1. GP1b-V-IX
    a platelet cell-surface receptor that binds to vWF; involved in adhesion of the platelet to the epithelial surface
  2. GPIIb3a
    a platelet cell-surface receptor that binds fibrinogen to cross-link platelets
  3. platelet activators
    activate platelets via binding to cell surface receptors; include collagen; thrombin; TXAA2; ADP
  4. platelet activation
    involves formation of pseudopods that increase cell membrane surface area; involves extrusion of alpha and dense granules (containing ADP and 5-HT and other proteins that provide positive feedback); results in exposure of membrane phosphatidylserine (which is usually found on the cytoplasmic side of the cell) - provides a surface for coagulation; ultimately results in platelet aggregation
  5. von Willebrand factor
    vWf; acts as an intermediate in adhesion of platelets to the cell surface; also serves as a carrier for factor VIII
  6. fibrin vs. fibrinogen
    fibrinogen is a soluble plasma glycoprotein synthesized in the liver that is symmetrical and can bind GPIIb3a at both ends; fibrin is an insoluble fibrous protein that forms the meshwork for a blood clot; fibrinogen is converted to fibrin via limited proteolytic cleavage by thrombin; fibrin formation results in release of fibrinopeptides A and B
  7. factor VIII
    Factor VIII is a clotting factor involved in the cross-linking of fibrin molecules; is activated to factor VIIIa by thrombin; uses vWf as a carrier protein
  8. thrombin
    a serine protease; produced from prothrombin in a vitamin K-dependent process that utilizes factor X as a cofactor; cleaves and activates many clotting factors; activates the anticoagulant factor protein C; converts fibrinoget to fibrin by cleaving fibropeptides A and B from the E domain of fibrinogen - this allows the D and E domains to bind
  9. extrinsic pathway of the coagulation cascade
    occurs outside of blood vessels due to exposure to subepithelial components; requires calcium; involves activation of factor VII to factor VIIa using factor Xa; factor VIIa then activates factor X to Xa using Tissue Factor as a cofactor; factor Xa activates prothrombin to thrombin; 'chicken and egg' situation w.r.t. factors VIIa and Xa
  10. intrinsic pathway of the coagulation cascade
    occurs inside the vascular system; contact activation on a negatively charged surface activates factor XII to XIIa via the enzyme Kallikrein; factor XIIa converts factor XI to XIa; factor XIa converts factor IX to IXa; factor IXa forms a complex with Ca2+ & factor VIIIa & phospholipid to cleave factor X to Xa; factor Xa cleaves prothrombin to thrombin; thrombin feeds back to cleave more factor V & VIII & XI
  11. interactions between the extrinsic and intrinsic pathways
    both pathways converge on the activation of factor X to Xa; the extrinsic pathway can stimulate the intrinsic pathway directly via a crossover step; this involves the cleavage of factor IX to IXa by the factor VIIa-Tissue Factor-calcium complex
  12. prothrombinase complex
    formed by factor Xa and factor Va and Tissue Factor and calcium; cleaves prothrombin to thrombin; reaction takes place on the platelet surface and releases thrombin upon activation
  13. vitamin K-dependent reactions
    involve serine proteases with a Gla domain that inserts into the platelet membrane; serine proteases with a Gla domain require post-translational modification by vitamin K to bind calcium; calcium allows the Gla domain to bridge negatively charged interactions with the cell membrane; substrates include prothrombin & factor IX & factor X
  14. mechanism of warfarin action
    Warfarin inhibits the enzyme that converts inactivated vitamin K to its active reduced form; this inhibits vitamin K-dependent reactions
  15. mechanisms for termination of the hemostatic process
    1. binding & inactivation of thrombin & factor VIIa & Xa &IXa by antithrombin III (a serpin - suicide protein); 2. inactivation of factor Va and factor VIIIa by activated protein C; 3. inactivation of factor VIIa & factor Xa by tissue factor pathway inhibitor (TFPI)
  16. mechanism of heparin action
    accelerates inactivation of hemostatic process by binding to antithrombin & protease - brings them closer together; induces conformational changes in antithrombin that allows it to bind more effectively with factor Xa
  17. fibrinolysis
    involves cleavage of fibrin between D and E domains by the serine protease plasmin; plasmin is the activated form of plasminogen; t-PA & u-PA (endogenous) & streptokinase (produced by bacteria) both activate plasminogen to plasmin
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