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Lecture 27

Thrombosis and Thrombolysis

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)
Created by: UVAPATH4