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Leukocytosis and Thrombosis

White blood cell count has previously been linked to the incidence of thrombosis in the general population. Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative disorders which are considered hypercoagulable states, due to the high incidence of thrombotic complications, associated with high morbidity and mortality. Ten percent to 30% of patients with these disorders present with major thrombotic complications, and a similar proportion develop a thrombotic complication during their disease course. Arterial thromboses, especially affecting the cerebral or coronary arteries, are more common than venous thromboses. Recent studies on the pathogenesis of thrombosis in myelo-proliferative disorders have suggested a role for leukocyte activation, and leukocyte interaction with platelets and endothelial cells. Two recent studies investigated a possible association between leukocyte count and thrombosis in PV and ET.

In PV, major known risk factors for thrombosis include age over 65 years and previous thrombotic history. A recent study (Blood. 2007;109:2446-2452) analyzed the role of other potential risk factors, including white blood cell count and classic cardiovascular risk factors, in a large database of 1638 patients with PV. Patients with a white blood cell count >15,000/uL had a significant increase in the risk of thrombosis compared with those with a white blood cell count below 10,000/uL, mainly due to an increased risk of myocardial infarction (hazard ratio 2.84). Smoking was also associated with an increased risk of arterial thrombotic events.

In ET, age over 60 years and prior thrombotic events are known independent predictors of vascular complications. These two factors are widely used to stratify thrombotic risk in these patients for cytoreductive drug treatment decisions. A recent study (Blood. 2007;109:2310-2313) of 439 patient with ET investigated whether an increased white blood cell count was associated with thrombosis, and whether this effect could be modulated by cytoreductive therapy. The authors reported that a white blood cell count greater than the median value (8,700/uL) at diagnosis was associated with an increased risk of thrombosis during follow-up (hazard ratio 2.3), and that hydroxyurea-induced lowering of the white blood cell count was associated with a reduction of this thrombogenic risk. The presence of JAK2 mutation was not identified as a risk factor for thrombosis in this study, despite a significant association between the mutation and leukocytosis.

Interestingly, neither hematocrit nor platelet count elevations influenced thrombotic risk in either PV or ET. In summary, leukocytosis is a significant risk factor for thrombosis in PV and ET. The authors of these studies suggest that leukocyte count should be considered in defining vascular risk in patients with myeloproliferative disorders, and should be taken into account as an additional factor in cytoreductive treatment decisions. Validation of these findings in prospective studies is indicated.

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