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1.0 Platelets, Blood Coagulation and Fibrinolysis Disorders Fresh frozen Plasma
Dr. Espiritu/ February 21 3. ANTIPHOSPHOLIPID ANTIBODY SYNDROME (APAS)
Laboratory PRELIMS -can occur as a primary syndrome called APAS or secondary
Red: Emphasized; Blue- Audio; Green- OT syndrome like in SLE there is the formation of antiphospholipid
antibodies (anticardiolipin)
-high titers of circulating antibodies against anionic
DISSEMINATED INTRAVASCULAR COAGULOPATHY
phospholipids (e.g. cardiolipin)
2 pathological processes taking place simultaneously:
- Clue to diagnosis: false positive syphilis test because the reagent
activation of fibrinolytic system
uses cardiolipin
Consumption of Coagulation Factors
** phospholipid surface- where the formation of blood clot takes
place
Formation of multiple thrombi leading to
**Coagulation cascade will need a phospholipid surface for it to
consumption of coagulation factors.
function optimally
Settings associated with DIC development:
In vitro: antibodies interfere with coagulation assays
DIC is a secondary disorder, there will always be an inciting factor
that make use of phospholipid reagents or are phospholipid
dependent (ex. aPTT). Therefore, coagulation tests are manifested
o sepsis (mostly gram negative bacteria, some gram positive
with prolonged results; multiple thrombi in any
and viruses) o endotoxins; but gram positive bacteria has
organ system
endotoxin-like property
o Trauma and tissue destruction
in vivo: induce a hypercoagulable state
o Malignancy (lung Ca, Leukemia)
*** Main manifestation of patients with APAS would be multiple
o Obstetric complication
thrombi formation occurring in many organ systems
(hypercoagulable)
Complications:
** The effects of antibody in vivo interfering in the coagulation
shock
**patient with repeated abortion work up for APAS possible
hemorrhage preceded with wide spread thrombosis
pregnancy
renal failure
ORGAN SYSTEMS INVOLVED:
LABORATORY DX:
- peripheral venous system
- CNS
Fibrinogen Decreased one of the most
- hematologic
important factor in
- obstetric, pulmonary
the coagulation
- dermatologic
cascade
- cardiac
consumption
- ocular
coagulopathy
- adrenal
PT Prolonged consumptive
- musculoskeletal
coagulopathy- all
factors are
Laboratory characteristics:
involved all
Hematologic establishment of APAS:
factors are
decreased
1.Prolonged aPTT, Russel Viper Venom time, or Kaolin clotting
aPTT Prolonged Prolonged time
Platelet count Decreased first step in Russel Viper Venom time
coagulation is the -reagent (venom) - could induce thrombosis
formation of -If patient has antiphospholipid antibody or anticardiolipin this
primary plug would interfere with thrombosis, thus RVVT is prolonged)
Fibrin split Increased Activation of
Kaolin Clotting time
products fibrinolytic system
-provide a glass particle as an additional surface for contact
-destruction of
inhibition
fibrin
*modification of aPTT
Protamine sulphate test Increased Sensitive test for
***aPTT, Russel Biper venom Time, Kaolin Clotting time
Fibrin monomers and DIC: detects fibrin
PROLONGED
early fibrin products monomers and
early fibrin
2. Failure to correct the test by mixing patient plasma with
degradation
normal plasma (suggesting a clotting inhibitor is present)
products (same
-Suggest a mixing study, get the plasma from a normal person the
principle
mix it with the patients plasma--- determine aPTT
with fibrin split
-Coagulation deficiency: normalize (due to addition of deficient
products BUT
factor)
becomes
-APAS: it will not normalize
positive earlier)
3. Normalization of the test with freeze-thawed platelets (contain
Treatment:
phospholipids) or phospholipids
Heparin
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-Test will normalize due to addition of naturally occurring
phospholipid which is needed PLATELET DISORDERS
*** Immunologic establishment of APAS:
4. Specific assay for anticardiolipin A.Autoimmune thrombocytopenias
1. Immune thrombocytopenic purpura(ITP)
HYPERCOAGULABLE STATE (THROMBOPHILIA) It is one of the most common autoimmune disorders. It occurs in
-Deficiency in naturally occurring anticoagulants (Factor C and S) 2 distinct clinical types:
-Factor C is Vit k dependent ACUTE
