hematology and oncology
Overview of Hemostasis
Platelets
Various mechanisms, including endothelial cell nitric oxide and prostacyclin, promote blood fluidity by preventing platelet aggregation and dilating intact blood vessels. These mediators are no longer produced when the vascular endothelium is disrupted. Under these conditions, platelets adhere to the damaged intima and form aggregates. Initial platelet adhesion is to long strings ofvon Willebrand factor(VWF) that have been previously secreted by, and anchored to, stimulated endothelial cells. VWF binds to receptors on the platelet surface membrane (glycoprotein Ib/IX). Platelets anchored to the vessel wall undergo activation. During activation, platelets release mediators of aggregation, includingadenosinediphosphate (ADP) from storage granules. Other biochemical changes resulting from activation include Hydrolysis of membrane phospholipids Inhibition of adenylate cyclase Mobilization of intracellular calcium Phosphorylation of intracellular proteins Arachidonic acid is converted to thromboxane A2; this reaction requires platelet cyclooxygenase and is inhibited irreversibly byaspirinand reversibly by many NSAIDs (nonsteroidal anti-inflammatory drugs). ADP, thromboxane A2, and other mediators induce activation and aggregation of additional platelets on the injured endothelium. Platelet receptors for ADP include the P2Y12 receptor, which sends signals to suppress adenylate cyclase, decreases cyclicadenosinemonophosphate (cAMP) levels, and promotes activation of the glycoprotein IIb/IIIa receptor (assembled on the activated platelet surface membrane from glycoproteins IIb and IIIa). Fibrinogen binds to the glycoprotein IIb/IIIa complexes of adjacent platelets, connecting them into aggregates. Platelets provide surfaces for the assembly and activation of coagulation complexes and the generation ofthrombin.Thrombinconverts fibrinogen into fibrin monomers, and the fibrin monomers polymerize into fibrin polymers that bind aggregated platelets into platelet-fibrin hemostatic plugs. 