HEMOSTASIS

 
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–  Second  PHYSIOLOGY  
level  
•  Third  level  
–  Fourth  level  
»  Fi8h  level  

FIFTEEN  APRILA  FAJRIN  

BAGIAN  FKK-­‐FFUJ  
 Outlines…

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–  Second  level   ①  Definition  
•  Third  level   ②  Normal  hemostasis  
–  Fourth  level  
③  Functions  of  vessel  wall,  
»  Fi8h  level  
platelets  and  coagulation  
factors  in  bleeding  
④  Coagulation  and  Fibrinolysis  
 Definition?

Click  tfrom  
• þ Drives   o  edit   Mreek  
the  G aster  text  styles  
–  Second  
-  Heme   :  Bllood  
evel  
-  Stasis   :  to  
•  Third   halt  
level  
þ Hemostasis   à  “lThe  
–  Fourth   evel  
stoppage  of  » bFi8h  
lood  level  
flow”  
þ Repairs  injury  to  blood  
vessels  
þ Stops  or  prevents  blood  
loss  
 Hemostasis???

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à  Hemostasis  is  a  balancing  act  
à Balance  of  bleeding  (hemorrhaging)  and  clotting  (thrombosis)  
–  Second  level  
à  Imbalance  in  one  direction  can  lead  to  :  
•  Third  
–  Bleeding   level  
:  hypocoagulable  
–  Fourth  
–  Thrombosis   level  
:  hypercoagulable  
»  Fi8h  level  
 Hemostasis???

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–  Second  level  
•  Third  level  
–  Fourth  level  
»  Fi8h  level  
 Hemostasis Component

Coagulation  
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System  
–  Second  level   •  Forms  a  stable  
insoluble  plug  
• Platelet  
Third  Slevel  
ystem   (i.e)  fibrin   Fibrinolytic  
•  Interaction  of   forming  
–  Fourth  
vascular   and   level   System  
platelets  
» fFi8h  
orm  al  evel   •  Fibrin  lysing  
temporary  plug  

Coagulation  
Vascular  System   Inhibition  System  
•  Controls  rate  of  
HEMOSTASIS •  Natural  inhibitors  
blood  flow   COMPONENT •  Control  fibrin  
formation  and  fibrin  
lysis  
 NORMAL HEMOSTASIS
-  It  is  a  complex  process  depending  on  interaction  between  
Click  wto  
•  vessel   epdit  
all,   Master  
latelets   text  styles  
and  coagulation   factors.  
  –  Second  level  
BV  Injury  
•  Third  level  
Neural   Tissue  Factor  
–  Fourth  level  
»  Fi8h  level  

Blood  Vessel     Platelet   Coagulation  

Constriction   Activation   Activation  
Primary  hemostatic  plug  
Reduced   Plt-­‐Fusion   Thrombin,  
blood  flow   Fibrin  

Stable    Hemostatic  Plug  

 NORMAL HEMOSTASIS STAGES

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–  Second  level  
•  Third  level  
–  Fourth  level  
»  Fi8h  level  
 NORMAL HEMOSTASIS
Primary  
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and  vascular  
response  to  vessel  injury  
–  Second  level   1.  Together,  platelets,  
vessels,  and  
•  Third  level  
coagulation  factors  à  
–  Fourth  level   combine  to  stop  
»  Fi8h  level   bleeding  
2.  Allow  for  vessel  repair  
through  formation  of  a  
stable  fibrin-­‐platelet  
Secondary   plug  at  the  site  of  
injury.  
àthe  coagulation  factors  
response  to  such  injury  
 NORMAL HEMOSTASIS

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–  Second  level  
•  Third  level  
–  Fourth  level  
»  Fi8h  level  
 Vessel Wall-Endhotelium Action?  

