1. Coagulation Just the basics...

2. Three steps Vasoconstriction Platelet plug formation Fibrin clot formation

3. Essentially all interconnected and all occurring at the same time.

4. Platelet plug formation Step 1 – covering the exposed surfaces Mechanism: Adherence of platelet GP1b to von Willebrand factor. vWF is in turn bound to collagen.

5. Step 2: Platelet activation Shape change – discoid to spiny Membrane flip-flop – become negatively charged Assemble GPIIb IIIa receptors for fibrinogen Release some coagulation factors from alpha granules Release ADP from dense granules

6. Platelet aggregation

7. Initiation of coagulation cascade Tissue factor + Factor VII = firelighter

8. The coagulation cascade “Intrinsic” pathway = Main fuel of fire

9. Interactions Platelets Shape change Membrane flip flop Alpha granule release Platelet activation ADP release Coagulation cascade Surface area for reaction Negative charge for docking factors Increased concentration of factors Thrombin production

10. Inhibition of coagulation Tissue factor pathway inhibitor (TFPI) Antithrombin Protein C/ Protein S

11. Role of the endothelium in inhibition of thrombosis Antithrombin and heparin Thrombomodulin and Protein C Prostacyclin Nitric oxide Release of fibrinolytic activators (TPA) Blood flow in intact vessels washes away thrombin