .
vWF
189, 176 140
ADAMTS 13 , ,
[Furlan . et al., 2001].
vWF
.
vWF,
,
.

448

vWF , vWF
lb ,
vWF
. , vWF 10
vWF [Lamelle . et al., 2004].
, ,
vWF.
, vWF,
vWF
[Furlan . et al., 2001].
,
vWF . ,
vWF ,
. ,
vWF
. vWF-
( 50%) ,
.
, vWF- .
, vWF-
.
, , vWF

. ,
vWF;
. ,
, vWF
, . , ,

ADAMTS 13. , ADAM TS 13
,
50%.
,
vWF- .
,
80% 20
[Sohiphort et al., 2003].
vWF [Furlan . et al.,
1998].
ADAM TS 13,

. . Furlan . (2000), ,
,
,
, .
, vWF
. -

3- , -

449

, vWF-
24 [Furlan . et al., 2003].
vWF-
, vWF-,
. vWF,
, IgG;
(, ). vWF- 3 .
.
,
vWF
vWF, vWF. vWF
.
vWF:
, 842843
[Tsai .. et
al., 2004]. ,
,
vWF.
vWF
, ,
. G. Remuzzi . (1996),
,
,
vWF.
,

.
, vWF (140,176 189 ),
, ,
ADAMTS 13 [Furlan . et al., 2001]. ,
vWF
vWF-,
. , ,
(, ) vWF.
-,
.
- 2% .
,
[Furlan . et al., 2001]. - .
- vWF
205 85 ,
GPIIb/IIIa .
W.G. Murphy . (1987) 15 (
1S -

450

) ,
. -
,
2-
(). ,
-
- .
,
,
. - .
, vWF, ,
, -; ,
. , -
,
vWF.
/
,
. , Leung 1988 . / , .
, /, ,
.
, IgM IgG. in vitro

/ .
/ ,
[Hamasaki . et al., 2003].
-,
.
1980 . Monnens , .
, ,
/
( , / ),
.
,
,
,

- 5-9.
, CD36 ( IV),
[Furlan . et
al., 2001]. , CD36
,
.
/
. , .
, ,
vWF .

3. , -

451

3.3.4.
/

, /
,
/
.
/.
. Furlan, .. Tsai
.. Lian, ADAMTS 13.

ADAMTS 13, , ,
, ADAMTS 13.
vWF-
.
vWF- 180 ,
vWF 842843' . ADAMTS 13 .
ADAMTS 13 9q34. vWF-
29 ADAMTS 13 [Lammle R.
et al., 2005]. ADAMTS 13
, , , . -
().
ADAMTS 13
.
ADAMTS 13 (S), (), , (dis), 8
1, (cys), 2 cub
[Lammle R. et al., 2005] (. 3.6).

. 3.6. ADAMTS 13


ADAMTS 13. 75 ADAMTS 13,
vWF-
. , ADAMTS 13
,
50%. ,
ADAMTS 13 ,
,
. ADAMTS 13
.

,

452

,
.
. Furlan . (2001) 1996 2000 . 239
/. 23 239
vWF-.
( 5 ),

(2030 ).
. ,
vWF-
,
vWF- . . Furlan (2003)
, vWF

5% vWF-. , ,
Pro475Ser vWF-,
5% 5% . , . . vWF .
, vWF ,

, . ,
, ,
. , 2
vWF-
;
. ,
27 44
vWF-,
[George J.N. et al., 2002].
,
ADAMTS 13 .
/ (2001), 16 48
ADAMTS 13,
32 .

- , ,

ADAMTS 13.
. Raife . (2001), 40%
vWF-.
ADAMTS 13
vWF-.
. , D. Studt
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2005. 0 7 .- 1.
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.. . ., . .
/ / . . 1996. . 42.
4. 25-27.
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/
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4. (). .

617

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. 2000. N 3 . 2127.
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. - 2002. - 5 . - . 15-19.
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, 2001. ' 160 .
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1999. - 5, - . 19-20.
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. 3741.
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. - 1998. - 6 . - . 71-82.
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. . . /, 2003.
/ . .. . ., 2002.
. 423-441.
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. : . . ., 2001. 90 .
. .
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618

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/ / . . 1999 4.- . 7-13.
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) / / . . 1998. 4.
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) / / . . 1999. 6 . . 1318.
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-35 / / .
. - 2002. - 6 . - . 37-39.
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151,193-196.
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: . .... . . . ., 2002.
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/ / . . 2003. - 4. - . 2630.
.., .., . .

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.. / / , 2001
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.., .., ..

/ / . . . 2001. . 7. 3. . 6-10.
.., .., ..
( ) // . .
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.., ..
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5.1.
-
, : ,
, .


. ,
.
- ,
.

. , ,
750 . .
(Centers for desease control C D C ),
13- , 10
139% .
,

, .

, ,
36 60% [Jacobi J., 2002].

,
, .

5.

631

5 1 .
. 5-25% [Lapinsky S.E. et

al., 1997]* 35%


- .
,

, .
, ,
, .
,
, , ,
. , ,
, ,
, ,
,
, , ..
.
,

,

.

5.2.
(. sepsis ) IV . ..

.
(460370 ..)
| , ,
. . (15171590)
(1493-1541)
(),
.
XIX . ,
,
. - .
1865 . . .
, .
,

.

XIX .,
.

632

1914 . X.
,

....
.

,
.

.


. 1894 . (G . Sanarelli)

24 . ,

, . (G . S chw artzm an) 1928 .

. typhosis 24
, ,
, .



24 .

.
,

. 1955 . . Williams
Studdiford (18971964)
-,

. Williams studdiford
Bellevue - , Gordon
Watkins Douglas (. 1921 .)
,
. 7 ,

,
.
.


. Studdiford D ouglas ,

Gordon Watkins Douglas

5.

633



,
,
( , , ,
, ),
(, - , ),
( -
, , , ),
.



.
Roger . Bone
1992 .
(1941-1997)

(American college of Chest Physicans )
, (Society of Critical
Medecine SCCM ), ,
.

(Systemic Inflammatory Response Syndrome SIRS).
Roger . Bone.
R.C. Bone .
,
. 1977 .
. 1985 .
, 1992 .
Rush Medical College. ,
, -.
R.C. Bone 900 .
SIRS (
) CARS ( ).
, , , Roger . Bone
56 .

40 , , .


.

.

, ,
,
,
.

634

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, SIRS,

: , , , ,
, , ,
[Jacobi J., 2002].
, 1992 .,
: , , , , ,
()

,
(. 5.1). , ,
, ,
.
5.1


:
> 38* < 36 > 90 ./
> 20/ 02 < 32 / ( ,
)
> 12 109/ < 4 109/ > 10%

,
,

,
, ( , , )
,

,
,

, .
/-
< 90 .. 40 ..
. ,
,
,
,


,

635

. , 7%, 16%, 20%, 45% [Blackwell T.S. et al.,


1996].

5.4.


,
,
,
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, -
.
,
, (, ),
,
,
. ,
, ,
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.

,

, ,

.
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, (. 5.2).
,
,

(-).

,

. R.C. Bone 1997 .
(Compensatory
Anti-Inflammatory Response Syndrome CARS).
CARS .
CARS ,

636

5.2
,

:



-

,
,
,
.
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, , , ,
(. 5.3).

.
:
1) ()
;
2) ()
;
5.3



a (TN F-a)
(-1 , -2, -6, -8,
-15)
- (-)


-1 ( -IRa)
-4, -10, -13
-1 II ( -IR II)

, (TXAj)

(PAF)
(TG F-p )
\ (,)
TN F -a
1 4
( )

(LPB)
(PGI2)

()

5.

637

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TNF
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:
IL-1R, TNFR - IL-1 TNF-
PAF -
P G -
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IL-8

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638

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.

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(),

(
).

-

. 5.2.

5.

639

. CARS
,
,
.
CARS HLA-DR (
11 ) 30% ,
(TN F-a,
-1) [Bone R.S. e t al., 1997]. CARS
, ,
.
.


(. 5.2).

5.4.1.

.

,
, , ,
, , ,
.
,
, , - , , .
100
.
( T N F - a , -1, -6, -10),
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-, - , V E G F , P D G F ) (. 5.4).
5.4

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,

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-

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640

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II .

(ELAM-1, IC A M -1 ).,
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,
,

-
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-10
-13
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-,

- -,

-,

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TN F -a -1

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VEGF

,
, ,

,
, ,
, ,

,
ANCA-


,

.
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,

. ,
,

.
.

5.

641

:
,
. ,
-, ,
.

,
.
,

.


.
T N F -a , -1(3, -6 -10.
.

(TN F-a, - ).
,
[Blackwell T.S. et al., 1996].
TNF-a ,
, ;
90 .
-, -6, -10, TN F-a.
-.
- 1 (Thl),
-2, -, T N F -a - 2 (Th2),
-4, -5, -6, -9, -1,
-13. T hl , Th2 .
. -, 8+-, NK-
, -12, ,
ThO T hl Th2. -4 -10, ,
, .
/2-
. ,
T h l-
.
: , , .
-.
,
:
I ( )
( -2 - 9, -1 1 ,12,13, -15, -, LIF, , );
II ( )
( - a , -, -, -10);
21 -

642

TNF (TNF-a, TNF-p, CD40, FAS);


(-8, RANTES, -l, PF4, NAP-2)*
Ig- ( -1).
,
, I
: -, -2 -6. -
-3, -5 -; -2
-2, -4, -7, -9 -15, -6
-6, -11, LIF (leukemia inhibitory factor, ,
), OSM ( ).
-
., - ,
-, ,
.
- .
-.
,
.
-6.
gpl30,
.

. , -3, -5 -

.
. , -3 -
; - -3.
-
, .
(TNF-a, -1, -6)
,
(, , -, , ) -
,
( (TF)
S. T N F -a

(ANCA) . ANCA

, , ,
. T N F -a -
Fcy- ,

.
(VEGF),
TNF-a -6. VEGF

5.

643

.
-,

. TGF-,

(TNF-a, -1, -8). ,

, .

. ,
TN F-a .
, TNFB2, TNF-a
,
. -10
.
-lRa ,
.
.
.
TNF-a ()
17 , ,
- () [ .., 2000].

, ,
(, ), . TNF-a
:
, ,
, (. 5.3).
,
. -2, TNF-a
-. T N F-a
.

TNF-a ,
. , TNF-

() . , TNF-a

[Elkind M.S. et ., 2002].
TNF-a,
: 55 75
55 75 . ,
55, TN F-a . 55 TNF-a
,
TNF- (TRADDs), , ,
.

644__________________ -

. 5.3. TNF-a

, -1, -
-18 ,
.
,
T N F -a (
, ,
). T N F -a
. , T N F -a
,
, [M artin . et al., 1994].
T N F -a
[Pinsky M.R. et al., 1993].
-1

-l a -. -1
,
.
-1, TNF-a.
- ,
, , ,
, , .
-6, -8, -2, T N F -a , -1(3
.
-1
-IR . : -1-

5.

645

( -1R1 -1RII)
(-lR-AcP). ,
.
IgG- .
, -IR I 45% 11- (TLR), . , -1

[Greenfeder S.A. et al., 1995]. -lp
.
- IgG-
-IR I. -IR I
- IgG-
-IR I.
- -IR I -lR-AcP,
. -IR II
-1(3.
-1RI , -1RII - 1.
-1(3 II IRa
-IR I. , II IRa
-1, -6, -8
[Fisher . et al., 1992]. -1(3,
T N F -a , . L.S.
Casey . (1993) , -
, ,
.

.
.
-6 26 ,
, ,
,
. -6 - -, ,
, . , -6
-
(). -6
.

. (T N F -a -lp )
-6, . H.R.
Michie . (1988)
.
T N F -a 6090 , -1 4
. coli , -6
6 . ,
, T N F -a -1Ra
-6 [Fisher . et al., 1992]. , -6

646

, ,
. - ,
() ,
, -6.
-6
. , -6
[Van der Poll .
et al., 1994]. , -6
. S. Oda , (2005) ,
-6
.

,
, ,
() (sR).

.
TN F-a (55 75), -lp, -2, -4,
-6, -, -.
. , RJI-2R
-
,
, , .
,
,
. -1 -lRa.
-1, -1Ra ,
,
. -lRa: ,
, , ,
, . 1Ra , (), TNF-a, -.

. ,
.
, ,
.
TNF-a (sTNF-aR) -lR a T N F-a -10
10100 [Blackwell T.S. et al., 1996]. , ,
, sTNF-aR
-lRa [Ertel W. et al.,
1994]. ,
.
, ,
.

5.

647

-10.

. In vitro -10
TNF-a, -lp , -8. -10
TNF-a ,
-10 TNF-a
, [Gerard G. et al., 1993]. ,
-10 .
, , -10,
[Mallat Z. et al., 1999].

. TNF-a
, ,
. TNF-a
,
t-PA u-.
1-1 TNF-a.
TNF-a - ; , F1+2 -
. -1 ,
; -6
. -10
.
-10
.

(NF-kB, -1, NIAT, STAT). NF-kB,
, ,
. NF-kB
,
(. 5.5).


,
. NF-kB
: 5.5
, N F-kB

TNF-a
-1
-6
-11
-

-8

RANTES

NO- (iNOS)
-2
Ag
5-

ICAM-1
VCAM-1
-

648

, ,

.
iNOS N0
, , ,
, .
.
NF-kB, ,
.
NF-kB ( -10, TGF-p).
, NF-kB,
, (TN F-a, -lp),
, ,
. NF-kB
IkB.
IkB. NF-kB
.
, ,
, . :

.

. 30
,
,
,
, , -
.
CD1 lb/CD 18, p-2-,
,
().
.
CD 14.
, CD 14 ,
.
toll-like receptors, toll-
(TLR), ,
CD14 [Poltorak A. et al., 1998].
,
,
() CD 14 (sCD14),
.
CD 14 , (, , -
), -, .
.
CD 14 .
TNF-a -

5.

