Platelet Antiaggregant Therapy Prevents Venous Thrombosis in Patients with JAK2 V617F Positive Essential Thrombocythemia without Indication of Cytoreductive Treatment.

Abstract 3906

Poster Board III-842

Essential thrombocythemia (ET) patients under the age of 60 years without history of thrombosis are not considered candidates for cytoreductive therapy. In these patients, risk factors for thrombosis as well as the benefit of platelet antiaggregants are not well established. The aim of the present study was to determine the risk factors for thrombosis in ET patients without indication of cytoreductive therapy and to assess the effect of platelet antiaggregation in thrombosis prevention. For such purpose 300 patients (101 M, 199F) diagnosed with ET at a median age of 39 years (range 5-59) were included in a multicenter retrospective study. Initial treatment consisted of platelet antiaggregants (n=196) or observation (n=104). During a median follow up of 8.6 years (range: 0.2-25), 137 patients initiated cytoreductive therapy being the indication for cytoreduction age > 60 years (n=18), thrombosis (n=25), bleeding (n=13), microvascular symptoms not responding to platelet antiaggregants (n=37), extreme thrombocytosis (n=37) and other (n=7). Median time free of cytoreductive therapy was 4.4 years (Range: 0.1-25). Thrombosis-free survival restricted to the time of cytoreductive therapy abstention was calculated using the Kaplan-Meier method. Variables attaining a significant level at the univariate analysis were included in a Cox proportional hazard model. A total of 32 thromboses (arterial thrombosis: n=21, vein thrombosis: n= 11) were registered during the period of cytoreduction abstention. The probability of survival free of arterial thrombosis was 94% at five years. Elevated serum LDH levels at ET diagnosis and smoking were associated with an increased risk of arterial thrombosis, hazard ratio: 3.1 (CI95%: 1.1-8.3) and 2.9 (CI95%: 1.1-7.9) for LDH and smoking respectively. Age, gender, hypertension, diabetes mellitus, hypercholesterolemia, leukocytosis, thrombocytosis and JAK2 mutational status were not associated with an increased risk of arterial thrombosis. Platelet antiaggregant therapy did not reduce the incidence of arterial thrombosis. The probability of survival free of venous thrombosis was 96% at five years. Patients with JAK2V617F mutation showed and increased risk of venous thrombosis: HR 4.6 (IC95%: 1.1-18.3) whereas platelet antiaggregant therapy resulted in a low risk of venous thrombosis: HR 0.12 (CI95%: 0.03-0.5). When analysis was restricted to patients with the JAK2V617F mutation, the probability of venous thrombosis at 5 years was 96% in those patients receiving platelet antiaggregants and 58% in those patients managed with observation alone (p=0.0006). Platelet antiaggregant therapy was not associated with an increased risk of severe/major bleeding. In conclusion, JAK2V617F-positive ET patients without indication of cytoreductive therapy have an increased risk of venous thrombosis that could be reverted with platelet antiaggregant therapy.