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PLATELET PRODUCTION, STRUCTURE, AND FUNCTION
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Platelets, like other blood cells, arise from precursors in the bone marrow. Platelet maturation and production from marrow precursors, known as megakaryocytes, is highly regulated by the platelet growth factor, thrombopoietin. Platelet production occurs through the specialized process of endomitosis, by which DNA replicates without cell division, resulting in the polyploid nuclei characteristic of megakaryocytes. Proplatelet extensions form from megakaryocytic cytoplasm; once granule and cytoplasmic organization is complete, platelets are released from the ends of the proplatelets. After leaving the bone marrow, approximately one-third of the platelet mass is sequestered in the spleen, while the remainder circulate in the blood with a life span of 7 to 10 days. Thrombopoiesis is balanced by platelet senescence and consumption to maintain a normal blood platelet count (150,000–400,000/mm3) via plasma thrombopoietin. Platelets have an average diameter of 2.0 to 5.0 µm and typical mean volume of 6 to 10 fL. The platelet external surface consists of a lipid bilayer containing a variety of structural glycoproteins. The anuclear cytoplasm contains abundant alpha granules that contain biologically active proteins including fibrinogen, von Willebrand factor, factor V, and other adhesive molecules. Dense granules are a less abundant but important component of the cytoplasm, and they store and secrete calcium, serotonin, adenosine diphosphate (ADP), and adenosine triphosphate (ATP).
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Circulating platelets have a critical role in hemostasis, through adhesion to sites of vascular injury, amplification of the platelet response, secretion of mediators of hemostasis, and aggregation via fibrinogen binding. After vascular injury, these processes lead to formation of a platelet plug, which constitutes primary hemostasis. Platelets also play a central role in activation of the coagulation cascade, or secondary hemostasis (Fig. 435-1), by providing a phospholipid (cofactor) surface on which several key coagulation reactions take place. For example, the activated platelet surface accelerates the conversion of prothrombin to thrombin by several hundred-thousandfold. Additionally, platelets have many important roles beyond hemostasis, including angiogenesis, innate immunity, and inflammation.
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