Megakaryocytes: origin of bleeding and thrombotic disorders.

Thrombocytes of lower vertebrates are nucleated diploid cells, which differentiate directly from stem cells without an interposed megakaryocytic maturation program. With increased complexity of circulatory systems and higher blood pressures, more efficient haemostasis was required. In higher vertebrates and man, megakaryocytes developed which, by way of endomitotic polyploidization, can amplify genes relevant for haemostasis and adapt platelets to different haemostatic demands. As endomitotic polyploidization is regulated by cytokines, it is also influenced by inflammatory or malignant cell growth. The responsiveness of the megakaryocyte system to various stimuli is a possible explanation for the high incidence of thrombohaemorrhagic and thromboembolic disorders in man. For example, thrombotic complications in tumour patients are due to pathologic overstimulation of megakaryocytes. Atherosclerosis is another process which may be caused by inappropriate stimulation of the megakaryocyte system. As this complication does not manifest itself during reproductive ages, it is not going to be corrected by evolution.