649

.
CD 14.
sCD14. sCD14

, -6, -8 . sCD14
TNF-a. ,
sCD14
[Bucala R., 2004; Landmann
etal., 1995].
CD 14 sCD14
. CD 14
,
TLR.
11- Drosophila melanogaster. 10TLR.
TIR- ,
Toll/IL-- (T1R-). TLR, TIR-
,
(-IRI RJI-18R), ,
MyD88, TLR.
TLR
. , TLR2 TLR4
,
. , TLR4
,
TLR2, ,
, a TLR3
NK-.
58
60,5 ,
, , .
(115 /), ,
23- [Edwin et al., 2003].
-1 -6.
.
CD 14, ,
. ,
.
, , CD 14
. ,
CD 14,

. , , , .

TLR CD 18 2-. , - L-.
.

650

-,
,
. -
, -
. - , : SR-AI, SR-AII, SR-III,
MARCO. , -
(). ,
.
,
CD 14.

,
, 80 130
. , ,
.
,

. -8, , ,
, , , , ,
NK-; .

. ,
, ,
. ,
.
50 15
.
:
1) --, ( -8);
2) ---,

- l
(macrophage
inflammatory
protein ), -1 (monocite
chemoattractant protein ),
RANTES (regulated upon activation, normal T-cell expressed and secreted
-,
-),

.
, 7
, : .

G -
- .
. ,
, ,

5.

651

.
,

.

-8 . 56
-8 - lp T N F -a.
, , , -8,
20 [ .., 2002].
, -10, - 1 T N F -a ,
-8.
-8
[Marty . et al., 1994]. , -8
- (). ,
-8 ,
,
[Chollet-Martin et al., 1993].

,
, .
;
: , ,
.
(P G ), PG , (LT), Aj (^.
,
.
PG ( PG E,,
PGI2), , PG,
,
. ^
P G D 2. PG
, , LTB4. PG
.
, , , ,
,
. ,
PG
, .
PG : G -
(E R -4 P G E 2) (PPAR),
.
,
^

()
.

652

: -1 -2. -1 KQ
, (
). PG,
,
. -2 ^.
( )
-2 ( 50 )
NF-kB.
, -1 -2
. -1
, -2
, . , ^,
-2
. ,
, . -2
,
-2.



. , ,
.
. ,
,
.
;
, ,
. ,
,
5 5 5. 5
,
. ,
.


.
.
,
, .
. ,
.
.
. ,
,
.
. , , 4, 5

5.

653

,
, ,
.
5
. ,
,
, .

,
, , .
,
, ,
(. 5.6).
-1, -6 T N F-a.
, -, -
-, , , .
-6, -1 T N F -a
N F -- (,
, , ). /,
. , NF- /

,
. N F-
/,
.
, ,
,
- .
,
, .
,

2327 . ,
100 .
46
2472 .
;
(ICAM-1, VCAM-1, -),
PAI-1
, ,
Clq, .
*
. ,

654

5.6

,

,-

, -

VIII

C1s
2

, 4, 5
,

2
-1
,
-

H.D. Danbeig . (2003),



.
-
.
. ,
D. . (2000) ,
, ,
80%,
20%.

5.

655

5.4.2.
,


.
, ,
-,

. ,
, , , , ,
.


, .

,
.
,
, ,
, ,
,
. ,
, ,
(. 5.7).

.

.
,
, (T N F -a , - , -6),
, ( ,
), .
1960 .
Williams-Kretschmer .
. Pober 1988 .

,
.

. ,
, ,

;

N 0 . ,
, ,
, ,
, , ,
.

656

5.7


:


-1
Ag
2
II

N0

N0

-
/-
(PARs)


IXa, Villa, ,
vWF, ,
-, / III

S
/
(EPCR)
(TFPI)


(t-PA, -)
t-PA, u-PA (t-PAR, u-PAR)

(PAI-1, PAI-2,
PAI-3)
,
(TAFI)

-1
(PDGF)

II

N0

TGF-p

(VEGF)

5.

657

(-, ICAM-1, VCAM-1)


(-8, -1)
(PAF)
PARs
II
1

(TGF-a, -10, -IRa, -13)


N0


, , , ,
-, -

,
,
,
, ,
.
Cotan (1991)
: ,
(
, -, (vWF), PAF
), ,
46
( , ICAM-1, VCAM-1; -1, -6; -8,
-1; TF).

. ,

. :
1) ,
;
2) (N0 ),
;
3) , ,
, , ,
.

658


.
, ,
, vWF,
.

- ,


.
,
Fc-
.
.
( , ,
, , ),
.

:
(tethering),
;
(rolling)
;
;
;
.

-
( ),
, .


.
,
. ,
.

.

, N F-kB - .
30 ,
: , ,
(. 5.8).

(Syal-Lewis)
.

5.

659

5.8

CD34
PSLC-1
MAdCAM-1

L-
-
-

1C -1,-2,-3
VCAM-1
LFA-2 (CD2)
LFA-3 (CD58)
MAdCAM-1

a 4 p i (VLA-4, LPAM-2)
a4p7 (LPAM-1)
6 1 (VLA-6)
al_p2 (LFA-1)
2 (-1)
aX(32 (CR4, -1)

, ,
.
, ,
, (3.
,
.
MAdCAM- ,
, Ig- . MAdCAM-
,
.
,
, N -
2+- ,
,
. : L-, - -.
L-
,
.
- - W eibel-Palade

. (, )
-
. -

510
1060 .
-
( - , T N F -a ).
- 4 ,
1224 .
-
, , ,
.
,
, ,

660

- 0

. 15 - (
120180 ) - (90110 ),
20 . p -
(p i, 2, ), P-,
a - . 1- (CD 29 VLA )
- Hb/IIIa
( , , ). 2- p- (C D 1 1, , )
p- (CD 18);
Ig- .
.
, ,
- , . .
-1 ( 2- )
(IC A M -1) .

.

.
(ICAM-1 IC A M -2), -
( -1), (VCAM -1),
( ) 1 II .
IC A M -1 V C A M -1 T N F -a -1.
ICAM-1
. ICAM -2
.
.
IC A M -1 V C A M -1, - 1 T N F - a
- -.
. ,
C lq
-, ICAM-1 VCAM-1.

.
,
, (rolling) .
-
,
. ,
( -8, M IP -lb) ,
. G -
,
Ig -
. Ig-
.

5.

661

,
(, 5), (), ,
, PA F, .
-
, . ,
- PAF,
- PAF .

.
L- ,

.
.
,
, 1CAM
.
2- ICAM
, .
,
p i 2- .
, .

pi-, (32- 5-. ,
.
, ,
. 6 [Goldby R.A.
et al., 2002].
10 .
: , , , .

.

,
.
pi- 2-
C D 4 + - ,
.
,
.

: , , , ,
. ,
--

- /j

662

, ;
IC A M -1 V C A M -1,
.

() (sEsP-, sICAM-1, sVCAM-1).
. ,
TN F-a, -6, ,
.


(TF),

(. 5.4).
TF, V ila,
, . T F V ila

RMK

<---- Va-

:
.. ..
_ 2+ ^ ,
, Va, ,

II ( )

11 ( )


TF


. 5.4.

5.

663

X . X
TFVila ,
IX
1, V illa 2+ X .
, IX, TF
. ,
, Va, ,
2+
, (
). , , ,
VIII V. V illa 1

, Va ,
.
, TF,
, ,
, , , , .
, T F
. ,
.
TF VII, .
VII .
( 1%)
. , TF, VII,
.
.

(,
),
. IX, , X, , V, VIII
.
, ,
.
, .
, IX IV ,
.
.
avp3.
, ,

.


.

(t-PA, u-PA), (t-PAR, u-PAR).

.

664

t-PA .

. t-PA
.
.
,
t-PA, -II.
u-, ,
.
. , -
[Carmeliet P. et ah; 1994]. u-PAR
, , .
-, ,
PAI-1 PAI-2,
, .
u-PAR . ,
u-PAR
[Bugge .. et al., 1996].
,
, .
,
- 2-.
.
,
, (PAIs).
PAIs. PAI-1 t-PA,
u-. PAI-1 ,
, . , ,
, , PAI-1
. PAI-2 , ,
, .
1-2
. PAI-2
.
PAI-,
. PAI-
t-PA u-,
.



: III (AT III), (TFPI), PC. AT III
(),
, 1, .
( 58 )

5.

665


, . AT III ,
, , , - ,
AT III.
AT III, AT III
.
AT III XI .
,
AT III
. , , , HS ,
.

, - .
,
, II (-). -
. AT III,
, 100 .
- ,
.
- AT III
.
, -
. , -II

, , .
TFPI (Tissue Factor Pathway Inhibitor)
( ).
Kunnitz- . TFPI
,
. ,
TFPI.
V illa -TF,
.
,
PC.
(), PC PS,
PC EPCR.
PC , 50%
45
PC.
PC
. PC
, .
PC FV Leiden,
. PC

666

, .
PC
,

LD10 . coli.
.
,
; ,
.
: 1)
;
2) ; 3)
AT III; 4)
PC .
.

,
.

.

. PC
EPCR.
,
; Va V illa
,
. , V
- VIII, Va
. -
V Va.
,
.
PAI-, .
:
.
PC
,
EPCR . , EPCR

,
.
EPCR PC .
PC
.
Va V illa
PS. -
, . PS

5.

667

: 1) EPCR /; 2)
Va Villa ; 3)
Va
Villa. 60% PS 4- (4)
. 4
S, .
PS .
-
PC. PS
.



,
.
,
, N 0 . 1980 . Furchgott Zawadzki
, () . ,
,
(EDRF). 1998 . Furchgott Igrano
EDRF ,
N 0.
N 0 .
10-60 . N 0
.
N O -: 1) eNOS (NOS III);
2) iNOS (NOS II); 3) nNOS (NOS I).
N O - (, , )
L- L- N 0.
NO- ( 7, 17- 12-
). eNOS nNOS,
iNOS . iNOS
, . .
. N 0
, , ,
, , .
eNOS, iNOS.
NO-
,
N0 eNOS. , Fagan . (1999),
eNOS (eNOS/ ) ,

. ,
, N 0
, .

668

, eNOS, , , ;
(, , ), (
, , ). G q- -3- .
2*-,
eNOS. eNOS, iNOS -
. eNOS
,
.
1, L- N 0 .
eNOS ,
.
eNOS N 0 .
N 0
. N O
(-, - ).

2+.
-
N 0 ,
. eN O S
, (Akt),
. eN O S

. , eNOS. 3
eN O S
[Uematsu . e t al., 1995].
eN O S. ,
( )
eNOS,
. ,
.
,
N 0.
N 0
. N O N - -L-
(L-NMMA) L-,
,
, .
N 0 .
, L-NMMA
,
.
N 0 ,
. N 0 . N 0 ,

f- 5.

669

, , .
() N 0 .
N 0 ,
, ,
. -
, 2+.

,
2+ .
2+- 2+- +-
, 2+- .
2+- ,
2+ . - , ,
2+~.
. , N 0 2+- L-
. , N 0 2+-+-
, .
L-,
.
2+
()
() .
() . ,

. , N 0
.
, N 0
.
N 0 -
. , N 0
- , ,
. N 0 ,
. N 0
. ,

.
N 0
. , N 0 , ,

[Cooke J.P. etal., 1991].
24 . .
, , N 0

670

,
[Minor et al., 1990]. N0
. N0
[Hirooka Y. et al., 1992]. NO
,
eNOS ().
- ()
N 0 . ,
N 0 NOS.
,
NOS L-NMMA,
, , , , , , .
N 0
.
iNOS,
NF-kB.
N 0
. T N F -a ,
,
,
.
iNOS (iNOS/ ).
,

[Gunnett .A. et al., 1998]. N 0
( 0 0 N 0 - ) .
.
, .

/
,
. eNOS .
iNOS, eNOS
.
24 , 4872
eNOS,
.
, N 0
eNOS. , G/ 7- eNOS
298
, eNOS . Miyamoto . (1998),

5.

671

. 786 / 5- eNOS

eNOS. N 0 (VNTR)
4- eNOS. eNOS
- ,
.

(PGI2). PGI2 (IP-
) .
IP- , PGI2

. ,
.
PGI2 ,
, : , , AT II,
-1, 2- ,

. PGI2 . PGI2
, , N 0 ,
. PGI2 Gs-
, , .
, ,

.

,
. , ,
PGH2.
,
PG E2, PG I2, PGF^. PGH2 .
,
-
, .
, , , PGH2
, PGH2.
PGH2
. , 2-
.
,
PAF.
PAF , , .
, PAF .
,
, ,
. , PAF
.

672


. ,
E T -1, -2 -3 ,
. -1 .
: , . E T - 1, Yanagisiwa
1988 ., . -1
, 21 ,
-1
- . -1
, , , , A T II, ,
N O . -1
, G - .

,
. , -1

. . N 0
, -1 .
, ,
, N O -1
, . E T - 1
, . ,
, , -6 .
, -1
. -1
, , [Schiffrin E.L.,
1998].

.
, ;
,
.


150 ..,
4 0 ..
70 ..

N F-kB, -1, H IF-1 (hypoxia-inducible tra n s c rip tio n f a c t o r - 1,
1, ),
(P D G F -P , -1, V E G F , T S P -1 ),
, .
e N O S .
P D G F -P -1
48 .

fnaea 5.

673

. V EG F .
6 TSP-1,
, ,
, .
,
,

.
5.4.3.


.
,

.
. ,

.
,
, , .

,
- . ,
.

[G ando S. et al., 1995].
,
. ,
, ,
, ,
(. 5.5).

,
.
,
.
, .
XII . ,
XII
, ,
. ,
,
. T F V II/V IIa
T F P I
, XII
.
22 -

674______________ -

. 5.5.

TF .
46 ,
: ,
. TF , , , , ,
. TF ,
, . TF
. T F

, , .
TF 2 [Lopes-Bezerra L.M. et al., 2003].
TF
. ,
TF -6, PAF -1,
.
TF ,
, .
125- TF
.
TF, -6.
, -6
TF,

. ,
,

^ 5.

675

TF .

.
, T F ,

-.
-,
,
.
,
.
,
.
,
, TFVila, PARs (protein-activated
receptors, , ). PAR
, G -.
N - ,
PARs. 4 PARs. PAR-1
, PAR-2 , a PAR-3
. PARs-, -3 -4
. PAR-2, PAR-1 TFVila
[Levi . et al., 2004]. ,
, ,
PARs .
PAR-2 TFVila
,

(T N F -a, -1(3, -6, -8). ,
PAR-2
.

