Platelet Physiology
Platelets are essential to the maintenance of primary hemostasis, and a minimum number are required to ensure vascular integrity. Platelets gather and adhere to sites of vascular injury. After doing so, they initiate a hemostatic process by releasing mediators that recruit more platelets to the site.1
Platelets form as cytoplasmic fragments of megakaryocytes found in the bone marrow. In a process regulated by cytokines and chemokines, the entire cytoplasm of the megakaryocyte divides into proplatelets that are released into the circulation. The lifespan of the average platelet is 9 to 10 days. Approximately 35,000 platelets per microliter of blood are produced per day to maintain the average platelet count.1
Several known growth factors are involved with the regulation of platelet production, most importantly thrombopoietin (TPO).1 The term “thrombopoietin” was coined in 1958 to describe the growth factor in the body that causes platelet counts to rise, but it was not until 1994 that this hormone was isolated and identified. TPO is synthesized primarily in the liver. TPO is not stored, but rather produced and immediately secreted.2 Endogenous TPO regulates platelet levels through its binding activity with receptors (TPO-R) found both on platelets and on progenitors of platelets (such as megakaryocytes and hematopoietic stem cells).1
TPO is unlike other hormones—under normal conditions a constant level is produced and its concentration is regulated by its effectors (collectively referred to as “the platelet mass”).2 TPO is cleared from the body by binding to receptors on the platelet surface.1 When there are fewer platelet receptors with which to bind, TPO levels rise and more TPO is free to bind to megakaryocytes and other platelet precursors, driving their differentiation into platelets.1,2
Several hematologic disorders may interfere with this mechanism. In patients with ITP, for example, levels of TPO are not markedly elevated despite the fact that platelet numbers are decreasing due to premature destruction by the reticuloendothelial system (primarily in the spleen).3,4
Read more about treatment for ITP.
References
1. Kaplan RN, Bussel JB. Differential diagnosis and management of thrombocytopenia in childhood. Pediatr Clin N Am. 2004;51(4):1109-1140.
2. Kuter DJ. New thrombopoietic growth factors. Blood. 2007;109(11):4607-4616.
3. Stasi R, Provan D. Management of immune thrombocytopenic purpura in adults. Mayo Clin Proc. 2004;79(4):504-522.
4. Houwerzijl EJ, Blom NR, van der Want JJL, et al. Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood. 2004;103(2):500-506.
