Propensity for hemorrhage and thrombosis in chronic myeloproliferative disorders

Abstract

Polycythemia vera (PV) and essential thrombocythemia (ET) are two myeloproliferative disorders (MPDs) with frequent thrombotic and hemorrhagic complications. Thrombosis is often the cause of mortality in PV and ET; hemorrhage occurs more commonly in idiopathic myelofibrosis patients, but is rarely fatal. Thromboses may occur in arteries or veins. Splanchnic, portal, hepatic, and splenic vein thromboses are not uncommon and thrombosis is also thought to cause placental vascular insufficiency and fetal wastage during pregnancies in MPD patients. These complications may result because of altered interactions between platelets, white blood cells, or endothelial cells, due to either altered receptor expression, receptor-ligand interactions, or signaling events. Age, leukocytosis, increased hematocrit, and a history of thrombotic events are risk factors for thrombosis. In determining a link between clonality and thrombosis using X-chromosome inactivation patterns in patients with ET, those who were polyclonal were less likely to experience thromboses. The search for hypercoagulability in these patients led to identification of changes in the expression patterns of coagulation proteins from the coagulation cascade. Mutations in factor V Leiden were examined and the incidence of mutations did not vary between normal and MPD patients. However, mutations in factor V Leiden were found to be risk factors for venous thrombotic events. Similarly, presence of a prothrombin gene mutation showed a higher risk for venous thromboembolic events. Proteolyzed thrombospondin appeared to contribute to hypercoagulability, and acquired von Willebrand factor disorder gave rise to hemorrhagic complications. These findings provide several potential reasons for thrombotic and hemorrhagic complications in MPD patients. Therefore, the best therapy for these patients is reduction of their platelet counts to less than 450,000/microL and close regulation of their hematocrits. The role of leukocytosis in bleeding or hemorrhage in this population remains to be elucidated.