. ,
VII
-6 -8 . , PARs
. , PAR-4
,
. , TF
, .

TF [Levi . et ., 2004].

PARs, EPR-1.
, , .
EPR-1, -6, -8, -1
. ,
AT III TFPI EPR-1.

676

-

'
:

PFGF
(
) T G F -

:

-
Weibel Paladi PAF

PGDF

, PGI2

* -
. 5.6.

,
, .
, , ,
, (. 5.6).
,
XIII.
VIII V
. ,
.

,
.
PGI2 NO,
. ,
.
,
t-PA PAI-1. ,
PC. ,
,
.
(-, PAF) ,
, -1 .
,
, .

5.

677


, PAI-1
.
, .
.
,
PAI-1
( TN F-a -1(3).
PAI-1
-. , 1-1
,
-1,
[Hermans P.W. et al., 1999]. 2
.
F 1+ 2,
, ().
3
, .
, ,
.
T N F -a -lp
(-8, -1)
. ,
TLR-4,
.

ICAM-1. ,
ICAM-1 ,
, .
, u-
u-PAR, ,
. u-PAR
, . ,

u-PAR . u-PAR .


(, , ),
- . ,
u-PAR ,
.
,
-1. , , -

678

,
. 1-1
u-PAR ,
. In vitro
PAI-1 - TNF-a
[Robson S.C. et 1., 1990]. In vitro
.



.
.

: AT III, T FPI PC,
, PC PS, EPCR. ,
.
AT III
. , , AT III
-10.
, ,
. -, PC, . -,
TAFI (- ). TA FI,
,
,
. TAFI 5
, , -
. -, , , ,
, PARs.

.

:
T N F -a -6
.
TFPI .
TFVila, TFPI
. T F P I
.
TFPI
.

PC ,
. , PC

, PC
. -

5.

679


[Okajima . et al., 2001].

PARs. ,
PARs. ,
,
-
.
TN F-a, -1(3, -6,
-8 --
. PC
EPCR. CD1 (-1).
PC, EPCR NF-kB , ,
. EPCR

. EPCRPC
,
. .



. AT III, PC PS
-.
AT III, PC.
PC AT III

,
, ,
.
PC
EPCR .
PC
.

(T N F -a, -1(3). ,

.

.

, .


:
, , ,
.
.

,

680

- /

, , vWF, , , TSP-1,
. vWF lb
, ; , vWF

.

, PAF.

.

, .

(, , , TXAJ.

,

.
. -
(3-) 9 ,
, .

.
.

,

.

.
-, -.
-
, -.
- in vivo ,
,
. -

, .

. -
, . -
PSGL-1,
. -,
, ,
.

. , -
.

5.

681

-,
,
NF-kB ,
(T N F-a) (-8, -1).

, , , ,
.
,
-,
. (PDGF Platelate-Derivated Growth Factor)

. III (Connective Tissue-Activating Peptid III, .. ,
) . TGF-P
, .

, .
L- PSGL-1,

, .
.

5.5.
) ,

,
.
, ,
,

.
, , (, ).
, 8
10%. I II
( , ,
).
1314 . . ,
, ,
.
( 15 )
,
.

(, ,

682

, , ).
,
, .
.

.




, .
,
, -
.
-,

.
- ,
(, ,
, ,
),
, ,
, ,
( )
.

, ,
,
,
, ,
.
,
.
90% .

[Brealey D. et al., 2002].

, 68
. , -
, , . , ,
. ,
.


, ,
, , ,
.

5.

683

,
.
,
, ,
, ,
.
:
, ,
.
, , .
( = 9585 ..), ,
;
, ,
, .
, , , , . (
< 70 ..), , ;
( )
.

, .

,
, .



,
. ,
, ,
.
( ),
.
, ,
.
, -
.
.
- ,
.
.

- , , , , , ,
.
,

684

, , , , .
, ,
,
.

20 40 .
.
,
.
,

.
,

. ,
(, , , )
,
, ,
.


.

:
1) ,
30 ;
2) 4 ,
,
;
3) ;
4) ,
;
5) , ;
6) ( , , ,
);
7) , , , , pH ;
8) (
), ,
;
9) ,
, , , - , AT III, .
-

().
, - .
97,6 98% .

5.

685


56% 18 - [Toh . . e t al., 2002].

.

() 2+.
2+
C ab an a (1982).

,
. ,
,
.
. .. Toh . (2003) ,

.
. ,
.
,

, .
, . (
, , , ,
, , ,
, , ) ,


.

. ,
.
(),
( );
.

, .

.

.


,
, , -

686

, ,
, .
:
() 90 ..;.
30 /;
02 60 ..;
;
;
;
.
:
1. , .

,
.
:
,
46 , ,
, ,
, ,
,
.
-
.

,
( AT III PC), .
2. ,

.
IIIIV , , .
(
) ().
.
3.
,
, , (, ), (),
, , .
,

.
, (
0,51,0 /).

5.

687

4.
.
5. , ,
.
.
6. - - .
7. ( , ,
).
8. - ,
.
().
,
TFPI.
-,
.


.
9.
.
10. ,
(20004000 ).
11. , - .

.
.

. :
, - ,
. -
-
. , 25% ,
, .



- ,
, .
,

40% [Horn et al., 1998].


.

688


,
.

, .

. ,
,
, (T N F -a, -,
-6), , , PAF, N 0 , .
T N F -a . ,

.



,
. (-1 )
(5)
in vivo, in vitro,
[Warren H.S. et al., 1993].
( IgM
) ,
[Haria et al., 1996]. - R.L. Greenm an
. (1991) , 5
, ,
Bone . (1995) .


in vivo, in vitro. ,
.
,
,
[Horn et al., 1998].

C D 14 .
, () CD 14 (sCD14)
,
[Burgmann . et al., 1996].
sCD14
.
.
BPI (bacterial/permiability increasing protein, .. ,
) -
. BPI ,

. in vivo, in
vitro , BPI --

5.

689

TN F-a [Fisher C.J. et ., 1994].


1, .
N - 1
23 . In vitro
(RAW 264.7),
- BPI, TN F-a
[Dahlberg P.S. et al., 1996].

BPI .
( , , )
T N F-6, .

. B.R. Gordon . (1996) ,

.
, . ,
[Astiz .. et al., 1995]
,
.

.
. -,
, . ,
, ,
. -,
.

,
.
,

.
, , ,
.



(T N F -a -1)3),
. ,
TNF-a - 1
.
(sT N F -a -IRa)
[Abraham ., 1999].

.

,
- , . ,

690

IF N -y
. -8
.
, ,
, .

. , T N F -a
-lp , -6, -8
. //- .

, C.J. Fisher
. (1993) T N F -a
( ) T N F -a.
INTERSEPT (1996) NORASEPTII
(1998)
T N F -a .

.
, -,
,
, ,
, .
T.J. Evans . (1994) T N F -a 55,
75 .

.
-IRa, ,
, ,
, -Ra
. , -Ra
,

.

.
,
, , T N F -a .
, T N F -a ,
-6.

. ,
T N F -a, ,
,
. In vitro , CD 11,
C D llb , C D llc , CD18,
.

5.

691

,
, - ,
TNF-a.

N 0
NOS
. NOS L-NMMA
[Kilboum R.G. et ., 1990].
-
A. Petros . (1994). iNOS
. NO-
. , A. Petros
. (1994) NO-
.
, iNOS
. . Nava .
(1991), L-NMMA
, L-NMMA
. ,
eNOS N 0
. , NOS
. .



(AT III, PC PS, TFPI)
.
PC

.
Gordon . (2001) , (
) - -6
.
,
PC.
PC (PROWESS) ,
PC (,
) 28-
.
, .
,
.
.
19,4%.
(Food Drug Administration FDA)
,
, , PROWESS,
,
( APACHE). ,

692

- 1

PROWESS
,
22%
. ,

28- .
-
ADDRESS ( ()
)

, [Laterre P.F. et al., 2003].
. Roque . (2000) TFPI

.
TFPI . , .. Creasey .
(1993) . Abraham . (2001) TFPI
,
. Abraham . (2003) , TFPI
. ,
TFPI
.
de Jonge . (2000) ,
TFPI
.

, 1
(1-), XII .
PAF.
PAF
, T N F -a
.
PAF .
.
[Fein .. et al., 1997]

.
.

, ,
.

N 0 . N 0
, ,
.
NO- (L-NMMA)
[Li S. et al., 1996].

5.

693


, . ,
(, )
, . . PG E,
- T N F -a.


, ,
, ,

.

. , CD 18


[M cD o n ag h P .F. et al., 1996]. - -

[Hansbrough J.F . e t al., 1996].
, ,

.

. N A D PH -,

, .
N A D P H -
(DPI) ,
, ,
. DPI
N 0
, .


.
,
,
( ).
. ,

.
.

N - ,

.

. -

694

( ) . ,
(-4, -10, TGF-R
-), (-IR, sRTNF-a),
() [Liu . et al., 1999].

, ,
.

,
.

.


.
,

(, ).
,
, , ,
. -

.

.

5.6.


,
,
, .
,
,
.

, .
,
.

- - -, ,
(NK-).
,
.

5.

695


.

,
N-.
,
, .


. 1
(--1)
.
: CD lib, CD 14,
CD64, , .
,
, ,
NO-.
N K -
, , NK-
.


, 4 50.
,
,
[Sacks G.P. et al., 1999].
,
- ,
5+-, .
IgM IgA , IgG
, , , . ,
,
, [Shoenfeld Y. et al., 2004].
,
CD4+ -
CD8+ -.
CD4+/CD8+,
.
.

, .
,
(, , )
- ,
, .
.

696

, ,
. ,
,
.
,
, .

,
.
.,
, .
- -
-. - 1-
(Thl), , -
2 (Th2),
.
Th2, .. .

,
.
Th2 ,
.
2- T h l-
[Hill J.A. et
al., 1995]. T h l
, ,
NK- . ,

2- T h l-
(. 5.9).
5.9

Th1-:
-2
-
TNF-a
2-:
-4
TGF-0
-10

-, ,
, ,

-, , Th 1-,
, -
, ,

: () ; () ; (?)

.

5.

697

, - .

, , -1.
,
, ..
, Th2,
.

,

. ,
, ,
(CCL5/RANTES,
CXCL1). ,
(-, )
,
,
. , ,

.
, ,
, ,
.
- T G F -p [Spencer .. et al., 2004; Robertson S.A. et al., 1997].

HLA-G, . ,
HLA-G [Hunt J.S. et al., 2005].
,
:
.
HLA,
.
,
(7)
.
, (
TN F ).
, .

- .
N -
,
-. , -

698

. , l a (-1, CCL3)
, NK- [Drake P.M.
et al., 2001].

.
NK-
, 2040%
, .
NK-, NK-,
.
.
NK- ,
. NK-
(CD56brightCD 16) . ,
NK- (CD56dim CD 16+).
, NK- ,
, .
HLA
,
. , NK- , ,
. NK-
Thl ,
, -, Th2 , , TGF-,
.
- TNF-a .
.
-
.
fgl2
, .
, NK- -

[Ashkar .. et al., 2000].
NK-
1520%
.
,
. , (-10,
TGF-pl), ,
. , ,
7-1, ILT3, MS-1,
.

.
( CD83+)

5.

699

-
2 .
- 10% ,
. -,
CD4+CD25+,
, ,
-10 TGF-lp. ,
, N -
,
- . 2,

,
.

HLA,
.
HLA- II ,
HLA-G lb. NK-
HLA-G
.
,
.
Fas-,
Fas (CD95) -.
.
( , CD46
-, CD55).


.
-

- ,
,
. ,
,
,
50% [Bibby . et al., 2004].
, Ureaplasma
urealiticum, , Listeria monocytogenes, Gardnerella, Mycoplasma
19, , [Peeb
les D.M. et al., 2006]. ,
,

, . , -

700

, ToII-IiJce
(TLR) ,
(TNF-a).
NK-
NK-, ,
. , TLR 4-
, ,
,
. ,
T N F -a, -6
-8 [Romero R. et al., 2004]. ,
,
,
, .
,
, ,

,
.

5.7. ,
,


.
.
, ,
. ,
, 20 2.

.
(13%)
.

.

()-.
() ,
, .
()- (
II, ), (
).
() - ,
, .

5.

701

, ,
.
, /
,
.

.

(. 5.10,5.11).

. , ,

(, )
.
.

, , ,
. 1114 .
()- .
, ()

[Manes ., 2001].
,
,
[Schafer G. et al., 2003]. ,
, -. , ()

.
,
, .

: ,
, .
.
,
. ,
. ,
, - ,
, , .
.
.
, , ,
, , ,
,

702

5.1
,


-S


.



(
) .
( ).
20 2
- 20

/-

20 2

20 2
20 0 2

5.11

-

.


.

/



-
.
-

. , -
[Ripalda M.J. et al., 1989].
,
,
-

5.

703

. , ,
, .



[L overro G. et al., 1996].
(, -), ,
,
.

,
. ,

,

[Jauniaux . et al., 2003]. ,

70
. ,
( , -
, )
[Vural P. et al., 2000].

, ,
. ,

,
, -
. ,
. , ,
, ,
, [Pavan L. et al., 2004].

.
,
, /. ,

. /
,
,
. /
,
. ,
, ,
. ,

.

704


()-.
,
- .

()-.
. ,
,
1- .
( ) [Deshend R. et al.,
2003]. ,

: F2
.

:
(),
, ,
F2 ,
[Peeble D .M . et al., 2006].

: , ,
. , , ,
,
[Vanderlie J. et al., 2004].
: ,
, , ,
, .


. ,
,
, ,
- , ,
, ()
,
p47phox, . . ,
[Stara
P. et al., 1994; Gulmezoglu .. et al., 1997].
, . . ,
, ,

, , ,
. (1000
400 ME ) 1622 .

(Peeble D.M. et al., 2006].

fnaea 5.

705

, ,
, , . ,
, ,
, .

5.8. ,

,
, .
,
, ,
.
, / ,
, .

, ,
.
- . ,
Fas-,
.

. ,
.
8-12 .
.

, ,
.


