Microvascular disturbances, thrombosis, and bleeding in thrombocythemia: current concepts and perspectives

Although ET is a relatively rare disease and, in general, life expectancy of patients is similar to that of individuals without the disease, hemostatic complications are the major causes of mortality and morbidity in some patients. Hemostatic complications are most likely due to as yet poorly defined abnormalities in platelet-vessel wall interactions. Treatment modalities used in the past include cytoreductive therapy and antiplatelet therapy, although the basis of their use has been, until recently, only retrospective observations and not prospective, randomized clinical trials. The older therapeutic modalities, such as radiophosphorus (32P) and alkylating agents, have been largely abandoned because of their leukemogenic potential. The leukemogenic potential of hydroxyurea, presently the most widely used cytoreductive agent, remains uncertain. Interferon-alpha and anagrelide are promising newer drugs. However, because of the toxicity of these agents, there is a pressing need for prospective, controlled clinical trials to establish the indications for cytoreductive and antiplatelet therapy in different subsets of patients with ET. Ultimately, it can be anticipated that elucidation of the molecular basis of ET will permit specific targeting of therapy to the pathogenetic megakaryopoietic defect(s) in the disease.