2nd year medicine-ibls module may 2008 1 ibls lecture 10 haemostasis ii clot lysis and intravascular...
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2nd Year Medicine-IBLS Module May 2008
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IBLS LECTURE 10
HAEMOSTASIS II
Clot Lysis and Intravascular Anticoagulants
2nd Year Medicine-IBLS Module May 2008
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Objectives
By the end of this lecture the student should be able to:
1. Define fibrinolysis.2. Describe the mechanism of clot lysis.3. Explain how blood clotting is prevented in normal
vascular system (natural intravascular anticoagulants).4. List the major anticoagulants in clinical use.5. Describe the mechanism of action of different
anticoagulants.
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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.
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How is blood clotting in the normal vascular system
prevented?
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Intravascular anticoagulants– Endothelial surface factors:
• Smoothness of the endothelial surface.• Layer of glycocalyx (mucopolysaccharide) which
repels clotting factors and platelets.• Thrombomodulin.
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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?).
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• 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.
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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
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Differences between heparin and coumarins
Heparin 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
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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).
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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?