Intact  endothelial  cells    

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–  maintain   e dit  
liquid   M
blood   flaster  
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actively  inhibiting  platelet  
–  Second  level  
adherence  
–  preventing  coagulation  factor  
•  Third  level  
activation  
–  lysing  blood  clot  that  may  form  
–  Fourth  level  
Endothelial  cells  can  be  stimulated  
by     »  Fi8h  level  
–  direct  injury  
–  by  various  cytokines  that  are  
produced  during  inflammation.  
Stimulation  à  expression  of   In  a  normal  individual,  
procoagulant  proteins  e.g.  tissue   coagulation  is  initiated  within  
factor  and  vWf   20  seconds  after  an  injury  
-  contribute  to  platelet   occurs  to  the  blood  vessel  
aggregation  and  local  thrombus   damaging  the  endothelial  cells.    
formation  
 Vessel Wall-Endhotelium Action?  

à FIRST  RESPONSE  
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• à Goal:  
Second  bllood  
• – Minimizes   evel  
flow  
Third  
to  i• njured   level  
area  
–  Fourth  level  
•  Prevents  blood  loss  
»  Fi8h  level  
•  Delivers  platelets  and  
plasma  proteins  to  
the  vessel  wall  
•  Immediate  and  short-­‐
lived  
 Primary Hemostasis?

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After  injury  platelets  
–  Second  level   come  in  contact  with  
•  Third  level   collagen  and  vWF  
–  Fourth  level  
and  undergo  three  
»  Fi8h  level  
changes  
–  Adhesion  and  shape  
change  
–  Secretion  or  release  
reaction  
–  aggregation  
 Primary Hemostasis-Role of Platelets ?  

¤  glycoproteins  Ia  (GP-­‐Ia)  

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collagen  and  (GP-­‐Ib)  which  
–  Second  level   binds  to  Von-­‐Willebrand  
•  Third  level   factor  (vWF)  in  plasma  
–  Fourth  level   ¤  vWF  in  turn  adheres  to  
collagen  à  following  
»  Fi8h  level  
adhesion  à  shape  change  
from  disc  to  sphere  
¤  release  of  content  of  
platelets  granules  (platelet  
release):  ADP  &  serotonin  
and  TXA2,  Platelet  derived  
growth  factor,  Platelet  
factor  4  
 Primary Hemostasis-Role of Platelets ?  

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–  Second  level  
•  Third  level  
–  Fourth  level  
»  Fi8h  level  

à ADP  leads  binding  of  fibrinogen  to  platelet  à  platelet  aggregation  à  forming  plug  
at  site  of  injury.    
à Also  of  normal  platelet  function  is  platelet  prostaglandin  synthesis  which  is  induced  
by  platelet  activation  and  leads  to  formation  of  TXA2à  powerful  vasoconstrictor    
 Primary Hemostasis-Role of Platelets ?  
¤  As  a  result  of  platelet  aggregation;  
platelet  factor-­‐3  is  released  which  
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intiates  blood  coagulation  ground  
–  Second  level   platelets  ,  thrombin  encourage  fusion  
of  platelet  and  fibrin  formation  
•  Third  level   reinforce    stability  platelet  plug  
–  Fourth  level   ¤  Contraction  of  protein  thrombosthenin  
»  Fi8h  level   which  together  with  fibrin  around  form  
hemostatic  plug.  
¤  Prostacyclin  (PGI2)  is  synthesized  in  
vascular  endothelium  and  oppose  the  
action  of  TXA2à  increase  level  of  cyclic  
AMPà  preventing  platelet  aggregation  
on  normal  vessel  wall  as  well  as  limiting  
the  extent  of  platelet  plug  after  injury.  
 Secondary Hemostasis-Coagulation Cascade?