HLA-G . ,
.
.
,
,

.
, TGF-p, TN F-a,
(VEGR, PLGF).
,
.
,
, ,
, VEGF, PLGF.
11 "

______________ ________ _________

[ '" .

706

,
-1 , -6 T N F - a
. , -9 -J
c-fos c-jun.
, .

. NK- HLA-G
,
.
-. ,
, ,
, , . ,
H L A I ,
. ,

N K- [Quack .. et al., 2001]. , N K -

.
, - (
- ),
NK-.
, , ,
N K - , -2.
,
.
,
,
, .

5.9.


, , ,
.

- ,

(. 5.12).
, ,
,
, - .

.
, . ,
-

5. __________707

5.12

-1/

-6

-12
-16
-18
TNF-a/p

MIF (,



3
I31




III
III II



III III


I I III
III
( )
I




I I

I
-10



I
-13
(
I )
-IRA ( I


-1)

-
III


-
III

-8


-4



III

III


^

708

. 5.12

RANTES (

-,

-)

-1/2 /3 /4

(
)

III

III

III

III

-1, -6 T N F -a,
, .
-l a , , ,
, , -1
T N F -a , , .
-1, -6, -8 T N F -a
.
, , , , . ,
( -10, -4, -IRA )

.
,
.
( -8)

, -, ,
,
.
,
. ,
,
.
, ( ).
.

f- 5.

709


,
. ,
,
, ,
. ,
. ,

,
,
, TN F-a -.
,

,
, .
;
,
;
( ) -lji,
-6 -8, ,
. ,

.
,
.
. 20
,
.
,
. In vitro , PBEF (
--)
[Peeble D.M. et ., 2006].

.
,
, NK-kB.
, -2
( ),
.
,

/ .

2 F2a, , ,
.
(-1, T N F -a), ,
, . , -1

710

TNF-a 15-
(PGDH) ,
. , ,
.
, ,

:
(
,

(TN F-a, -10, -6)

I
I

j ^
( -4, -10
-IRA, TGF- )

. 5.7

fnaea 5.

711

(TGF-P, -IR A , -4, -10)


.

, ,
,
.
,
.

(. 5.7)

5 .1 0 .
(),
I , 0,5-3%
[Peebles D .M ., 2006].
(
), , ,
, . ,
/ . ,
50%
. , ,
.
.

. ,
-

.

2- [Negmann T.G. et al., 1993].
,
Th2
T hl
, . 5.13.
Th2
Thl. ,
, , . ,

-4 -10 [Chaouat
G. et al., 2004]. ,
.
2-
T hl - . , ,
,
Th 1-, , , -

712

-
5.13

-
,

-2, - TNF-a

-2, - TNF-a


-10

-2, -
TNF-a
-2, -
TNF-a

-2, - TNF-a

, 2-,
.
2-
-10 -4 - TNF-a
[Bates M.D. et al., 2002].

,
.
, ,
( , TNF-a
-308 -863, -10 -1082G/G - +874 )
[Peebles D.M., 2006].

.
-1
. -1 ,
, ,
, LIF.
-1
[Simon . et al., 1997]. -10
[Von
Wolf . et al., 2000].
-1 .
,
(. 5.14)
, LIF
-11,
-6, .
.
.
.
, -18,
-1 , T hl-
-. ,

5. _____________ 713

5.14
-1

-1

- 511

-3 1 /

2
G/A+3594

-1
-IRN

-1

WangZ.C. etal.,
2002

-1


Heifer LA etal.,
2001

Wang Z.C. et al.,


2002
Untied G. etal.,
2001

.
-18
, -18
.

-12, TGF-, - (-).
,
.
,
. -,
-,
, , . -,
, - ,
, .
,
.
uNK-. uN -
-1, -2 TNF-a. Thl-
uN - , ,
. in vitro -2
CD 16 uN - ,
, -4 , (3
-2 NK-, -2
[King A. et ., 1992]. TN F-a - ,
. -4, -6
LIF
. -1, TN F-a -6
-2 -9,
.

714

N K -,
, - ,
N K - HLA-
.


, .

5.11.



(85%).
, ,

( .).
(> 37 .) 10% ,
37 . 14% [ ., 2003].
,

.
.
.
.
,
,
. ,

[M cGregor J.A. et al., 1990].
,
,
.
,
. ,
,
, (. 5.15).
III ,
, IV

.

. , III
.

^ . _____________ 715
5.15




.003

IV
1,111,1V, VI
, , V, VI
1, III, IV, V, VI
I, 111. IV. V. VI

IV

IV, V

I, III, IV, V, VI



().
.


[Peeb
lesD.M. etal., 2006].
,

:
(TIMP) ,
-2 -9 ,
--9 , ,
.. .

. ,
, ,
, . ,

, ,
, .. ,
.
,
. ,
53, 1-2
. , 53
-2, . ,

.
,
,
.

716

5. is

-9

Ferrand .. etaT
2002

-8

Wang . etahp
2004

TNF-a

+17 (G)
-381 (G)
-308

Roberts A.K. etaf


1999

TLR4

896 G >

Ferrand P.E.etal.,
2002

19

, , ,
- , , . ,
,
,
(-1, -6, -8 TN F-a),
, ,
.

.
,
. ,
,
.
, ,
. , TN F-a , -lp
.

, ,
(. 5.16).
, , ,
.
5 . 1 2 .

,

, .
1,5 10%, 4% [Lopes-Jaramillo P. et al., 2001].
5.
15% .

(" 5.

7 17


40- XX . ,
, , .
.
19941999 . 40%, , ,
:
[Roberts S.A. et al., 1997].
,

70 .

.
,
,
.
,
,
: , .

.
,
, .

, , , .

. ,
,
.
5 .1 2 .1 .

( )
, ,
.
- (2200 . ..),
.
(460377 ..) ,
.
, 1513 .,
.
17- ,
, .
G. de Baillou (1538-1616)

.
XVII . ,
.

718

(17261763)
.
J.C. W. Lever 1843 . ,
.
, .
.
,
.
1827 . R. Bright , .
.
XIX .
, . W.A. Fraud 20-
.
,
,
, .
XIX .,
.
, , . XIX . .
- .
XX . ,
- .
.
,
, 1913 .
(W. Zangemeister).

.. (18101881);
.
.. ..
XX .
50- XX .
J A. Pritchard, .
,
, , .
- ,
. ,
, .


. 19992002 .
. Brenner, A. Elder (), R. Bick . (),
L. Heilmann . (), .. , .. ,
. . , ,

5.

719


[ .., .., 2003].
,
,

.
5 .1 2 .2 .

( 20 . )
(> 140/90 ..), (> 300 /)
. , 20-
6 . , .
,
-
, , ,
.
,
, 1898 . - .. ,
.
,
(
, , )
. , ,
, , , ,
.
,
, 7
.
HELLP- . HELLP-
(Hemolysis, Eleveted Liver enzimes, Low Platelets ,

) L. Weinstein
80- XX . HELLP- III
2448 ,
.

, , . : ,
- , , ,
, , -
, ,
(),
, , (),
.

720

5.12.3.

: ,
40 , ,
, , ,
, , , -
, , , ,
.
,
.
, .

. , . . ,
, , .
, , ,

.
3040%

. , ,
.

. , ,
25 .

, . ,
30% [ ..,
2003].
1984 . Chelsey.
Rath .
.
, HLA-G (Human
Leucocyte Antigen-G). HLA-G MHC-I (Major Histocompatibility
Complex-1),
1990 . Elis ., Kovats .
HLA .
HLA-G
,
NK-. , HLA-G .
G.F. Gensini (2002) ,
D ()

. (G894T) NO-
,
HELLP-, .

fnana 5.

721


TNF-a.

.
, 80%
,
54%,
16% [ .., 2003]. ,
90% . ,
, ,
, ,

.

.
( )
,
, ,

, .
, ,
, :
,

, .

, - ,
. .
.
,
: . ,

, . ,
III ,
. .
Jeffcoate
1959 . ,
, , . , 4 ,
. 3 .
.
, ,

;
.

722

,
, .
.

, . ,

.
,
,
.
,
. , ,
, .

,

. ,
, , ,
, ,
.
:
, , .
, ,
.
: .
, , .
.
N 0
,
.
N 0
, . , , ,
.
,
.
. ,
, ,
.
[Levine R.J. et al., 1997],
4 . , .
-

. J. Villar J.M. Bclizan (2000) ,

, .

5.

723

5 .1 2 .4 .

,
,

.
.
, , ,
.
, ,
,
, [Takacs P. et al., 2000].

, .
, ,
J.. Roberts . (1989). ,

.

, .
,

[Blake G.J. et al., 2001].
: ,
, , ,
, .
,
,
.
: , , .

. ,
, -
,
,
.

, -1, , , ,
, , .
,

.
:
-

724

(II , ),

(III ), -
(IV, V ).
,

, .

, ,
, .
( , ,
)
.
, :
, ,
III ,
.
, ,
- . . Becker
(1948) ,

.
. , . Cavangh
1977 .
a. uterina , a D.J. E d e r .. McDonald
(1987), -
3- ,
, , ,
.
,

,
.
,
, ?
,
.
,
.
( 510% ).
,
.

C3d. , III
. ,
, ,

5.

725

.
,
,
[Bretelle . et al., 2004].


. , G.P. Sacks
(1998), III ,

,
.

(. 5.17).
,
, CD1 lb
CD64 . ,
,
.
,
,
. L-
.

CD 14, .
, ,
HLA-DR,
.
.
HELLP-, , , ,
.
.. (2001)

-1, -6 TNF-a
, .
,
( -
, ),
.
5.17


CD11
CD64
CD14
HLA-DR

2-, ICAM-1
IgG

II

726

.
.

:
. ,
, ; -
,
.
,
(. 5.18).

, ,
.
,
.
:

?
. ,
.

.
(TNF-a) [Kirwan J.P. et al., 2002].

, , . 5.18

+
+
+
+
+
+
+
+
+


:
TN F-a

-6

-8

5.

727

,
.
, ,
. ,
. , ,
,
. ,

[Redman C.W.G. et al., 2003].
.
,
, ,
. , - ,
; ,
. , , ,
.
,
, .
, :
,
;

;
,

. ,
, X, .

, , III
, ,
.
J.A. Brosens W.B. Robertson,
, -
.
618- .

: ,

.
,
, ,
II .
.
.
,
.

728

3050%
[Granger J.P. et al., 2001].
-
.

.
2 ,
.

,
. ,
.


. ,
,
.
2+ -2- .
2+
[Hojo et al., 1999].
,
2+, ,
.
,
.
04+/08+, -
; CD4+,
CD45.
,
. .



. ,
.
,
.
.

.
. NK-, 2030%
, 1-3% [Redman C.W.G. et al.,
2003]. NK-,
, .

, . -

5.

729

,
.
,
,
,
.

.
.
Fas- .
,
. In vitro , ,

, 1, ,
-3 , ,
[ G. et al., 2003]. ,
, ,
XIAP , -3 .
,
, ,
.
,
,
. : albl,
(-9), t-PA,
HLA-G.
. , ,
, .
, ,

. ,
,
,
, . ,
.
TNF-a IFN- 10 [ G. et ., 2003]. , ,
, IFN-y TNF-a,

. , in vitro
. ,
, , Fc- TNF-a.


: ,
X, -

730

?
, ,

. , ,
,
, ,
. ,
. .

. ,
,
, , (
), (
) .

-,
.
Thl - 12- .
(TNF-a, -2, IFN-y) ,
(-4, -6, -10)
. -
. ,
TNF-a IFN-y,
-4 -10
I . , TNF-a
[Redman C.W.G. et al., 2003].
, ,
. ,
(TNF-a, -1)
ICAM-1 ,
[Mellembakken J.R. et al., 2002]. ,

.


-2, -6, -8, TNF-a [Olusi S. et al., 2000].
, TNF-a
55. , -2, -6,
TNF-a, TNF-a (sTNF-a) 55
I II ,
[Vince G.S. et al., 1995].
.

. , TNF-a
. -1,

5 .

731

,
,
. T N F -a ,
, iNOS,
T N F -a ,
, eNOS (Conrad . . et al., 1997].

,
. 14- 19-
T N F - a , T N F -a ,

[Granger J. P. et al., 1999]. ,
T N F - a
.
,
, . ,
D .R . . (2001) , T N F-a, -6,
-
. T N F -a
. F. Bretelle .
(2004), T N F -a
, . ,
,
in vitro .
,


,
,
. , -850/
T N F - a
[Heiskanen J. et al., 2002], 2-
- 1R A [Faisel F. et al., 2003], (-1082)
- 10, , ,
, . ,
+936 / VEGF [Shim J.Y.
et al., 2007], -308
/G T N F - a [M olvarec A. et al., 2008].
: NO-,
, ,- s F lt-1,
. ,
.
,
-
.

,
,

732

. ,
[Mailembakken J.R. et al., 2001].

.
.
:
?
. , ,

,
.
,
.
. ,
,
, ,
(, , ),
.
A. Barden . (2001)
, ,

. J.R. Mellembakken . (2002)

-
. ,
-
CD 11, CD1 , CD 11,
CD35 (CR-1), CD59 (complement protectin),
CD15s (Sial-Lewis-), CDlla,
CD1 lc, CD49d ( 4),
CD46 (membrane cofactor protein ) CD59.

.

, ,
. , CD35 ,
. CD46 4
; CD59 8 9 , ,
- .
, ,
- ,
CD49d CD88 ( 5).
- ,
CD49d CD88 .
,
. ,
.

5.

733


,
.
: J.R. Mellembakken . (2002) ,

, . ,
, . ,

CD 15s (Sial-Lewis), CD49d/CD29 (VLA-4), CD31 (PECAM-1) CD15s, CDllc (pl50,95), CD54 (ICAM-1) .
-8 G R O -a (growth-related oncogene-a)
. ,
.
.
-8
. ,
-,
.

sE- sP-,
. ,
- -, , ,
, . , sL-
.


.

, , . ,
,
(ROS) - (-), -
(ROO-) - (2-),
, : (20 2),
(1) - (ON 0 0 - ) .
,
, (,
, ) ( , ),
, , -, .
.

Clemesten Andersen 1964 .,
.

. ,
, , , -

734

,
.

