Thrombosis and bleeding in polycythemia vera and essential thrombocythemia: Pathogenetic mechanisms and prevention

Abstract

Polycythemia vera and essential thrombocythemia are chronic myeloproliferative disorders, the benign clinical course of which can be complicated by both thrombotic and hemorrhagic diatheses. Thrombotic diathesis is characterized by microcirculatory disturbances and by an increased risk of arterial and venous thromboses. Thrombotic accidents often manifest at diagnosis or in the preclinical phase of the disease so that the search for a latent myeloproliferative disorder has become widely recommended in screenings for acquired thrombophilia, particularly when venous thromboses manifest at an unusual site. Hemorrhagic diathesis is more rare, less ominous and mostly affects patients with a very high platelet count. In these subjects, an altered degradation and function of von Willebrand factor can cause minor mucocutaneous hemorrhages, which are sometimes a prelude to major gastrointestinal bleedings. The bleeding tendency can be effectively treated by cytoreduction. Pathogenesis and treatment of thrombotic diathesis are still controversial. The nature of disease-related hemostatic abnormalities and the role of common risk factors are far from being elucidated. In polycythemic subjects, treatment of blood hyperviscosity is essential and low-dose aspirin, which has an established antithrombotic efficacy, should always be used in the absence of contraindications. These are mostly constituted by conditions of increased bleeding risk, which, in particular, have to be evaluated when considering aspirin use in patients with essential thrombocythemia. Future clinical research should primarily aim to assess the risk/benefit ratio of aspirin use in this disease, to better characterize the determinants of vascular risk and to reduce the high incidence of leukemias in patients with these diseases. This might require either the availability of safer cytoreductive agents or, alternatively, the use of more aggressive antiplatelet regimens in patients at high thrombotic risk.