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Lecture 27
Thrombosis and Thrombolysis
Question | Answer |
---|---|
What are the physical properties that help retard clot formation in uninjured blood vessels? | 1)Lamellar flow of blood in vessels 2)Negative charge of endothelial cells and platelets 3)Endothelial cells shield platelets from collagen and other pro-aggregatory components of sub-endothelial layer |
What is the anticoagulant function of Heparan sulfate found on the surface of endothelial cells? | Catalyzes antithrombin (ATIII) inactivation of coagulation enzymes |
What is the anticoagulant function of tissue plasminogen activator released from the endothelium? | Breaks down inadvertently formed fibrin |
What is the mechanism of anticoagulation of tissue factor pathway inhibitor? | Tissue factor pathway inhibitor (TFPI) binds to Factor Xa. TFPI/Xa binds to tissue factor/FVII, forming a quaternary complex. |
How does antithrombin (ATIII) inhibit activated clotting factors? | ATIII is attracted to the negatively charged catalyst heparin on the surface of endothelial cells. This induces a conformational change that now is able to bind thrombin and other serine proteases (XI, IX, X) and inactivate them. |
What is the mechanism of heparin? | Heparin binds ATIII inducing a conformational change enabling ATIII to bind to thrombin and other proteases. The rate of inactivation by ATIII is increased by up to 1000-fold by heparin, which acts as a catalyst. |
What is the minimum number of saccharide subunits of heparin required for inactivation of thrombin? | 18 |
How is D-Dimer generated? | It is a product of fibrin breakdown by plasmin. |
What is the function of alpha-2-plasmin inhibitor? | It binds and clears free plasmin. |
What is the function of Plasminogen activator inhibitor-1 (PAI-1)? | It binds and clears tPA |
What stimulates tPA release by endothelial cells? | Fibrin |
Pathophysiology of Dysfibrinogenemia | A defect of fibrinolysis resulting from fibrin that lacks tPA/Plasminogen binding sites rendering it resistant to degradation by Plasmin. |
What is Virchow's triad? | Describes 3 factors that contribute to venous thrombosis: 1) Alterations in normal blood flow (stasis) 2) Injury to the vascular endothelium 3)Alterations in the constitution of blood (hypercoagulable state) |