-rare - self-limiting form observed almost exclusively in children (5
cases per 100,000 persons)
Leiden mutation (FACTOR V) -usually preceeded by viral infection
-Factor V cannot be inactivated by Protein C due to the mutation -BM shows normal or an increase in megakaryocyte
-5-10 yrs., can go to chronic
PLATELET PHYSIOLOGY
-The hemostatic system consists of platelets, coagulation factors, CHRONIC form,
and the endothelial cells lining the blood vessels. -observed mostly in adults (3-5 cases per 100,000 persons) and
-platelets arise from the fragmentation of the rarely in children
cytoplasm megakaryocytes in the bone marrow and circulate in -more common in FEMALES
blood as disc-shaped anucleate particles. -Insidious onset
-last for years
Thrombopoietin:
-regulation of Platelet production produce by liver and kidney Manifestations:
- -Skin pupura
-_______ the number 1 rate of maturation of megakaryocyte -Superficial bruising
-Epistaxis
Platelet Count: 150-450/cumm -Menorhagia
Normal Lifespan: 7-10 days -Massive haemorrhage is seen in severe cases
About 1/3 are trapped in the spleen -infection
-Splenomegally in 10% of Cases
Function:
-Formation of mechanical plud during nrmal hemostatic Laboratory Findings:
response to vascular injury -Thrombocytopenia with giant forms
-the main steps are: Adhension, release and aggregation -Platelet Count usually 10-50,000
-BM shows normal and increase megakaryocyte
Platelet Adhesion-adhesion to subendothelial collagen -Platelet bound IgG is (+)
-dependent of VW factor
Pathogenesis:
Release (Secretion) ITP is caused by autoantibodies to platelets. The
-Collagen exposure result in the release of granular contents antigenic target in most patients appears to be the platelet GP
(ADP, Serotonin, Fibrinolysis) IIb/IIIa complex. Platelets with antibodies on thei surface are
-Collagen and thrombin activates PG synthesis trapped in the spleen, where they are efficiently removed by
splenic macrophages. The mechanism of origin of these
Memb platelet antibodies is not known. These antibodies may be directed
toward the viral antigens and then cross-react with platelet
Arachidonic Acid(cyclooxygenase Pathway) antigens. They persist because of the failure of immune
surveillance mechanisms to repress these antibodies. These
Thromboxane Synthesis antibodies can also react with the developing megakaryocytes in
the bone marrow, leading to decreased protection of platelets
Thromboxane A2 (ineffective thrombopoiesis). The success of thrombopoietin
(potential aggregration) agonist in chronic ITP underscores this mechanism as a major
factor in inducing thrombocytopenia.
Platelet disorders: ITP occurs commonly in otherwise healthy individuals and only
-most common cause of bleeding rarely as the initial manifestation of lupus and other autoimmune
-the disorder could be due to number of defective function disorders. Human immunodeficiency virus (HIV) infection is
often associated with immune thrombocytopenia in both adults
Thrombocyptopenia and children.
-decrease platelet in the circulation
- ____ of Platelet from the circulation is faster than the rate of their Other Causes:
production by the bone marrow -BM Supression
-failure of platelet production -DIC
-Drugs due to suppression e.g., phenylbutamine, gold, thiazide
Causes of thrombocytopenia
CONGENITAL: megakaryocyte hyperplasia, micolt Infections:
aldric -decrease platelets can be seen in many infections
ACQUIRED: Acquired, Immunothrombocytopenia, DIC< -effects is due to suppression of the bone marrow, immune
Drugs, Infection, Splenomegally, Aplastic Anemia medications or due to DIC in fulminant infections

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Defective Platelet Function
-a defect in function is suspected if there is chronic Blood
transfusion with or without skin or mucosal hemmorhage in the
___ of normal patients

Disorders of the Paltelet Function

-Congestion
-Gleamman Disease

Acquired Disorders of the Plalete Fucntion

-Causes:
Drugs-e.g., Aspirin
Myleproliferation disorders
Autoiimune disorders

DRUGS:
-best example is Aspirin which is the most common cause of
acquired paletlet frunction
-aspirin irreversibly affected the cyclooxygenase enzyme

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