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It is uncertain whether the JAK2 V617F mutation increases the thrombotic risk in patients with essential thrombocythemia, and it is unknown whether inherited thrombophilia is an additive risk factor in mutated subjects. We studied 132 patients with essential thrombocythemia, 38 of them (29%) with a history of thrombosis. The JAK2 mutation was present in 83 (63%), and inherited thrombophilia in 7. The mutated patients <60 years had a relative risk (RR) for thrombosis at any time of 3.83 (95%CI 1.27-11.49) in comparison with wild-type patients; in those with both the mutation and thrombophilia the RR was 2.23 (95%CI 1.57-3.18) and 7.66 (95%CI 2.66-22.03) in comparison with mutated or wild-type patients without thrombophilia, respectively. During the follow-up, only the homozygotes for JAK2 V617F were more prone to thrombosis (RR 17.25, 95%CI 2.33-127.4). Among the patients >60 years, no increase in RR was associated with the JAK2 mutation. In conclusion, in the younger patients with ET the thrombotic risk is higher in the JAK2 V617F-mutated and is further increased by the presence of inherited thrombophilia.

Background: Prior thrombosis is a well-established risk factor for re-thrombosis in polycythemia vera and essential thrombocythemia but scarce data are available on the rate of re-thrombosis and the optimal strategy for prevention of recurrence., Design and Methods: We retrospectively estimated the rate of recurrence in a multicenter cohort of 494 patients (poly-cythemia vera/essential thrombocythemia 235/259) with previous arterial (67.6%) or venous thrombosis (31%) or both (1.4%). First thrombosis was cerebrovascular disease in 191 cases, acute coronary syndrome in 106, peripheral arterial thrombosis in 44, and venous thromboembolism in 160. Microcirculatory events were not computed., Results: Thrombosis recurred in 166 patients (33.6%), with an incidence of 7.6% patient-years. Sex, diagnosis (polycythemia vera or essential thrombocythemia), and presence of vascular risk factors did not predict recurrence, whereas age >60 years did (multivariable hazard ratio [HR], 1.67; 95% confidence interval [CI] 1.19-2.32). Increased leukocyte count at the time of the first thrombosis was a risk factor for recurrence in patients <60 years old (HR 3.55; 95% CI 1.02-12.25). Cytoreduction halved the risk in the overall cohort (HR 0.53; 95% CI 0.38-0.73) and the combination with antiplatelet agents or oral anticoagulants was more effective than administration of single drugs. Significant prevention of rethrombosis was independently achieved in patients with venous thromboembolism by both oral anticoagulants (HR 0.32; 95% CI 0.15-0.64) and antiplatelet agents (HR 0.42; 95% CI 0.22-0.77), in those with acute coronary syndrome by cytoreduction (HR 0.30; 95% CI 0.13-0.68), and in those with cerebrovascular disease by antiplatelet agents (HR 0.33; 95% CI 0.16-0.66). The overall incidence of major bleeding was 0.9% patient-years and rose to 2.8% in patients receiving both antiplatelet and anti-vitamin K agents., Conclusions: In patients with polycythemia vera and essential thrombocythemia, cytoreduction protects against recurrent thrombosis, particularly after acute coronary syndrome. The contemporary use of oral anticoagulants (after venous thromboembolism) or antiplatelet agents (after cerebrovascular disease or venous thromboembolism) further improves the protective effect. Such findings call for prospective studies aimed at investigating whether strategies tailored according to the type of first thrombosis could improve prevention of recurrences.

Few data are available on the risk of recurrent venous thromboembolism (VTE) associated with the rare inherited deficiencies of natural anticoagulants. We studied 602 patients with previous VTE: the incidence of first recurrence in the absence of anticoagulation was retrospectively estimated in 64 patients with deficiency of antithrombin (AT, n=14), protein C (PC, n=28), or protein S (PS, n=22) and 538 with no known defect, who acted as the reference group. After adjustment for sex, age, and circumstances of the first event, AT deficiency resulted an independent risk factor for recurrence (hazard ratio 1.9, 95% CI 1.0-3.9); the carriers of PC or PS deficiency had a marginal increase in risk (hazard ratio 1.4, 95% CI 0.9-2.2). In conclusion, patients with AT deficiency are potential candidates for long-term oral anticoagulation.