Risk Factors and Predictors of Thrombosis in Patients With Philadelphia Negative Myeloprolferative Neoplasms

Classic BCR-ABL negative chronic myeloproliferative neoplasms (MPN) are stem cell disorders characterized by abnormal myeloid proliferation and increased blood cell counts and comprise polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF).

Myeloproliferative neoplasms (MPN) are common malignancies in elderly individuals as the combined annual incidence rates of classical MPNs were reported to be 0.84, 1.03, and 0.47 per 100,000 respectively for PV, ET, and PMF but with a wide variation in prevalence rates reported in different studies. The 5-year relative survival rates are 84.8, 89.9, and 39% for PV, ET and PMF patients, respectively.

Thromboembolic complications represent a major cause of morbidity and mortality in MPN, particularly in PV and ET. The mechanisms underlying increased thrombotic risk in chronic myeloproliferative neoplasms (MPN) are incompletely understood.

Several pathophysiological mechanisms help explain the increased likelihood of thrombosis in these patients. Factors, such as leukocyte and platelet activation leading to the formation of leukocyte-platelet aggregates, activation of the coagulation cascade by microparticles, high levels of inflammatory cytokines, and endothelial dysfunction have a crucial role in thrombosis in MPN patients.

Accurate prediction of the thrombotic risk still represents a challenge and adequate predictive biomarkers are not available. The mechanisms underlying thrombosis involve a complex interplay among blood cells, the endothelium and the coagulation system. Both increased blood counts and cellular activation, which is due to hyperactivation of intracellular signaling pathways and enhanced interaction between blood cells, are implicated in the thrombotic predisposition.