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– Measures thrombin induced conversion of fibrinogen to fibrin. – Prolonged in states of decreased fibrinogen or presence of anticoagulants including fibrin degradation products (FDP). – Useful screen for hypofibrinogenemia but complicated by marked sensitivity to heparin. • Thrombin time Assessment of coagulation • Heterogeneous group of disorders. • Factor levels must be significantly below normal before screening tests (PT, PTT) are prolonged. • Personal or family history of spontaneous bleeding important clues. • Pre-op replacement therapy guided by serum factor levels. Disorders of cascade – DDAVP – FFP and cryoprecipitate. – Plasma-based vs. recombinant factor VIII. • Sex-linked recessive, 1:10,000 male births. • Prolonged PTT (nl PT, bleeding time, vWF). • >5% levels rarely bleed spontaneously, <2% present with severe bleeding. • Treatment Hemophilia A (VIII) • Caution for increased risk of thrombosis during treatment. – Prothrombin complex concentrate. – High-purity Factor IX. • Normal PT and prolonged PTT. • Treatment Hemophilia B (IX) – Exposed subendothelium potent stiumulus for platelet adherence. – vWF binds platelets. Thromboxane A2. Serotonin. – Vasoconstriction most pronounced in arteries. • Continous, active, 1000 m2 barrier. • Healthy endothelium resistant to platelet aggregation (secretes prostacyclin, PGI2). • Subendothelial matrix composed of collagen, elastin, fibronecetin, thrombospondin, mucopolysaccharides, vWF. Endothelium • Protein C inactivates Va and VIIIa and neutralizes PAI-1 (plasminogen-activator inhibitor). – Binds thrombin and inactivates. – Complex potentiates protein C activation. • Thrombomodulin – Endothelium with cell surface molecules similar to heparin. – Activation by heparin increases rate 10000 fold. – Inhibits thrombin, factor Xa, IX, XI, XII. • Antithrombin III Anti-thrombogenic role Endothelium Virchow’s Triad • Allows remodeling and removal of thrombus. Fibrinolytic System – Complexes with plasminogen. – May elicit profound allergic response. – Least expensive. • Streptokinase – Responsible for fibrinolytic property of urine. – Intermediate cost. • Urokinase-type (uPA) – Binds avidly to fibrin. – Expensive. • Tissue-type plasminogen (tPA) Plasminogen Activators