Megakaryocytopoiesis : The megakaryocyte/platelet haemostatic axis

Megakaryocytes as the precursor of platelets are essential for the maintenance of haemostasis. Platelets are heterogeneous for size and reactivity and large platelets are more haemostatically active than small platelets (Thompson et al. 1982). This platelet heterogeneity arises at thrombopoiesis (Martin et al. 1983). Several studies suggest that platelets are involved in experimentally produced atherosclerosis (Fuster et al. 1978; Harker et al. 1976), and many large scale clinical trials provide convincing evidence for the role of platelets in acute ischaemic syndromes (Lewis et al. 1983; ISIS-2 1988). Furthermore, the presence of more reactive platelets (i.e. patients with a raised mean platelet volume, MPV) 6 months after a first myocardial infarction (MI) is a powerful predictor of either death or a further ischaemic event (Martin et al. 1991). Platelet organelles and enzyme systems are created in the megakaryocyte and changes in platelet volume and reactivity are correlated with and preceded by changes in the megakaryocyte. Therefore, perturbations of megakaryocyte physiology may have important pathological implications for the development of atherosclerosis and thrombosis, which remain a major cause of morbidity and mortality in the Western world. Furthermore, abnormalities of megakaryocyte number and function can lead to haemorrhagic disease.