Primary hemostasis is defined as the formation of the primary platelet plug and involves platelets, the blood vessel wall and von Willebrand factor. As a general rule, abnormalities in primary hemostasis result in hemorrhage from mucosal surfaces (epistaxis, melena, hematuria), petechial or ecchymotic hemorrhages, and prolonged bleeding after venipuncture or wounds. However, if the defect is severe, bleeding more typical of disorders of secondary hemostasis, can result, e.g. intracavity hemorrhage. Therefore, an animal presenting with clinical signs typical of a defect in primary hemostasis may have abnormal platelet number or function, abnormal von Willebrand factor or defects in the blood vessel wall (the latter are very rare).|
The normal endothelium prevents hemostasis by providing a physical barrier and by secreting products which inhibit platelets, including nitric oxide and prostaglandin I2 (prostacyclin). Following injury to the vessel wall, the initial event is vasoconstriction, which is a transient, locally-induced phenomenon. Vasoconstriction not only retards extravascular blood loss, but also slows local blood flow, enhancing the adherence of platelets to exposed subendothelial surfaces and the activation of the coagulation process. The formation of the primary platelet plug involves platelet adhesion followed by platelet activation then aggregation to form a platelet plug. Click here for a visual representation of primary hemostasis.
Platelets also contribute to secondary hemostasis (coagulation cascade) by providing a phospholipid surface (this used to be called PF3) and receptors for the binding of coagulation factors.
- Platelet adhesion: The first event in hemostasis is the adhesion of platelets to exposed subendothelium. In areas of high shear rate (in the microvasculature), this is mediated by von Willebrand factor (vWf), which binds to glycoprotein Ib-IX in the platelet membrane. In areas of low shear rate (e.g. aorta), fibrinogen mediates the binding of platelets to the subendothelium (by attaching to a platelet receptor - the integrin, glycoprotein Ia/IIa).
- Platelet activation: The adhesion of platelets to the vessel wall activates them, causing the platelets to change shape, to activate the collagen receptor on their surface (an integrin receptor called glycoprotein IIb/IIIa) and to undergo the release reaction (release alpha and dense granule constituents). In addition, upon activation, platelets synthesize and release thromboxane A2 (TXA2) and platelet activating factor (PAF), which are potent platelet aggregating agonists and vasoconstrictors.
- Platelet aggregation: Thromboxane2, PAF, ADP and serotonin (ADP and serotonin are released from dense granules) are platelet agonists, causing the activation and recruitment of additional platelets, which bind to the adhered platelets. This activation is enhanced by the generation of thrombin through the coagulation cascade; thrombin being an important platelet agonist. Platelet aggregation is mediated primarily by fibrinogen (vWf has a secondary role), which binds to glycoprotein IIb/IIIa on adjacent platelets. This aggregation leads to the formation of the primary platelet plug, which must be stabilized by the formation of fibrin.