/.

, ().
, . .
, .
.
/
.
,
,
.

, , ,
(, ),
, .
,
50% 48
[Roberts J.M. et al., 2003].

,
.
. ,
. ,
NF-kB
,
. ,
,

.
,
, ,
, . ,

,
.
.

,
, .

(- 5.

735

AT II,
()- , ,
.
(. 5.19).

, ,
.
. ,
,
13- ,
, .
in vivo
in vitro.
.

. 8-

,
,
. ,
8-.
8- ,
, ,
8- .
in vivo 2-.
, 2-
,
6 . . 6 .
2- , ,
[Barden A. et al., 2001].
5.19

; ,

; 8-


:


8-

736


, .
2-
. -, ,
!
-, , .

. ,
,
. ,
.
J.C. Chambers . (2001). ,
3 , ,
. ,
, ,
, ,
.

. , N 0
,
[Var A. et al., 2003].
N 0
. N0,
- (ONOO- ),
.

. 2 ,
(4872 ).
.

,
.
. P. Stratta
. (1994) .. Giilmezodlu . (1997),

. (1000 /) (400 /),
1622- ,
,
, 61%.
PA I-1 (
) PAI-2 ( ), ,
8-3nn-PGF2a ,
.
.

,
. -

5.

737

,
,
[Welch G.N. et al., 1999].
( 50%), II . A. Var
. (2003) ,
( 13,23 /),
(4,86 /),
412 /. ,
,
. , 18%
[ .., 2003].

- .
N 0 S- (SNOHO),
.
, .
20 2, .
N 0
. ,
NO-.
N 0 in vitro, in vivo.
.
,
, .
.
. ,

. ,
,
[Nelen W.L. et
al., 2001].
-, .
,
, . , M.Y. Tsai
. (2000)
, , .
,
.

: , HS, t-PA
.
(PC AT III) .
,
XII, \ .
24 -

738

,
, ,
. , ,
. Nappo . (1999),

.
,
.


. III
50%, () 300%.
,
(), , , ,
, .
,
. ,
,'

.
,
.
, ,
10- [Granger J.P. et al., 2022].
, ,
.

.

. ,
,
.
, ,
.
. , ,
.
,
,
.
,
, ,
-,
.
, , ; ,
,
, . -

ffi 5.

739

. , , -

.
HELLP- .
,
, .
. HELLP-
TNF-a
, .
, HELLP-,
, , ,
.
HELLP-.
: ,
?

.
, ,
.
,
. Nadjir, Sommers, de
Wolt, .
, , tunica
media , ,
, .
, .
,
, , ,
, . ,
,
, ,
.
P. Takacs (2000)
. In vitro ,
,
NF-kB ICAM-1 .

N -. -3-

3 .
ICAM-1,
,
, ,
, , .
ICAM-1

740

.
ICAM-1, 18- , [Djurovic S. et al., 1997].
NF-kB ,
, . NF-kB
,
, , .
NF-kB ,
,
, .
.

.

, ,
. ,
. J.A. Hill 1986 .
,
(19% ), (36% ).
R. Mittendorf . (1996) ,
50%.
.
-2, .

.


, .. .
, , .
.

.

,
.
. ,
,
. , in vitro ,

[Levi . et al., 2000].
,
.
,
, .

.

5.

741


.
, ,
[Bretelle . et al., 2004].
, . -, ,

. -,

. ,

.

5 .1 2 .5 . .


. , 5- ,
(),
16- .
, . ,
80%, 200%,
1000 .
-- (), , , ,
, I
. , ,
I , II
III .
(

),
,
(NO, PGI2,
EDHF ). ,

.

.

;
,
, , PGI2
.


. ,

7 42

.
,
.
.
AT II .

. W. Visser ..
Wallenburg (1991)
.

. .. Schobel .
(1996),
.
, , ,

. ,
|32- [Aune . et al
2000] .


, P G I2 NO,
-1, ,
. ,
,
, , .
- .
.
, PC,
PS, AT III.

. , PAI-1,
, , , PAI-2
. PAI
.


, , vWF.


.
19- ,
24 . [Roberts J.M. et al., 2003].

. ,

. CFN- , -

f 5.

743


, ,
. cFN
II
, .
PAI,
.

,
.
ICAM-1, VCAM-1,
.
ICAM-1 VCAM-1 3-15 .
. 1-1
18-
[Djurovic S. et al., 1997].

.
. , ICAM-1
, , .
, ICAM-1 .


.

.
(PGI2) ,

.
,
2,3--6--.. ,
PGI2, , AT II
-1
[Janowiak .. et al., 1998]. -1
() [Habermehl D.A. et al., 2000].
, PGI2
. ,
. PGI2

20 .
. ,
--P G F la , .
--PGFla
[Suzuki Y. et al., 2005].
. , PG12

, ^

744

. , (
)
TXAj.
,
, P G I 2 .
N 0
N 0 ,
, ,
- .
NO ,
. , 17- NO [Bucci . et al., 2002).
GMP NO [Sladek S.M. et al., 1997J. N 0
D.J. Williams . (1997)
, N O - N - 6 -*
p.- (L-NMMA)
, . . P . Conrad .
(1990) N 0 .
NO-
, , , ,
.
, N 0
, . .. Belayet
. (1998) NO-
, .
,
N 0 , .
, N 0
[Suzuki Y. et al., 2005; Redman C.W.G. et al., 2003]. :
N 0 PG I2 ,
?
N 0 PGI2,
. , N 0
,
. , ,
.
, , , N0
. ,
P G I2.
, N 0 NO-
, N 0 . G .P. Grange .
(2001) ,
N 0 ,
NO-.
- N 0 ,
N O - .

5.

745

, ,
.
NO . , S.T. Davidge . (1995) in vitro
, NOS
, . . Nobunaga
. (1996) , , :
, .
N0

. Y. Suzuki . (2005)
, N 0
, .
, L-NMMA

, [Knock G.A., Poston L., 1996].
, N0
PGL, .
(EDHF).
,
, EDHF ,
450. , ,
N 0 PGI2 , EDHF .
--

, ,
II.
.
.
, , , , . 1973 . Cant ,
AT II,
, 2- . ,

.
AT II
. , AT II
N 0 PGI2 2 [Granger J..
etal., 2001].
II , ,
. ,
,
. -

. ,
, AT II .
AT II,
.

746

70- XX .


-
,
,
.
-1
-1 (-1)
. ,
,
. 23 ,
.
.
-


[Alexander .. et al., 2001].

a. uterine
[Granger J.P. et al., 2001].
-1
. -1
, . -1
,
.
-1
. ,
,
. , -1 .

. , -1
.
, ,

,
AT III .
, ,
.
- ,
,
, .
PARs.
, G-npo.
N -

^ 5.

747

, PARs.
pA R s: PAR-1 ; PAR-2
; PAR-3 .
-1 PAR-3 ; PAR-2, PAR-1 TFVila .
PAR
, , ,
, NO, PAF, -1 12. PARs
.
J.R. Steinert . (2002) ,
PARs
.
PAR-1
, PAR-2
.
PAR-2
, (TNF-a,
-lp, -6, -8), ,
. ,
PAR-2
.
, PAR-2
[Saifeddine . et al., 2000].
, PAR-2
,
[Wang Y. et al., 2002]. PAR-1
, , .
PARs . ,
.
, PARs

, ,
.


.
.
,
,
,
(VEGFRR-1) ,
, sFlt-1 ( fms- ).

. VEGF ,
,
, VEGF . ,
sFlt-1

748

, ..
[Kabbinavar F. et al., 2003]. sFlt-1

[Maynard S.E. et al., 2003].
VEGF ,
VEGF. sFlt-1
sFlt-1, , ,
. ,
,
40 . , sFlt-l
[Belgore F.M. et al., 2000].



.
II .
, ,
.
3- .
,
. ,

.
, ,
-1 (
) [Granger J.P. et al., 2001].
- 14-

. -
, -.

.
-
N F-
.
(TN F-a, -10),
(-8, -1), , .
-
, .
5 .1 2 .6 . -


,
,
HELLP-. , ,
.
.

^ 5.

749

.

-.
-
F.W. Page D. McKay (1953),
.


-,
, - ,
.
-
, .
.

, , , ,
, ,
,
-.
,
.
, ,
, ,
,
.
,
,
, . -

- .
-
. ,
, .

. ,
,
.
,

. ,
,
.
,
,
- .

-

750

.
.

. -
, ,
, ,
.
, , , .
, .

,
.
;
.
,
.
.

. ,
.
.

.
, , ,
, .
,
,

. ,
2 ,
8 , .
-
:
;

( ) ;
,


.
, 10% ,
100%
.

' 5.

751


. ,
( , FI+2),
,
, .
: AT III PC.
, -,
-. -
.
() D-
- .
,
, -.
(> 20 /),
(> 35 /) AT III
(< 45%). , ,
.

- -
.
.
(, HELLP-)
,
, .
,

-
.
5 .1 2 .7 .

-
?

60- XX ., ,
, ,
.
L.S. Chesley, 930 . 47
, , ,
, .
,
, - . L.S. Chesley
, ,
,
, - .
, . Sibai (1986),
L.S. Chesley .

752

, - ,
, , .
- .

2,35 , 2,24 , 1,65
1,53
. ,
, , ,
, , ,
. ,
2,35,5 . ( 55%)
(
28 .) . ,
, .
, ,
.
,
-
.
.

, , ,
.

, ,
,
, .

, : , , , .
, ,
,

.
:
-
(II ,
),
(III ),
- (IV, V ).
,
.
, ,
, ,
( ,
), () ,
- (. 5.8).
:

5.

753

, -

.
, :
,
;
*
;
,

. ,
. ,

_________ _________

, , ,
-, ,
_________________ _______________

. 5.8.

754

- *
. , 8,
, ,
,
, .

,

.
,
,
, PAI-i
.

,
.
,
, ,
,
.
, .
, ,
,
, .


, .

-,
- ,
.
-
, .
. ,
.
( -
, F1+2, , , ).
,
, , . ,
,
,
, ,
. .
,
, TNF-a, -

/ 5 .

755

,
,
IAlexander .. et 2002].
, ,
. ,
, L. et al., 2001].
Th--,
,
[Saito S. et al., 1999].
.

, ,
. ,

, ,
.
,
(. 5.9). ,

, , ,

1
:
11
1


(
( , !

)
,
)

1
1

. 5.9.

756

, , ,
.
,
TNF-a. ,
- .


, ,
.
: ,
, , .
, ,
.

,
, ,
- . ,
- ,
. --
, . TN F-a. TF,
(TNF-a,
IL-ip).
- . ,
,
.
, , ,
. ,
A. Vignoli . (2006) ,
TF
,
.
5.10
.
,
.
,
, . ,
S. Bretelle . (2004),
,
,
, .

. ,
-

f-fjpaa 5.

______

757

. 5.10. :

. , ,
,
.


.
:
1. :
-- ;
TFPI.
2. :
- ;
( TNF-a);
TF .
3. :
(t-PA) TFPI;

vWF.

5. 13. H E L L P -

1954 . Pritchard . ,
,
. 1976 . Pritchard 95 , 29%
, 2% . Goodlin
16 ,
, , . .
. HELLP-
(Hemolysis, Elevated Liver Enzymes, Low Platelets)
Weinstein 1982 .
,

758

,
.
HELLP- ,
, 220%
(3,424,2%) (7,9%) .
III ( , 35 .)
.
, .. Sibai . (1993), HELLP-
(30% ), (70%).
. HELLP 7 ,
48 .
HELLP- ,
25 , .

. HELLP-
, ( 2,2 ) - .

, , ,
, HELLP- , ,
.
, ,
, , -.
HELLP-

(. 5.20). :
, , , , , , ,
.
(86% ),
(86%), (67%).
, , ,
.
, , -
, .
, .
HELLP- .

, , .
HELLP-
.
HELLP- (
),
,
(), .

. -

5.

759

5.20
HELLP-

,
,

1
,} . * . 1

,
.
() .
,
.
.
-

( )
- ( , ,
).

,
.
, ,
75% , -
.

,
, .

(
, ..).
, HELLP-.
, HELLP-
1,8%, 58-70%.
HELLP-
-

760

.
.

.

( 24-48 ),
HELLP-. , ,
HELLP-, -
.
, ,
, HELLP-
(42%).
HELLP. HELLP- , ELLP- ( ). HELLP . M.G. Van Pampus . (1998)
(, ,
) 10% ELLP- 24%
HELLP-. ,
ELLP- HELLP-.
(, ,
) HELLP- 4060% . ,
75% HELLP- 160/110 ..,
15% 90 .. 9%
, 16%
[OBrien J.M. et al., 2005]. , ,
HELLP-
.
.

HELLP-: -, ,
, , ,
.
R.S. Egerman . (1999),
HELLP- 11%, ,
.. Sibai ., 37%.
, (81,6%),
(31,6%). .. Eeltnik
. (1993), 87
HELLP-, 10% ,
10% 1- . ,
HELLP-, :
(1136%), (1214%), (10%), -
(11%), (58%), 34
- (36%), -
(51%).
.

^ 5.

761

V HELLP-
. D. Abramovici
. (1999), 269 ,
HELLP-, ,

HELLP-
.

HELLP- .
,
,
, .
, HELLP-,
.
. J.R . Barton . (1992), 11
,
HELLP- ,
- .

. Minakami . (1988), 41
HELLP-,
() HELLP- . ,
HELLP- .
,
HELLP-
. ,
HELLP- . ,
III . ,
HELLP-, ,
.

HELLP-
. HELLP-
.
HELLP-
, ,
.
,
. , HELLP-
,
,
. , HELLP-
. J.R. Barton . (1991),
HELLP- . ,

762

- Knuu,1Kr

. , HELLP-

.
.
(-6, T N F -a, -1 .),
.
HELLP-
.
, HELLP-
.

, ,
, -
^ .
,
. HELLP- . , - 38%
HELLP-
HELLP-: ,
, ,
, . HELLP- ,
,
, , .
,
, HELLP-
.
.A. Sullivan . (1994), 81 ,
HELLP-, 23%
, 19%
HELLP-. .. Sibai . (1995), Chames
. (2003) HELLP-
(46%). .. Sibai .
, , ,
, HELLP-.
HELLP-

. ,
. Krauss . (1998), , HELLP-,
-R FV Leiden.
D.
Schlembach . (2003) , FV Leiden 2
HELLP-
. , HELLP-
. G. Moessmer . (2005)
ELLP-
20210.

