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Hemostasis comprises of
vascular wall injury, platelet aggregation, coagulation cascade
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role of chemicals in vascular injury for hemostasis
- endothelin-1: Transient vasoconstriction
- thromboxane a2: platelet agggregation, vasoconstriction
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anti thrombogenic are
- nitric oxide
- tissue plasminogen activator : fibrinolysis
- i thrombomodulin: cleaves F Va and F VIIIa
- prostacyclin (pg i2): anti-platelet aggregation, vasodilation
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TXA2 is secreted by
- Endothelial cells
- Platelets
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Release of tissue factor from injured cells triggers
- TXA2 release
- Activation of Factor VII (extrinsic pathway)
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Sub endothelial collagen exposure from vessels triggers
- Activation of Factor XII
- in presence of pekallikrein to kallikrein conversion
- with HMWK
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vWF binds to
- exposed sub endothelial collage type IV
- platelet adhesion to vWF via GpIb
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Quantitative platelet disordres
- decreased production: aplastic anemia, tumor
- increased destruction: ITP, TTP, DIC, Hypersplenism
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thrombasthenia:Qualitative platelet disorders
- vWB disease: qualitative deficiency of vWF
- Bernard- Soulier Syndrome: defeciency of GpIb
- Glanzmann thrombasthenia: inactive Gp IIb-IIIa complex
- Drugs: aspirin
- Uremia: inability of kidney to get rid of waste products
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Function of platelet surface glycoproteins
- Gp Ib: adheres platelet to vWF
- Gp IIb-IIIa complex: undergoes confirmational change to allow fibrinogen to strengthen adhesion between adjascent platelets
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ITP
- hypersensitivity rxn type ii
- antiplatelet antibodies against platelet antigens Gp IIb-IIIa, Gp Ib-IX
- antibodies made in spleen
- platelet destroyed peripherally in spleen by macrophages
- macrophages contaion Fc receptors that bind igG coated platelets
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Forms of ITP
- Acute: follows viral infection in CHILDREN; self-limiting
- Chronic: WOMEN of child-bearing years
- maybe first manifestation of SLE
- requires treatment
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Labs of ITP
- Prolonged BT
- Decreased platelet count
- Normal PT/PTT
- PBS: immature giant platelets (megathrombocytes)
- BMA: immature forms, increased megakaryocytes
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ITP therapy
- corticosteroids: decrease ab production
- immunoglobulin: floods Fc receptors on splenic macrophages so no platelet bind to them
- Splenectomy: remove site of ab production and platelet destruction
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TTP
- Defeciency/ Inhibition of ADAMTS-13
- ADAMTS-13 : responsible for cleaving large multimers of vWF within endothelial cells (-)
- Hence, widespread intravascular formation of fibrin-platelet thrombi
- Pathology: Form of thrombotic microangiopathy (intravascular hemolysis d/t hyaline thrombi formed byplatelet within fibrin)
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TTP features
- adult women
- PENTAD:
- Fever: reduced distal capillary perfusion d/t thrombi--- capillary injury--- TNF-1 released
- Thrombocytopenia: platelet consumption
- Microangiopathic hemolytic anemia: RBCs squeeze thrombi and get severed thus schistiocytes in PBS
- Renal features: uremia
- CNS features: confusion, coma
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TTP lab
- Prolonged BT
- Decresed platelet
- Normal PT/PTT
- PBS: thrombocytopenia, schistocytes, reticulocytosis (d/t destrn of RBCs)
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Schistocytes aka
Helmet cells
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HUS
- Form of thrombotic microangiopathy d/t endothelial cell damage, predominantly in kidney but not invariably
- common in children
- Follows gastroenteritis with bloody diarrhoea
- Cause: organism, verotoxin producing E.coli O157:H7
- Triad: Thrombocytopenia, Microangiopathic hemolytic anemia, Renal (features of uremia)
- Pentad of TTP maybe present
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Coagulation Cascade
- Clotting factors almost exclusively produced by liver.
- require activation
- some conversions occur on phospholipid surface
- some conversions require calcium
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Lab parameters for cascade involvement
- PT : shows involvement of extrinsic pathway, normal range- 10-15secs, >15 secs is prolonged
- PTT : shows involvement of intrinsic pathway, normal range- 25-35 secs, >35 secs is prolonged
- Thrombin time : time required for conversion of fibrinogen to fibrin, shows adequate fibrin levels
- FDP/FSP/D-dimers: byproducts of fibrinolysis, test fibrinolytic system, increase in DIC
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Coagulation cascade disorders
- Hemophilia A
- Hemophilia B
- Hemophilia C
- Acquired coagulopathies: Vit K defeciencies, Liver disease
- vWB Disease
- DIC
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Hemophilia
- XLR, predominantly in males
- Lab: Normal plateletcount, Normal BT, Normal PT
- Prolonged PTT due to involvement of Factor VIII
- Factor VIII(A) / IX(B) defeciency
- Hemophilia C: FXI defeciency, AR
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Vitamin K defeciencies
- Involvement of factors ii (CP), vii (EP), ix (IP), x (CP), proteins C, S
- Lab: both APTT and PT increase (extrinsic, intrinsic and combined pathway involved) but t1/2 of F VII is short, so PT is first to prolong.
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Liver disease
decreased synthesis of virtually all clotting factors
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vWB Disease
- inherited bleeing disorder
- defeciency or qualitative defect in vWF
- normally produced by endothelial cells and megakaryocytes
- c/f: spontaneous bleeding from mucous membraned
- bleeding into joints is UNCOMMON
- Normal PT, Prolonged PTT (vWF binds with F VIII- intrinsic pathway)
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DIC
- always secondary to another disorder
- Causes:
- Obstetric complications: placental TISSUE FACTOR
- Gram Negative Sepsis: TNF activates clotting
- Microorganisms: Meningococcus, Septicemia
- Leukemia: AML M3 (cytoplasmic granules- Auer rods activate clotting)
- Adenocarcinoma: pancreas, breast,etc (mucin activates extrinsic pathway, can substitute for TF)
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Lab for DIC
- Decreased platelet: consumed
- Prolonged PT/PTT: clotting factors all consumed
- Decreased fibrinogen
- Increased D-dimer: fibrinolytic system activated to lye the disseminated thrombi
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Treatment of DIC
Treatment of underlying cause
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