Thrombocytosis and risk of thrombosis in myeloproliferative neoplasms

In patients with polycythemia vera (PV) and essential thrombocythemia (ET), two Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), thrombotic events are frequent and represent the main cause of morbidity and mortality. Patients with MPN can be stratified in thrombotic risk categories according to age and history of thrombosis. Patients older than 60 years or with a history of thrombosis are considered at high-risk. Recently, new developments have brought to a further subcategorization of patients who are not at high risk in the "intermediate" and "low-risk" categories, depending on the presence or absence of JAK2V617F mutation and/or cardiovascular risk factors. Thrombocytosis is typical of these diseases, particularly of ET, but its role in the pathogenesis of thrombotic events is still controversial. So far, no study has demonstrated a statistically significant correlation between platelet count and thrombosis in either PV or ET patients. Paradoxically, extreme thrombocytosis (i.e., platelets > 1500 × 109/L) is rather associated with hemorrhagic manifestations in patients with ET. Recent biological studies of circulating thrombotic markers performed to characterize the presence of a hypercoagulable state in patients with MPN have shown that platelet qualitative abnormalities, more than platelet count, are associated with hypercoagulability in these patients. Particularly, studies have demonstrated that platelets circulate in an activated status and possess a high prothrombotic potential. These findings suggest that in these diseases the control of platelet activation over the platelet count is an important goal of treatment strategies.