1. Hemostasis comprises of
    vascular wall injury, platelet aggregation, coagulation cascade
  2. role of chemicals in vascular injury for hemostasis
    • endothelin-1: Transient vasoconstriction
    • thromboxane a2: platelet agggregation, vasoconstriction
  3. anti thrombogenic are
    • nitric oxide
    • tissue plasminogen activator : fibrinolysis
    • i thrombomodulin: cleaves F Va and F VIIIa
    • prostacyclin (pg i2): anti-platelet aggregation, vasodilation
  4. TXA2 is secreted by
    • Endothelial cells
    • Platelets
  5. Release of tissue factor from injured cells triggers
    • TXA2 release
    • Activation of Factor VII (extrinsic pathway)
  6. Sub endothelial collagen exposure from vessels triggers
    • Activation of Factor XII 
    • in presence of pekallikrein to kallikrein conversion 
    • with HMWK
  7. vWF binds to
    • exposed sub endothelial collage type IV
    • platelet adhesion to vWF via GpIb
  8. Quantitative platelet disordres
    • decreased production: aplastic anemia, tumor
    • increased destruction: ITP, TTP, DIC, Hypersplenism
  9. 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
  10. 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
  11. 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
  12. Forms of ITP
    • Acute: follows viral infection in CHILDREN; self-limiting
    • Chronic: WOMEN of child-bearing years
    • maybe first manifestation of SLE
    • requires treatment
  13. Labs of ITP
    • Prolonged BT
    • Decreased platelet count
    • Normal PT/PTT
    • PBS: immature giant platelets (megathrombocytes)
    • BMA: immature forms, increased megakaryocytes
  14. 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
  15. 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)
  16. 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
  17. TTP lab
    • Prolonged BT
    • Decresed platelet
    • Normal PT/PTT
    • PBS: thrombocytopenia, schistocytes, reticulocytosis (d/t destrn of RBCs)
  18. Schistocytes aka
    Helmet cells
  19. 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
  20. Coagulation Cascade
    • Clotting factors almost exclusively produced by liver.
    • require activation
    • some conversions occur on phospholipid surface
    • some conversions require calcium
  21. 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
  22. Coagulation cascade disorders
    • Hemophilia A
    • Hemophilia B
    • Hemophilia C
    • Acquired coagulopathies: Vit K defeciencies, Liver disease
    • vWB Disease
    • DIC
  23. 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
  24. 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.
  25. Liver disease
    decreased synthesis of virtually all clotting factors
  26. 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
    • Lab: Normal platelet count, Increased BT
    • Normal PT, Prolonged PTT (vWF binds with F VIII- intrinsic pathway)
  27. 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)
  28. 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
  29. Treatment of DIC
    Treatment of underlying cause
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