Clot Lysis and Intravascular Anticoagulants IBLS LECTURE 10 HAEMOSTASIS II Clot Lysis and Intravascular Anticoagulants 2nd Year Medicine-IBLS Module May 2008

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

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

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 circulating enzyme 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

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

2nd Year Medicine-IBLS Module May 2008

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

Differences between heparin and coumarins Animal origin Plant origin Instant action Delayed (1-2 days) Action lasts for up to 4 hr Lasts for days Given IV or IM Orally Acts by combining to ATIII increasing its effectiveness in removing thrombin and other clotting factors Acts by competitive inhibition of Vit K inhibiting the formation of factors II, VII, IX and X Acts in-vivo and in-vitro Only in-vivo Antidote: protamine sulphate Vitamin K 13

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

2nd Year Medicine-IBLS Module May 2008 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