cardiovascular 19 – homeostasis and thrombosis - icsmsu.docVIP

Cardio 19 – Homeostasis and Thrombosis Anil Chopra 1 4. Describe in outline the normal homeostatic mechanisms including interaction of vessel wall, platelets, clotting factors and the fibrinolytic system. Vessel injury. von Willebrand factor in blood plasma leaks out. vWF. Binds to GIpIb or platelet binds directly to collagen fibres without vWF using GIpIa. - Membrane phospholipids converted to thromboxane ADP from platelets. Thrombin from coagulation cascade. Thrombin Activates platelets Synthesises fibrin from fibrinogen Cross-links fibrin to aggregate platelets. (some factors bind to phospholipid exposed on platelet surfaces and this binding is vitamin K dependant. This is inhibited by Warfarin) Once factors VIII and V are activated, they accelerate the membrane dependent reactions. The fibrin clot initiates Fibrinolysis. It does so by activating an enzyme called (tPA) tissue Plasminogen Activator which converts plamsinogen to plasmin. Plasmin breaks down the fibrin clot to release fibrin degradation products (FDP) – tissue Plasminogen Activator (tPA) used in clot busters. N.B. Coagulation is inhibited as the blood coagulation cascade is an amplification. Direct inhibition by antithrombin Antithrombin is an inhibitor of coagulation factors such as Xa, XIa, IXa and thrombin. Its activity is enhanced by heparin sulphates. A drug Heparin enhances antithrombin’s actions. Indirect inhibition by protein C Thrombin binds to receptor on endothelial cell called thrombomodulin. This the activates protein C. Protein C then binds to protein S and together they inactivate factors Va and VIIIa, which downregulate thrombin production. People with factor V Leiden cannot easily deactivate it with protein C so they have increased thrombosis risk. 2 3. Describe the causes of bleeding disorders and the different types. Essentially bleeding disorders are caused by increases in fibrinolytic factors and anticoagulant proteins. They can also be due to deficiency of coagulants. e