The megakaryocyte is the hematopoietic cell that produces platelets. Evidence for this relationship was first provided in 1906 by James Homer Wright, who demonstrated that circulating platelets and a giant bone marrow cell now known to be the megakaryocyte shared common tinctorial properties when subjected to a modified Romanofsky stain (picture 1) . Wright went on to show that megakaryocytes sent out pseudopodia into the bone marrow sinusoids from which platelets appeared to be shed .
This model of how megakaryocytes produce platelets remains with us to this day. Wright also demonstrated in normal and abnormal human physiology that changes in platelet number were associated only with changes in the megakaryocytes . Since these seminal observations, much has become known about megakaryocytes and how they produce platelets [3,4]. The characteristics of megakaryocytes, how they regulate platelet production, and their role in pathologic processes will be described here.
In lower vertebrate species such as fish and birds, all the circulating blood cells, including the erythrocytes and the platelets (called thrombocytes), are nucleated and are produced by diploid bone precursor cells . However, in higher vertebrates, platelets are produced by a different mechanism whose evolutionary advantage is unclear. Enucleate platelets are generated from bone marrow megakaryocytes that have a number of unique properties.
In humans, megakaryocytes normally account for approximately 0.05 to 0.1 percent of all nucleated bone marrow cells. Their number increases as the demand for platelets rises. In contrast to the erythrocyte, which has a diameter of 7 to 8 microns and a volume of 85 to 100 fL, megakaryocytes have an average diameter of 20 to 25 microns and a volume of 4700 ± 100 fL (picture 2) . Some of the largest megakaryocytes have diameters of 50 to 60 microns and volumes of 65,000 to 100,000 fL.
Each megakaryocyte produces a total of 1000 to 3000 platelets. Although it has long been assumed that larger megakaryocytes make more platelets, this has never been conclusively demonstrated.