IjiQgQ 5.

763

. ,
, , . HELLP-
(02-0,3%).
, HELLP .
, ,
( , HELLP-)
. , D. Schlembach . (2003),
,
.
Altamura . (2005) HELLP-,
, MTHFR
. ,

. , D.O. Wiebers . (1985),
15 44 10,7/1000 000,
13 .
( ,
)
,
: HELLP-
, , , -, .
, HELLP-
, ,

,
, .
(), HELLP-
,
(), - (),
.
. ,
, , ,
, . ,
HELLP- ,

HELLP-. . Koenig . (2005)
, HELLP-,

,
. , HELLP-
. HELLP-
.

HELLP- :
1. (, ).
2. ( ,
).

764

3. 1,2 /.
4. 600 /.
5.
(ACT) 70 /.
6. ( 100109/).
7. :
+k ;
;
;
-;
AT III;
AT IIIJ
,
PC (57%);
.
8. .
9. .
HELLP-
0,6 /.
Martin . (1991) 302 HELLP- ,
,
: I 150100 109/, II
10050 109/, III 50 109/.
HELLP- ,
,
, ;
HELLP- ,
. (
), , , ,
. ,

, , . 1991 .
R.C. Goodlin 11 HELLP-
, ,
, , ,
. , ,
HELLP-
.
HELLP-
(. 5.21).


,

.
. ,

fjisBB 5'

765

5.21
HELLP-


, , , , , ,
,
-
,

ACT, , , , (),

, , (
)

, , ,

, .

.

, .
HELLP-
,
.

, HELLP- .
, ,
-; -

.
HELLP-
.
:
;
;
;
;
34 . ;
.

, ,
, .
,

. -

766

,
,

-
.
.


: ,
. ( < 70 /).
40 000/
.
,
, , .
(. 5.22).
-

100%
,
.
HELLP-
75 3,424,2%.
5.22
HELLP-



6 10%; 5%;

< 70 /

40 000/



-


, (

)



160/105 .. ,
, ;
( 180/110 ..),
( )

AT III ( 1000-1500 /,
1000-2000 /,
2000-3000 /), ,

gg 5,

767


, ,
,
. R.C. Goodlin . (1978), Clark . (1986)
, (10
/ 12 ) ( ,
, , ).
E.F. Magann . (1994), .. Yalcin . (1998),
. Isler . (2001) ,
HELLP-,
24-48 ,
-
. .. Isler .
, .
,
,
.
, 24-48
, , . ,

, ,
.
HELLP-
10 / 6 ,
6 / 6 . HELLP- ( 20 000/, )
20 , 4- 6 .

(4- / 12-
10, 10, 5, 5 )
. J.N.Jr. Martin . (1994),

.

- HELLP. , , ,
, HELLP-
24-48 ,
[Baxter J.K. et al., 2004].

24 [OBrian J.M. et al., 2005];
.
72
[Baxter J.. et al., 2004].
, HELLP ,

768

.
HELLP- .
, HELLP-,


.

5.14.


,
,
60-70%
[Stafford I. et al., 2007].
,
(. 5.23).
.
.

.
, , ,
, , ,
, (, ).

1941 . Steiner Luschbaugh. , .

, 5.23

, , , , , , ,
, , ,
,

fliflpe 5;

769

15%-
. 80%
# [Tiffnel D.J., 2003).


. ,
,
. IX) - ,
.


,

.
. , in vitro
, ,

.

.
,
,
[Schoening A.M. et al., 2006].
,
,

(. 5.11).
/ ,
,
-, , , .

,
, , , ,
, (
, , , , ). ,

(T N F-a, -1, -6, -8) ,
,
[Peeble D.M. et al.,
2006].
,

. ,

,
25 -

77

(

()

(IgE)

:

,
, ,
| )


(TNF-a, -1,
-6,
,
, ,
2)

I
I

. 5.11. ,

,
.

, - ,
, , .

,
.
.
,
,
- ,
. ,

5.

771

- .

,
,
. ,

.
5 .1 5 .


,
, 1997 .
R. Gomez . , -6,
, 11 /

.
,
, .
, ,
Thl-, Thl [Matsuoka .
et al., 2001]. ,

[YoneyamaY. et al., 2003]. ,
.
,
. ,

-6 > 11 / .

,
, ,
- .

.
,
[Yon .. et al., 2000]. . .
,


[Peebles D.M. et al., 2006].

-9
, IV ,
, .

772


, -, ,
, , , .
.
- ,
, , , .
,
. 2/ 3
, 7% .

,
. ,
, , ,
[ S.M. et al., 1995].
, ,
, .
,
,
. ,
TLR2
TLR4 [Peebles D.M. et al., 2006].
.
,
, /
[Yoon .. et al., 1999].
< 5
-6 ( ),
-6, -4(3 T N F -a
( )
,
. .
,
, . ,
.
,
, .
, ,

. ,

[Parker .. et al., 1994]. ,
, ,
. ,
.
,
.

5.

773

,
, ,
. -

. ,
, .
,
T N F -a, - M IF (, ).
,
, ,
, , . , ,
CD 14 , .
- TLR4
NK-kB,
, TNF-a -.
,
-TNF, -MIF -10
.
III ,
-TNF-a
,
TN F-a - |Abraham . et
al., 1998; Kraut E.J. et al., 1999].
(, ),
,
,
, .
:
.

.

.

, ,
.
. ,
> 1500
25-30 , [Hagberg .
et al., 1989]. ,

. ,

, NO-, ,
[Nelson .. et al., 2005]:
NO- 922 /G (OP [ ] = 3,0;
95% [ ] 1,46,4).

774

V II [-323] ( = 2,7; 95% = 1,16,5).


675 4G/5G 11053 G/ ( = 3,2; 95% = 1,2-8,7).
: -26- ( = 2,1; 95% ==
= 1,0-4,6).

.
[Wu Y.V. et al., 2002], ,
(-6, -8, TNF-a) -9
[Yoon .. etal., 1999].
,
, .

.
;

. , TN F-a
.

TNF-a -lp,
,
.

,

.

,
, ,
[Yoon .. et ., 1999;
Watterbeig K.L. et al., 1996].
,
, , ,
.
(-1,
-6, -8, TNF-a, -1, -8, ) .
( , TNF-a, - l p )
, , ,
. ,

. ,
,
. ,
, -2, MAP-
NK-kB, . ,
,
, ,
. ,

5.

775

( - 1, TNF-a) , [Allport V.C. et al., 2001].



,
.


. , 14 -9
1607 1G/2G -1 (
)
[Ferrand ..
e ta l.,2 0 0 2 ].

, ,
, , ,

,
.
,
,
,
,
(-10), MIF,
,
.

5.16.

-
.

.
, 2535%
. 60
43%.
, ,

, ,
- ,
, .
, ,
.
.. Reaven,
1988 . X,
,
( ), . , -

776


.

(1998):
() ;
;
;
();
2;
;
;
;
;
.
.
, , , ,
, ,
, , , : ,
,
1 (PAI - 1).
,
:
1) > 102 ( ), > 88 ( );
2) > 150 /;
3) < 40 / ( ), < 50 /
( );
4) 130/85 ..;
5) >110 /.
,
, -, -
(,
II, , T N F -a, PAI-1)

.
.
,
.
, , ,
.
(TN F-a, -1, -6), , ,

. , IL-6
.
,
.

5.

777

, .
, TF PAI-1,
.
, ,
, , , ,

(. 5.12).
(
VII
), ,
.
, ,
,
PAI-1, .
PAI-1 60%
,
. ,
. PAI-1 , ,
, , . ^ ^

:
,

JYL

----------~ 7


, , HELLP-

. 5.12. ,

778

PAI-1 . , PAI-1
, PAI-1
.
PAI-1 , , -1,
. ,
PAI-1 .
4- (4 G /5 G ) PAI-1
PAI-1 . 4G- PA I-1,
50-.


.
-
.
, ,

.
: ,
, , ,
.
,
,
.
-1

-1 . ( -1, )
,

.
, .

.

100% ,

675 4G/5G -1 90% , 85%
4G /4G -1. [ .. ., 2006]
,
,
, ,

. ,
G894T [Hsieh .. et al., 2008],
T N F -a [M aumus S. et al., 2007].

- 5

779


,
,
,
.
,
.

(. 5.24):
1. .
2. .
,
,
,
. ,
.
5.24


( .. ., 2006)


'



1 (
MTHFR 677
4 )
MTHFR
677
6,
,

5 0 -7 5 /
-6

(2850 ) 1 /
(
/
-)
+ / (?)
-

II, III

+ .
+

,

(

),
.



12-20-


/

-, ,

.


24-




10

780

, ,
(. .: .)

. .
, : .... -
. . ., 2003. 268 .
. ., . ., . ., ..
/ / . . . 1999; 2:23-8.
.., . .
. ., 2003.
.., .., .., . .
. .: ,
2006. - 477 .
..
/ / . . . 2000; 1:214.
.., .., JI.H.
/ / . . 2000; 3:48-51.
.. ., 2004.
..
/ / . . . 2004; 12(13).
.., .. . ., 2000.
- .., .., . ., ..
()
// . . . 2001; 1:5861.
.. , , HELLP-.
, 2003.
Abraham ., Anzueto A., Gutierrez G., Tessler S., San Pedro G., Wunderink
Dal Nogare A., Nasraway S., Berman S., Cooney R., Levy H., Baughman R., Rumbak ., Light R.B., Poole L., Allred R., Constant J., Pennington J., Porter S. Double

blind randomised controlled trial of monoclonal antibody to human tumour necrosis


factor in treatment of septic shock. NORASEPT II Study Group / / Lancet. 1998
Mar 28;351(9107):92933.
Abraham E., Anzueto A., Gutierrez G. et al. for the Monoclonal antibody to human
tumor necrosis factor alpha (TNFMab) in the treatment of patients with septic shock.
NORASEPT II Study Group / / Lancet. - 1998; 351:929-33.
Abraham E., Reinhart K., Opal S. et al. Efficacy and safety of tifacogin (recom
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J.A.M.A. - 2003; 290(2): 238-47.
Abraham. E. Why immunomodulatory therapies have not worked in sepsis / / In
tensive Care Med. 1999; 25:55666.
Alexander B.T., Cockrell K.L., Massey M .B., Bennett W.A., Granger J.P. Tumor
necrosis factor-alpha-induced hypertension in pregnant rats results in decreased
renal neuronal nitric oxide synthase expression / / Amer. J. Hypertens. 2002
Feb;15(2Pt 1): 170-5.

pa /.

781

Alexander . ., Rinewalt A.N., Cockrell K.L. et al. Endothe-lin-A receptor block


ade attenuates the hypertension in response to chronic reductions in uterine perfusion

pressure / / Hypertension. 2001; 37:485-9.


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50 , 40 [Rosendaal F.R.
et al., 2003].

. ,

MTHFR 677, , II , ,
OK III ,
, , ,
, .

8 04

,
.
RATIO 24
VIII IX,

.
6.2.5.


,
.

,
.
-
24 (. 6.3).

. Oger 1999 . (RR = 2,1)
(. 6.4).

. , . Grodstein . (1996),
, 0,625 ,
, 1,25 (RR = 3,3 6,9 ).
65%,
.
, ( + ) 60% , .
.
. Cushman . (2004), 6069 ,
-, 4 ,
70 7,5 .

(. 6.5).
, ,
,
,
[Brenner B.R. et al., 2002].
,
EVTET [Hoibraaten . et al., 2000]
, , , ,
: 10,7%
2,3% -.
.
, ,
.
,
FV Leiden (. 6.6).

6.

805

6.3
-

100 .
,
/

3,6

9/32

3,5

11/27

2,1

8/14

1980-1994,

1993-1994,

Grodstein F. 1976-1992,
Nurses Health
etal., 2001
Study,

JickH. etal.,
2000
Daly gjj etal.,
1996

6.4

100 .

(
/ )

HERS [Hulley S.
etal., 1998]
WHI (Womens,
Health Initiative)


( 0,625 +
+ 2,5 )

1993-1998

2,66

230/620

1993-2002

160/340

0,625
Beral V. e ta l.,
2002

1993-2004

2,11

2,07

2,13
1,34

2002

2,16

6.5


WHI

Nelson . .
\

3,6
2,26
1,67

2
3
6
1
1

0,9
3,49
1,91

806

6.6

FV Leiden
1

FV Leiden

1F.R. Rosendaal
. (2002)

..

(D.M. Herrington
[ . (2002)

+
+
-

.. .

3,2
3,9
15,5
3,7
3,3
14,1

+
+ (

G20201A
, , [Rosendaal F.R. et 2002].
, . Cushman . (2004),
MTHFR 677, XIII Val34Leu
PAI-1 4G/5G.
G. Lowe . (2000),
, IX, -R, AT III, PC,
4-
, .
,
715% , ,
.
27 ,
. 75%
( , , ). 100%
(
20% , 80%). 49%
: .
. 6.7.
, , ,
.
,
( , , ,
, ,
, ,
),
. ,
HERS WHI
,
, .
, ,
HERS WHI ,
,
.

f- 6.

807
6.7


( = 27)

FV Leiden
G20210A


12(44,4%)
10(37%)
5(18,5%)

GPIa 807/
GPIIIa 1565/
GPIba 434

7 (25,9%)
9 (33,3%)
2 (7,4%)

PAI-1 4G/5G
t-PA I/D
I/D
APC-R

19(70,3%)
9 (33,3%)
10(37%)
15(55,5%)

6.2.6.

,
80- XX ., .
-
, .
,
Nurses, Health Study (NHS)
Heart and Estrogen/Progestin replacement Study (HERS) Womens Health
Initiative (WHI).

- .
Nurses Health Study (NHS) (1976-1996)
86 . (
3459 ) .
: 40%
61%
.

80% ( ,
< 25 /2, , ).
Heart and Estrogen/Progestin replacement Study (HERS)
-
(1993-1998) 2763 (
66,7) .
: 0.625 + 2,5 .

