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IBLS LECTURE 10. HAEMOSTASIS II Clot Lysis and Intravascular Anticoagulants. Objectives. By the end of this lecture the student should be able to: Define fibrinolysis . Describe the mechanism of clot lysis .
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IBLS LECTURE 10 HAEMOSTASIS II Clot Lysis and Intravascular Anticoagulants 2nd Year Medicine-IBLS Module May 2008
Objectives • By the end of this lecture the student should be able to: • Define fibrinolysis. • Describe the mechanism of clot lysis. • Explain how blood clotting is prevented in normal vascular system (natural intravascular anticoagulants). • List the major anticoagulants in clinical use. • Describe the mechanism of action of different anticoagulants. 2nd Year Medicine-IBLS Module May 2008
Lysis of Blood Clots- Fibrinolysis • •Fibrinolysis: is the process of clot dissolution. • Plasminogen (profibrinolysin), a plasma protein, becomes trapped in the clot. • Damaged tissues and vascular endothelium slowly release tissue plasminogen activator (t-PA) that converts plasminogen into plasmin (fibrinolysin). • Plasmin digests the fibrin threads and other clotting factors and removes the clot. 2nd Year Medicine-IBLS Module May 2008
How is blood clotting in the normal vascular system prevented? 2nd Year Medicine-IBLS Module May 2008
Intravascular anticoagulants • Endothelial surface factors: • Smoothness of the endothelial surface. • Layer of glycocalyx (mucopolysaccharide) which repels clotting factors and platelets. • Thrombomodulin. 2nd Year Medicine-IBLS Module May 2008
Intravascular anticoagulants • Antithrombin Action of fibrin and antithrombin III: • Fibrin fibers: during clot formation thrombin becomes adsorbed to fibrin fibers which prevents excessive spread of clot. • Antithrombin III a circulatingenzyme inhibitor that binds to thrombin and other activated clotting factors (factors IX, X, XI, and XII) and blocks their activity. This binding is facilitated by heparin (source?). 2nd Year Medicine-IBLS Module May 2008
Q: Why doesn’t the platelet plug continue to develop and expand over the surface of adjacent normal vessel lining? • A: The normal endothelium releases nitric oxide (NO) & prostacyclin (PGI2) which inhibit platelet aggregation so that the platelet plug is limited to the defect and does not spread to normal vascular tissue. 2nd Year Medicine-IBLS Module May 2008
Anticoagulants for clinical use • In-vivo (inside the body) • IV: Heparin • Oral: Coumarins (e.g. dicumarol and warfarin). • In-vitro (outside the body) • Heparin • Calcium-deionizing agents 2nd Year Medicine-IBLS Module May 2008 12
In-vitro anticoagulants • Siliconized containers: prevent contact activation of intrinsic clotting system. • Heparin • Calcium-deionizing agents: • Oxalate compounds:precipitation of calcium oxalate (toxic so cannot be used for blood transfusion). • Citrate compounds:combines with calcium in the blood and gives an un-ionized calcium compound (can be used in blood transfusion). 2nd Year Medicine-IBLS Module May 2008 14
Summary Describe the process of clot lysis (fibrinolysis) that reopens a blocked vessel. What are the natural intravascular anticoagulants that prevent clotting in the normal vascular system? What are the anticoagulants used in the clinical practice and what is their mechanism of action? 2nd Year Medicine-IBLS Module May 2008