Interpreting the developmental dance of the megakaryocyte: a review of the cellular and molecular processes mediating platelet formation

Abstract

Platelets are essential for haemostasis, and thrombocytopenia (platelet counts <150×10(9) /l) is a major clinical problem encountered across a number of conditions, including immune thrombocytopenic purpura, myelodysplastic syndromes, chemotherapy, aplastic anaemia, human immunodeficiency virus infection, complications during pregnancy and delivery, and surgery. Circulating blood platelets are specialized cells that function to prevent bleeding and minimize blood vessel injury. Platelets circulate in their quiescent form, and upon stimulation, activate to release their granule contents and spread on the affected tissue to create a physical barrier that prevents blood loss. The current model of platelet formation states that large progenitor cells in the bone marrow, called megakaryocytes, release platelets by extending long, branching processes, designated proplatelets, into sinusoidal blood vessels. This review will focus on different factors that impact megakaryocyte development, proplatelet formation and platelet release. It will highlight recent studies on thrombopoeitin-dependent megakaryocyte maturation, endomitosis and granule formation, cytoskeletal contributions to proplatelet formation, the role of apoptosis, and terminal platelet formation and release.