Thrombosis is a leading cause of morbidity and mortality in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Several mechanisms have been proposed to cause or to contribute to the acquired thrombophilic state of these patients, including platelet and red blood cell abnormalities. The increase in white blood cell count, found in most subjects with these disorders, raises the possibility that circulating leukocytes may represent another prothrombotic factor, as demonstrated for other conditions, including sickle cell, coronary heart, and peripheral arterial diseases. Published data demonstrate that neutrophil activation occurs in ET and PV patients in parallel with the appearance of laboratory signs of hemostatic system activation, suggesting an involvement of these cells in the pathogenesis of the thrombotic predisposition of these subjects. In 2005, an acquired point mutation in the pseudokinase domain of Janus kinase 2 (JAK2(V617F)) has been described in these disorders, and has attracted an enormous interest both as a diagnostic and prognostic tool, and as a potential therapeutic target. Retrospective data have identified JAK2(V617F) as a risk factor for thrombosis in ET, and have also shown a close association with abdominal vein thrombosis. JAK2(V617F) is variably associated with thrombosis and, more consistently, with elevations in blood cell counts. A clear link appears to exist between leukocytosis, JAK2(V617F), and the hemostatic system activation in patients with Bcl-negative myeloproliferative disorders.
Copyright 2009 S. Karger AG, Basel.