808

:

;
;

;
2,7 .
ERA (Estrogen Replacement and Atherosclerosis) ,
309 55 30%
0,625 0,625 +
2,5 3 .

.
Womens Health Initiative (WHI)
-

5079 .
. 0,625 .+ 2,5
16 608 . 8,5
5,2
.
(0,625 ). 10739
. 2004 . -
.
,
29%, 41%, 2 ,
26%;
23%.
HERS, WHI ,
American Heart Association
.
,
, ,
(. 6.8).
NHS,
6.8



- 12 ,
1993

Scarabin .
. (2003)

0,69

0,94
1,23

HERS

0,99

WHI: +

1,29

1,44

0,91

1,39

6.

809

. ,
40% , .

.

.
F. Rosendaal . (2002),
30 ,
.
G20210A 1-2%
,
. F.R. Rosendaal . (2002),
, , G20210A 3,2 ,
. 43
.
G20210A .
FV Leiden G20210A
, ,
.. Psaty . (2001), G20201A
11 .
FV Leiden G20210A
2 [Seelig M.S. et al., 2004].

, .

6.3.


6.3.1.


.
-
.

. -, , ,
,
.
,
. ,
. .

, -

810

, , , ,

, .
- . ,
,
, -
.
6.3.2.


,
.
() , . 6
, 8 [Lu . et al., 2002].
/ /F
AF-1 AF-2 .
-
. D , ,
.

.
, 1996 . G. Kuiper .
, .
, , , , ,
, , , , , , ,
. 477
54 200 . AF-1,
- 96% , 53% [Mendelsohn .. et al., 2004]
(. 6.1).
,

- -

AF-1

30%

'IH ft

96%

39%

. 6.1.

18%

53%

6.

811

.

. ,
[Raghvendra . et al., 2001].
, -
. ,
. ,
G. . (2002), ,
, ,

.

.
- . -,
- ,
,
(ERE-estrogen responsible element)
.
500 ,
,
.
N-myc, -, c-ras, c-fos [Raghvendra . et al., 2001].
,
(EGF) .
EGF,
-1. EGF, ,
, , ERE-.
,
,
(NF-kB, -1). , . Gaub . (1990) ,
c-fos c-jun
ERE- .

. ,
.
() .
( Ras/Rho, -3-, , B/Akt), ,
,
.

.
,
, , ,
.
, .. 2-
4- .

812

450 (CYP450), CYP1,


CYP2 CYP3 [Raghvendra . et al., 2001].
, CYP450
,
. 2- 4-,
, ,
.
,
, ,
-0-, ,
. 4-
, ,
, . , 4-,
2-, . ,
2-
4-.
40%
() .
, ,
.
. 2-
4-
, .
6.3.3.


.
,
NO, PGI2, cGMP, cAMP, EDHF (
) AT II, -1,

in vitro
in vivo ,
, , . , , N 0
. V. Guetta . (1997) ,
17-

, NOS .
5
[Sarrel Ph.. et al., 1999].
, ,
,
,
, [Williams J.K. et al., 1992].

6.

813

, 20
- [Collins P. et al., 1995]. ,

17-.

.
,
.

, cGMP
N0 .

, .
G. Rubanyi . (1997)
.
, N 0
.
2000 . [Simoncini . et al., 1999; Men
delsohn .. et al., 2001]
.
, , eNOS Hsp90.

85 13-, Akt,
, , eNOS N0
[Koh . . , 2002].
,
- +-,
2+ N 0 .
.
N0,
MAP- , . .
NO [Raghvendra . et
al., 2001].
,
.
N 0
.
EDRF eNOS
.
, N 0,

. , - . ,
,
.

814

-1
. ,

-1 [Sarrel Ph.M.etal., 1999].

. , 17-

-
[Jiang . et al., 1991].
L- +-,

.
,
+-. , +-
EDHF, .
,
.

eNOS,
,
[Tracy R.P. et al., 1997].
N 0 , , , .
,
nNOS eNOS, iNOS . 5*-0
eNOS ,
N 0 .
N 0
,
[Rosselli . et al., 1995].
.

.
N 0
, , ,
.
6.3.4.

in vitro
,
,
.
, , ,
,

.

6.

815

,
. PDGF (
), , -1, IGF-1, FGF- ( ), , , .
,

: PDGF, , -1
MAP-,
-, c-fos, .
IGF-1 FGF-

.
.
,

. 1-182780,
-
[Raghvendra . et al., 2001].
NO ,
,
.
.
: N0 [Elhage R.
et al., 1997] ,
[Naschimento C.A.D. et al., 1999].
-
, .
G. Li . (1999), in vitro
.
,
ICI-182780.
2- , N 0 ,
, , ,
,
.
,
, . ,
IC I-182780
,
50 ICI-182780 [Koh ., 2002].
,
.
, ,

816


.

VEGF FGF-p [Raghvendra . et al., 2001]. ,
- FGF-p
. , -
, , , .
, -
. , FGF-p,
,
.
iNOS N 0.
,
FGF-p. ,
iNOS, FGF-p
.
in vivo , VEGF
. , D. Weatherford
. (1996) VEGF
. VEGF
--
. VEGF
MAP- VEGF-
. , VEGF
.
N 0 VEGF,
NOS .
,
,
. ,
, TN F-a [Spyridopoulos et :,' 1997].
,
.
,
.
6.3.5.


:
, (),
.
(),
/. 30 3,03,5,

6.

817

4,07,0. ,
.

: .

; ,
.
22% [Shneider H.P.G. et al., 2005].
.
, ,
.

. PEPI,
, 15%
2025% [Cuhman . et al., 1999].
R. Lobo . (2001)
.
,
[Luyer P. et al., 2001].
ApoAl,
,
. .
, , ,
, .

,
. ,
N0, .
. Subbiah . (1993), in vitro
, ,
,
.
in vitro
.
. , !. Wilcox . (1997) . Sack
. (1994) ,
, J. McManus
. (1997)
. ,
,
.
, 3 ,
[Koh ., 2002].

(2- 4-),
,
, ,
N 0 PGIr

818

...

,
-
. in vitro,

,
.

.
.
HERS
, 1018%. ,

,
, ,
.


.
,

.
:

,
,
; ,
;
,
;

,

;
(; ,
, ..),
,

;
, ;
(
, , ), ,

;
.

pafi

819


.
6 .3 .7 .

,
,
.
,
, -
, ,
- .
-
.
17-
. , 17-, ,
. , - . Modena . (1999)

17-
18 . (Estrogen and Prevention of Atherosclerosis
Trial) [Hodis et al., 2001] , 1 /
,
, 130 /.
17-
. ,
-R. ESPRIT (Estrogen Therapy for Prevention
of Reinfarction in posmenopausal Women), 1017
50-69 , , 2
[Khan .. et al., 2000].

. ,
,
,
, .
,
,
. , 10 ( 17-,, , 17-, 17-, 17- .), 17-
[Heckbert S.N.L. et al., 2004].
. , -
, , . ,
,

820


.
, :

.

.

.
, .
.
,
, . (
-), ,
. ,
J.K. Williams . (1994), 50%
- ,
.

. ,
[Brenner B.R. et al., 2002].
,

.

[Lobo R.A. et al., 1994].

,
, , (. 6.9).

,
, [Herkert . et al., 2001].
( 19-), 3 ,
.
. Adams . (1997), , ,

,
.

[Alexandersen P. et al., 1998].
,
. ,
,
.

, -

(- 6.

821
6.9


+
+
+

- -
+
(+)
+
(+)
+
(+)

:
+>> ;
- ;
(+) .

. ,
[Hofseth L.J. et al., 1999].

.
17- ,
.
- ,
1 (1GF-1) IGF 3.
, , ,

.
.
, ,
HERS WH1
. ,
- ESPRIT
(Estrogen in the prevention of Reinfarction Trial, 2003), 1017
5069 , : 2

.
,
.
.

.
6 .3 .8 .

,
. , , ,

.

822

,
,
, , ,
A (SAA), VIIF, t-PAPAI-1.
, . , ,
-. ,
. , -
IL-6 .

, ,
, ,
, ,
.

, ,
(
, , , 2).

- (. 6.10).

.
,


.
6.10


( Danesh ., 2004)

vWF

t-PA-
-
SAA
ICAM-1

-
-

7213
7068
7229
4386
3770
3969
2119
1535
1057
1307
1192
832
627


( 9 S%)
1 ,8 (1 ,6 -2 ,0 )
1 ,4 9 (1 3 7 -1 ,6 2 )
1 ,4 (1 ,3 -1 ,5 )
1 ,3 3 (1 ,2 2 -1 ,4 4 )
1 ,5 (1 ,3 -1 ,7 )
1 ,2 3 (1 1 4 -1 ,3 3 )
1 ,4 7 (1 ,1 9 -1 ,8 1 )
1 ,7 (1 .3 -2 .2 )
1 ,6 (1 .1 -2 ,2 )
1 ,0 2 (1 ,8 1 -1 ,2 9 )
1 ,2 1 (0 ,9 5 -1 ,5 5 )
1 ,1 6 (0 .8 7 -1 ,5 3 )
1 ,1 8 (0 ,6 3 -2 .2 1 )

f- 6.

823

, in vivo, in vitro,
, . ,
,
(. 6.11).

,
,
. -

, [Sakai .
et al., 1997]. -
,

[Blake G.J. et al., 2001].
W omens Health Study, 28 263 ,
- (sP-)
,
. -
- . ARIC [Hwang S.J. et al., 1997]
- , -
. ICAM-1 VCAM-1
, T N F -a, IL-1, IFN-y. ICAM-1
,
, VCAM-1
|:/3
[Blake G.J. et al., 2001].
Physicans Health Study, 14 916 , ,
ICAM-1 (sICAM-1)
(RR 2,8 slCAM-1),
VCAM-1 -
, [Ridker P.M. et al., 1998].
6.11


:
,
FVII,

vWF


: - -, ICAM-1,
VCAM-1; sP- sE-, sICAM-1, sVCAM-1


: TNF-a, IL-1b

, -1-

, PAI-1, -1 ( )

:
TF
, , , ,
N0

8 24

in vitro
, T N F -a VCAM-1
1-1 1L-1 -, ICAM-1, VCAM-1 [Simoncini . et 1., 1999J.
,
, (-, ICAM-1,VCAM-I )
,
[Cushman . et al., 2002].

. PEPI (Postmenopausal Estrogen/Progestin Interventions
Study), ,
, sE- .
, sE-
[Cushman . et al., 1999].
. Koh . (1999),

(, , ).
.
,
,

NF-kB,
.
:
, VCAM-1
. ,

, NF-kB -1. , D. Hamish
. (2000) , , ,
NF-kB HepG2.

-1,
. -1

,
,
[Goodev et al., 2002]. -1
, .
-1
[Koh ., 2002]. -1
.
T N F -a ,

. A. NiemannJonsson . (2000),
T N F -a. T N F -a

6.

825


. TNF-a .
T N F -a
. T N F-a

.
T N F -a , Jun- [Koh .,
2002].
. ,

[Lowe G.D.O. et ., 2005].

.
.
PDGF TGF-p.
,
.
,

. -; ,
- ^ IFN-y
. ,
,
[Braunstein J.B. et ., 2002]. ,

,
.
-1 ,

TF .
[Pradhan A.D. et al., 2002].
-1,
.
.

,
, 1L-6,
IL-1 TN F-a. ,
, IL-8,
- ,
[Lowe G.D.O., 2005].
. Cushman . (1999),
, ,
, ,
-1-,
.
27 -

826

.
, ,
. ,

,
.

. - . Ernst . (1993),
,
, - .
-1- ,
, M RFIT [Kuller L. et al, 1996],
. , -1-
,
. ,
, ,
, 59% [Cushman
. et al., 1999].
.
P.M. Ridker P. (1999) 2
( 51 )
(
).
PEPI (Postm enopausal Estrogen/
Progestin Interventions Study) ,
(, +
, + , +
) [Cushman . et al., 1999].
6 .3 .9 . -

1930 . Tillet Francis.


, -
- Streptococcus pneumoniae.
. ,
0,8 / ,
10 . . 6
,
48 [Hirshfielf G.M . et al., 2003].
,
, .
American Heart Association (2003),
. - 22 -

6.

827

, , ,
2 [Danesh J. et al., 2004].

.
6 ,
, .

(
).
,
,
.


,

[Tracy R.P. et al., 1999]. ,
. MRFIT (Multiple Risk
Factor Intervention Trial)
. P. Ridker
. (1998), ,
WHI, , 6
[Ridker P. et al., 1998]. British Womens
Heart and Health Study [Lawlor D.A. et al., 2005],
.
,
,
.
, ,

.
,
.
IL-lb, IL-6, T N F -a .
FcyRII ,
.
,
(ICAM-1, VCAM-1, -) -1
[Blake G.J. et al., 2001].
, , , .
Clq
, , ,
TF .


- . N 0

828

, ,
, ,
, .

,
[Bruil D.J. et al., 2003].

,
[Blake G.J. et al.,
2001].
, IL-6, IL-1 T N F -a. ,

, . ,
. ,
,
. J. Pankow .
(2001), ,
, . . Margaglione
. (2000) ,
2230% ,
, , , . ,
(+1444 ) ,
,
.
(+1444 >) ,
,
. ,
, ,
3U T R , .
( 2,5 ),
.
, IL -6 IL-lb.
IL-lb +3954 ( 5)
[Gonsalez-Ordonez A. J., 2005].
,
.

IL-6.
, . IL-6
, (,
FVI1I, ), T F vWF.
D. Sukovich . (1998), 2
IL -6
. ,
, 1L-6 .
,

6 .

829

,
,
.


.
,
.
17-

[Stork S. et al., 2002]. . Prestwood . (2004)
,
2 (0,25-0,5 )
. ,
.

: ,
[Sattar N. et al., 1999], .
,
,

. ,

,
.
(,
, ).
WHI ,
, , SAA, IL-6, sICAM,
.
,
.
,

.
-
,
,
( ,
, ).

, ..
,
.
, ,
,
[Kennon S. et al., 2001].

830

(
56%) .
,
( CARE) [Ridker P.M. et al., 1998]. ,
N 0
.
6.3.10.