The  coagulation  
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hemostasis  has  two  
–  Second  level  
pathways:  
• CThird  
þ  the   ontact   level  
Activation  pathway  
–  Fourth  level  
(formerly  known  as  
the  Intrinsic  »  Fi8h  level  
Pathway)    
þ  And  the  Tissue  Factor  
pathway  (formerly  
known  as  the  
Extrinsic  pathway)  
that  lead  to  fibrin  
formation.  
 Coagulation Cascade-Coagulation Factors

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 =  Fibrinogen  
–  Second  Factor  
level  II    =  Prothrombin  
Factor  III    =  Tissue  thromboplastin  
•  Third  level  
Factor  IV    =  Ionisable  calcium    
–  Fourth  level  
Factor  V    =  Proaccelerin  or  labile  factor  
»  Fi8h  level  
Facto  VII    =  Proconvertin  or  stable  factor  
Factor  VIII  =    Antihemophilic  factor  (hemophilia      A)  .  
Factor  IX    =  Christmas  factor  (hemophilia  B)  
Factor  X    =  Stuart  –  Power  factor    
Factor  XI    =  Plasma  thromboplastin  antecedent  
Factor  XII    =  Hageman  factor  
Factor  XIII  =  Fibrin  Stablizing  factor.  
 
 Coagulation Cascade-Coagulation Factors

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–  Second  level  
•  Third  level  
–  Fourth  level  
»  Fi8h  level  
 Secondary Hemostasis-Coagulation Cascade?

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–  Second  level  
•  Third  level  
–  Fourth  level  
»  Fi8h  level  
 FIBRINOLYSIS
-  Fibrinolytic  system  is  involved  
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in  fibrinolysis,  tissue  repair  
and  vessel  rebirth.  
–  Second  level  
-  It  helps  to  restore  vessel  
•  Third  
potency   level  of  
by  dissolution  
fibrin.   –  Fourth  level  
-  Normal  plasma  p Fi8h  level  
» rotein  
Plasminogen  (formed  in  the  
liver)  is  converted  by   Blood coagulation and fibrinolysis
Plasminogen  activators  
derived  from  plasma  
endothelial  cells,  platelets,  
leukocytes  and  urine  into  
plasmin  
 FIBRINOLYSIS
Activation  by:  Plasminogen  
activator  (extrinsic),  intrinsic,  
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exogenous.  
– of  Second  
2  types   level  
Plasminogen  
activator:  
•  Third  level  
•  Tissue  Plasminogen  
Fourth  
activator  f– ormed   in  tlhe  
evel  
vascular  endothelium  
»  Fi8h  (lt-­‐PA).  
evel  
•  Tissue  Plasminogen  
activator  formed  in  the  
kidney  (Urokinase/u-­‐PA).  
•  t-­‐PA  is  inactivated    by  
Plasminogen  activator  
inhibitor  I.    
Intrinsic  à  factor  XIIa,  HMWK,  
Kallikrein  
Exogenous  à  Streptokinase  
(a). Process of
hemostasis
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–  Second  level  
(b). The•  Third  level  
synthesis – ofFourth  level  
fibrin in blood »  Fi8h  level  

clots
 Secondary Hemostasis-Anti Coagulant?

Intrinsic Extrinsic

thrombin
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–  Second  
XI
level  
XIa
•  Third   level   TF
IX IXa VIIa VII
–  Fourth  level  
VIII VIIIa
»  Fi8h  level  
X ATIII
protein
C
V Va Xa

prothrombin thrombin

fibrinogen fibrin clot

 THROMBOSIS

à  Hemostasis  is  normally  beneficial  BUT  if  inappropriately  

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activated  can  be  harmful  
–  Second  level  
à  Distinguish  
•  Third  lbevel  
etween  these  words  
à  Thrombosis   (pathological)  
–  Fourth   level   :  A  solid  mass  of  blood  constituents  
[thrombus]   formed  
»  Fi8h   within  the  a  vascular  lumen  during  life  
level  
à  Clot  :  A  solid  mass  of  blood  constituents  occurring  outside  the  
vascular  tree  OR  after  death  within  the  vascular  tree  
angan

ekuan
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–  Second  level  
uan/ •  Third  level  
kit –  Fourth  level  
»  Fi8h  level  
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–  Second  level  
•  Third  level  

Thank You –  Fourth  level  

»  Fi8h  level