PHA3801 Lecture Notes - Lecture 1: Glycosaminoglycan, Halothane, Hyperthyroidism
24 Jul 2018
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Clot formation: damage endothelium reveals underlying collagen + other proteins platelets aggregate and adhere to surface to form temporary plug blood clotting factors form strong, durable thrombin-fibrin clot. Platelets + clotting factors cannot interact w intact endothelium. Clotting factors (i xii are all activated by hydrolysis to #a (activated) form). Thrombosis syndromes: venous thrombosis, mi, stroke, peripheral artery thrombosis. Depletion of functional clotting factors: warfarin, heparin = anticoagulants, also new direct enzyme inhibitors = dabigatrin and rivaroxaban. Inhibits vit k recycling from ko (inactive) to oxidised kh2 (active). Vit k is a cofactor for post- translational carboxylation of glutamic acid groups on factors 2, 7, 9, 10 (tv). Decarboxy- (prothrombin) prothrombin (after post-translational mod = energetically demanding. Vitamin k epoxide reductase complex 1 (vkorc1) recycles vit k back to kh2 form. Warfarin blocks this enzyme, trapping in ko form prevents formation of fibrin clot anticoagulation. Adverse effects: bleeding (coagulation needs monitoring), teratogenic (pregnancy).
