Coagulation

Just the basics...

Three steps

• Vasoconstriction• Platelet plug formation• Fibrin clot formation

Essentially all interconnected and all occurring at the same time.

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.

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

Platelet aggregation

Initiation of coagulation cascade

Tissue factor

+Factor VII

=firelighter

The coagulation cascade

“Intrinsic” pathway=

Main fuel of fire

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

Inhibition of coagulation

• Tissue factor pathway inhibitor (TFPI)

• Antithrombin

• Protein C/ Protein S

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