Primary Haemostasis (Figure 7a)

The immediate response to damage of the blood vessel wall is vasoconstriction, which reduces blood flow. This is followed by a sequence of events leading to sealing of the wound by a clot. Collagen in the exposed subendothelial matrix binds von Willebrand factor (vWF), which in turn binds to glycoprotein Ib (GPIb) receptors on platelets, the first stage of platelet adhesion. This initial tethering promotes binding of platelet integrin α₂β₁ and GPVI receptors directly to collagen. Binding of receptors initiates activation, partly by increasing intracellular Ca²⁺. Platelets change shape, put out pseudopodia and make thromboxane A₂ (TXA₂) via cyclooxygenase (COX). TXA₂ releases mediators from platelet dense granules, including serotonin (5-HT) and adenosine diphosphate (ADP), and from α granules vWF, factor V (see below) and agents that promote vascular repair. TXA₂ and 5-HT also promote vasoconstriction. ADP activates more platelets via P2Y₁₂ purinergic receptors, causing activation of fibrinogen (GPIIb/IIIa) receptors and exposure of phospholipid (PLD) on the platelet surface. Plasma fibrinogen binds to GPIIb/IIIa receptors causing the platelets to aggregate (stick together) forming a soft platelet plug (Figure 7a). This is stabilized with fibrin during clotting. Note that thrombin (see below) is also a potent platelet activator.

Formation of the Blood Clot (Figures 7b,c)

The final stage of blood clotting (coagulation) is formation of the clot – a tight mesh of fibrin entrapping platelets and blood cells. The process is complex, involving sequential conversion of proenzymes to active enzymes (factors; e.g. factor X → Xa). The ultimate purpose is to produce a massive burst of thrombin (factor IIa), a protease that cleaves fibrinogen to fibrin. The cell-based model of clotting (Figure 7b) has replaced the older extrinsic and intrinsic pathways. Most of the action in this model occurs on the cell surface (hence its name).

The initial phase of clotting is initiated when cells in the subendothelial matrix that bear tissue factor (TF

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