. P. Kamphuisen . (1999),
, , , .
R. Vormittag (2005)
.

. , ,
VII, vWF, .
.
, , VIII
vWF ,
. , . Sailer . (2005),
,
, ,
.
van . Akenen . (2002), IL-8
(RR = 1,7),
. IL-8 .
,
. ,
, . ,
IL-8
, .
-R.
FV Leiden, , ,
, , VIII. ,
-R.
VIII
.
VIII
IL-lb (+3954 >), IL -6 (-1 7 4 G >C ), -1 (-2518 A>G)
-R -1 [GonsalezOrdonez A.J., 2004].
,
.

.

6.

831

6.3.11 .



, , -

-
.
: , in vitro -1
, in vivo '
.
in vivo, ,
. ,
,
,
,

.

[Stork S. et al., 2004].
,
,
,
.

, , , ,
, , ,
.

.
. ,
.
,
, , .
(T N F -a, IL-1, IL-6),
, ,

. , IL-6
[Woods A. et ., 2000].
,
. ,
. ,
T F -1,
. , ,
-

832

, ,
.

.

. , , I L - 6 , sIC A M -1 [Blake G.J. et
al., 2001].

, . ,
, ,
,
,
, .
,

,
(. 6.2)
70% ,
,
2 ( 6 )
[M ikkola T.S. et
al., 2002].
.

[Hanke ., 1999].
.
, ,
, .
,

.
,


70%
50%

. 6.2.
( M.R. Adams ., 19970)

6.

833


, , , .
, . Daly . (1996),
2 , . (Kannel W.B. et al., 1996), 30 65
20 ..,
10 ..
0,5 .., 2,3 .. ,

.
,
- ,
(H E R S, W H I),
,
1015 .
.
,
.
. M endelsohn . (1999), ,
, .
,
,
(. 6 . 12).
,

. , NAM S, ,
WH1, 2
[Utian W .H., 2004].
,
.
, -

6.12


( H.P.G. Schneider ., 2005)

HERS

67
66
63

0,99
1,29
1,99
1,2

Papworth

1,24

ESPRIT
CAPS
WHI
: ERA,
WAVE, WELL HART

65
63
66

834

() , , , ,

,
.
.

,
, / . ,

,
.



.
6 .3 .1 2 .


.
.
1997 . . Sudhir,
31 - ( / 157 2) (. 6.3).
,
, .
. Lehtimaki . (2002), Pvull (
/ 1/2 1)
, .
, 53 /
,
/ 5 /.
( 6,2 /
10,6 / / ).
,
,
. , V. Ferrero . (2003) , Pvull /

6 . , .

,

.

. , -

6.

835

IVS1 -397 / (Pvull)

. 6.3. -


,

.

. M endelsohn . (2004), 854
873 , 51 .
( / , 454-397 / , 454-397 /,
975 G /G )
, .
D. H errington . (2002)

. IVS1-401 / , 20%
, -,
, /
, / /
. IV S1-401
. -
B -m yb, , ,
.
,
rVS 1-401 /
/ IVS1-401 / [Schuit S.C.E. et al.,
2004].
. B-myb ,
. , IVS1-397 /
-
IVS1-397 / / [Cushm an . et al.,
2004].
7- (
55 ), , Pvull Xbal
, ,
, (R R =2).
[Schuit S.C.E. et al., 2004].
,
.

836

.
, G. Rubanyi . (1997) ,
NO.

, ,
.
, Pvull / Xbal /
,
[Schuit S.C.E. et al., 2004].
IVS1-354 G/
[Cushman . et al., 2004]. IVS 1-345 G /G
12%
2 , TVS 1-354 G/ /
- . ,
, .
. Kunnas . (2000) , -

.
.
,

, .
.
6.3.13.

.
( ),
,
,

(. 6.13).
,
, --
, VII, IX, X, XI, XII, XIII.
,

.

: PC, PS, AT III. ,
. -R
FV Leiden. ,
, -R .
-R
FV Leiden
FV Leiden.

6.

837
6.13

, S, ,
1
1
III

; , , VII, IX, X, XI, XII, XIII,
vWF, TF,
4
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:
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t-PA ( )
t
-

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.. ,

t a r *.
' 11 ; 1 1

...

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* OK III .

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.
, ,
.

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,
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, , , .
, ,
. I ,
, , . .
. - ,
,
.
.
,
(
0,625 1,25 ) [Cano A. et al., 2001].
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X , .

96%

838

III , 3035 ,
, 20 .
OK III -R.
OK III
.
. , OK III
:
, .
OK III OK II
. , OK III
,
FV Leiden, -R.
(,
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OK III
. , ,
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, vWF, , PS.
PAI-1, , .
,
.
.
(2 ) (10 )
() ( 19- )

(
PC, PS, AT III, APC-R),
( F1+2).

.

.
,
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XII
. , XII
6 17-.
, ,
.

TF ,
.
TF
3 , .
, TF
.

6.

839

vWF 2
17- 35 .
t-PA
.
t-PA .
t-PA .
, AT III
(-
),
III.
PAI-1 . , ,
. 17-
1-1, - .
, -1

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. , .
,
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, ,
[Herrington D.M. et al., 2002].
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, .
^
11- 2 ( 2040%).
,

9- .

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1824 .

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( 48 )
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840

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), .
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.
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.
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,
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X
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S

F1+2

t-PA
PAI-1
PAP

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+
+
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+
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+

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,
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?

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vWF.

.
VIII. A.W. Tsai .
(2002), 19 237 7,8 ,
VIII vWF , .
PAI - 1 ,

. Northwick Park Heart Study [Meade T.W. et al.,
1993], PAI-1
. PAI-1
, , .
, F1+2, -,
,
. F1+2
, .
,
. vWF,
.
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,
VII
.
VII
,
. ,
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AT III, PC
PS. PC
PS, -R
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-R . , ,
,
.

.
.
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, -
, .
. Teede . (2000), 6 . (2 1 -

842

) F 1+2, HERS
F 1 + 2
4 . . ,
. ,

.
. Koh . (1997), PAI-1 50%.
1-1 .
4- PAI-1 . ,
4- PAI-1 .
, ,
1-1. , 4 -
.
,

, , .
, .
, -
. Walsh ., Ghjcnj 390
, 8 . ( 0,625 / + 2,5 /)
8% - . , .
,
,
.
,
, .
- P. Scarabin
. (2003) , , ,
-R
( , XI).

PAI-1, t-PA , ,
. ,
,
(. 6.15). ,
17-,
.

.
,
.
, ,
,
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,

fnara 6.

843

6.15

. Daly . (1996)
P. Scarabin . (2003)
S. Perez-Gutthann . (1997)
ESTHER (1998) ( , 155
, 1
)





4,6
3,6
2,1
3,5

2,0
1,0
2,0
0,9

, ,
, ,
.

6.4.

,
, ,
, ,
,
.
: (
, ), (,
, ), (
, , , ).

,
.

,
,
,

.

. ,
70%
OK [Beaumont V. et al., 1992].


. ,

844


,
.
[Nojima J. et al.,
2005].
.
, - Va Vila. ,
,
S .
,
.
.

,

FV Leiden
( , S, III). ,
FV Leiden
2- I
, [ R. et al.,
2004].
, ,

, IgG -|32- I [Vad S. et al., 2003].
,

. , ,
,
IL-6
-2- I, IL-6
[Salobir . et al., 2004].

-. -
.
,
(IL-6, T N F -a, IL-1),
(. 6.4)
,
.

,
.
, .
,
. -

(7

6.

845

IL-6
1

-2-
. 6.4. :
IL-6, -2-1 -.
-2-(1 ,

. ,
[Carlsten . et al., 1992].
IgG IgM [Verthelyi D. et al., 1997]. ,
,
- -.
(
),
. ,

IFN-y, IL-4
[Verthelyi D. et al., 2001].
-
[Grimaldi .., 2006].

. ,
[Kanda N. et al., 1999]. ,
Nurses Health Study (n = 69,435)
,
2,5 [Sanchez-Guerrero J. et al., 1995].
.

351 , ,
,
[Buyon J.P. et al., 2005].

846

.
,
,
( ,
). ,
,
.
.

. ,
,
.
,

,
.

6 .5 .

. ,

.
.

, .
.

.

.

.
, 35
II (150 1 ). OK III
.
.

.

.
- ,
, .
50%
.
( , ) .

6.

847


.
1-2 [Skouby S.O. et al., 2004].
23 .
, .

, ,
.

.

, , WHI, 29%.

.
5 .
.
,

( 40%).
34 .
2 .
,
.

, .
.
,
, , , .

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'/3 -;
HERS 8 ,
, .
, ,
5 .
J. Yates . (2004), 5

, (RR 1,65).
(European Agency for the Evaluation of Medical Products),

. , SERM (
), , D

, .
,
. . Prestwood .
(2003) 17- 0,25 /

848

3 ,
, .

5 /. , ,
, 10 / ,
14 /.
[Santoro N.
et al., 2003].

.
,
.

.
.
NAMS (North American Menopause Society),
65
[Utian W.H., 2004].
,
.

,

.
6.16

,




1.
2.

3. -
4. -
5.

6.
7.
8.

1. .
2. .
3. - : , F1+2,
-, , , .
4. -R, FVIII.
5. :
FV Leiden
PtG20210
MTHFR 677
PAI-1 4G/5G
GPIa
807/, GPIIIa 1565/, GPIba 434
t-PA I/D, I/D.
6. -
: IVS1-401 /, IVS1-397C/T, IVS1-354G/A,
Pvull /, XbalA/G.
7. (- )

6.

849

(
, ), ,
, , , , , 70%

() [ .., 2003].

(, F1+2, -, ).
1 3 . (, -,
).
.



.
,
,
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0,625 + 2,5 62,7 (..
12 ). WHI ,
.
,
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?
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:
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;
,
;
,
;

.


. 0,625 , 12 17- 50 .
. 6.17.

850

6.17

,


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17/3-,

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0,3
0,5-1
0,5-1
25

0,625

1,25

1-2
1-2
50

4
100


0,3 , 0,5 ,
0,25 0,014
[Ettinger . et !., 2004].
. Peeyananjarassri . (2005)

.
3 .
. ,

, .. ,

-
(, , - ) .

,
.

,
.
,
, ,
[Peeyananjarassri .
et al., 2005].
, . S. Stork
. (2002)
(ICAM-1, VCAM-1,
-).
. ,

, , .

,
- ,
.

6.

851

,
( 0,3
2,1; 0,625 3,3; 1,25 6,9) [Jick . et al,
1996].
,

,
.
14
26,2%,
0,52,9%, ,
, .

. , 4
2,6%,
39% [Ettinger . et al., 1999].
4 8,3%,
3,8%,
44%, 36% [Cummings S.R. et
al., 1998].
.
,

,
. ,
,
,
.
, ,
. ,
3
845,4%, 0,377%;
0,4% 0%.

0,55% 0,40,8%;
00,8% 0% [Peeyananjarassri . et al., 2005].

- ,
, *
. ,
. .

3 .
:
10
0,76, ( 1020 -

852

1,2, 20 1,22. 23
, 39 049
,
60 (OR = 0.61; 0.39-0.98),

(O R = 1.47; 1.22-1.99), 2
(OR = 0.79; 0.670.93), , 60
(O R = 1.03) [Salpeter S., 2005].
, 50 59 , 0,625
44% , [Ander
son G.L. et al., 2004], ,
- .
:
70% , 2
( 6
) [Clarkson .. et al., 2001].
, -
. , , ..
,
,
KEEPS: The Kronos Early Estrogen Prevention Study [H arm an S. et al.,
2005]:
, , , -

.
: 20052010 .
= 720.
: 4258 , 636 .
:
0,45 / () +
200 () 12

0,05 / () +
+ ,

.
: :
.
, 0,625
.
Nurses Health Study, 0,3
0,625 [Alkjaersig N . et al.,
1988]. 0,3
40% .
0,45 . ,
, .

6.

853

,
, .. ,
, ,
.

,
,
, .



. ,

.
,
, .

.
,
, , , ,
, ,
. ,

.
.
,
, ,

.
,
(, ,
).

.


,
.

.
,

( ,
),
.
, .

854

. .
, : .... -
. . ., 2003. 268 .
Adams M.R., Register .., Golden D.L., Wagner J.D., Williams J.K. Medroxy
progesterone acetate antagonizes inhibitory effects o f conjugated equine estrogens on
coronary artery atherosclerosis / / Arterioscler. Thromb. Vase. Biol. 1997; 17(1):
217-21.
Alexandersen P., Haarbo J., Sandholdt I., Shalmi ., Lawaetz H., Christiansen C.
Norethindrone acetate enhances the antiatherogenic effect o f 17beta-estradiol: a sec
ondary prevention study of aortic atherosclerosis in ovariectomized cholesterol-fed
rabbits//Arterioscler. Thromb. Vase. Biol. 1998; 18(6): 9027.
Alkjaersig N., Fletcher A.P., de Ziegler D., Steingold K.A., Meldrum D.R., Judd H.L.
Blood coagulation in postmenopausal women given estrogen treatm ent: comparison of
transdermal and oral administration / / J. Lab. Clin. Med. 1988 Feb; 111(2):2248.
Anderson G.L., Limacher ., Assaf A.R. et al. Womens Health Initiative Steering
Committee. Effects of conjugated equine estrogen in postmenopausal women with hys
terectomy: the Womens Health Initiative randomized controlled trial / / J.A.M.A.
2004 Apr 14;291(14):170112.
Bauersachs R., Lindhoff-Last E., Ehrly A.M., Kuhl H. Significance o f hereditary
thrombophilia for risk of thrombosis with oral contraceptives / / Zentralbl. Gynakol.
1996; 118(5): 262-70.
Beaumont V, Malinow M.R., Sexton G., Wilson D., Lemort N ., Upson B., Beau
mont J.L. Hyperhomocyst(e)inemia, anti-estrogen antibodies and other risk factors
for thrombosis in women on oral contraceptives / / Atherosclerosis. 1992 Jun;94
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Beral V., Banks Reeves G. Evidence from randomised trials on the long-term effects
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Blake G.J., Ridker P.M. Novel Clinical Markers o f Vascular Wall Inflammation / /
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