Hemostasis

  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
Author
Binita
ID
340601
Card Set
Hemostasis
Description
Revision of mechanism of hemostasis and associated disorders
Updated