The approximately 1 trillion platelets that circulate in an adult human are small anucleate cell fragments adapted to adhere to damaged blood vessels, to aggregate with one another, and to facilitate the generation of thrombin. These actions contribute to hemostasis by producing a platelet plug and then reinforcing plug strength by the action of thrombin converting fibrinogen to fibrin strands. To accomplish these tasks, platelets have surface receptors that can bind adhesive glycoproteins; these include the GPIb/IX/V complex, which supports platelet adhesion by binding von Willebrand factor, especially under conditions of high shear, and the αIIbβ3 (GPIIb/IIIa) receptor, which is platelet-specific and mediates platelet aggregation by binding fibrinogen and/or von Willebrand factor. Other receptors for adhesive glycoproteins (integrin α2β1 [GPIa/IIa], GPVI, and perhaps others for collagen; integrin α5β1 [GPIc*/IIa] for fibronectin; integrin α6β1 [GPIc/IIa] for laminin; and CLEC-2 for podoplanin) also contribute to platelet adhesion, but their precise contributions are less well defined. Activated platelets express both surface P-selectin, which mediates interactions with leukocytes, and CD40 ligand, which activates a number of proinflammatory cells, and release chemokines and a soluble form of CD40 ligand, thus initiating an inflammatory reaction. Platelet coagulant activity results from the exposure of negatively charged phospholipids on the surface of platelets and the generation of platelet microparticles, along with release and activation of platelet factor V and perhaps exposure of specific receptors for activated coagulation factor. Platelets change shape with activation as a result of a complex reorganization of the platelet membrane skeleton and cytoskeleton. With activation, platelets undergo release of α granules, dense bodies, and lysosomes, the contents of which work to restore vascular integrity. The activation process involves a number of receptors for agonists such as adenosine diphosphate, epinephrine, thrombin, collagen, thromboxane (TX) A2, vasopressin, serotonin, platelet activating factor, lysophosphatidic acid, sphingosine-1-phosphate, and thrombospondin, as well as several signal transduction pathways, including phosphoinositide metabolism, arachidonic acid release and conversion into TXA2, and phosphorylation of a number of different target proteins. Increases in intracellular calcium result from, and further contribute to, platelet activation. Platelet activation results in a change in the conformation of the integrin αIIbβ3 receptor, leading to high-affinity ligand binding and platelet aggregation.
Platelets also act as storehouses for a variety of molecules that affect platelet function, inflammation, innate immunity, cell proliferation, vascular tone, fibrinolysis, and wound healing; these agents are actively released upon platelet activation. Other vasoactive and platelet-activating substances are newly synthesized when platelets are activated. Through cooperative biochemical interactions, platelets can communicate with, and are affected by, other blood cells and endothelial cells.
Quantitative and qualitative disorders of platelets produce hemorrhagic diatheses (Chaps. 9 to 12). In pathologic states, uncontrolled platelet thrombus formation can lead to vasoocclusion and ischemic tissue necrosis, as, for example, in myocardial infarction and stroke (Chap. 25). Platelets may also facilitate tumor cell growth ...