JAK2V617F Mutation Status and Thrombosis in Essential Thrombocythemia

Thrombosis frequently complicates the essential thrombocythemia (ET) and hypercytosis may play a role in the its occurrence as well as the platelet and coagulant activation. Therefore, we evaluated myeloproliferative and platelet and coagulant activation markers such as platelets (plts), white blood cell (WBC), haemoglobin (Hb) and hematocrit (Hct) and β-thromboglobulin (βTG) and platelet factor 4(PF4) and prothrombin fragment 1+2 (F1+2), thrombin-antothrombin (TAT), tissue factor (TF), von Willebrand factor (vWF) and d-dimer (DD), respectively in ET patients and thrombosis. As has been reported that the Janus Kinase 2 (IAK2) V617F mutation gives ET a proliferative advantage, we also evaluated the JAK2 mutation. The study group consisted of fifty ET patients (24 males and 26 females, mean age 58 years) who fulfilled PVSG and WHO. Their mean duration of disease was 7 years. Of 50 patients, 18 were on hydroxyurea whereas 32 were not receiving any cytoreduction. All patients were on antiplatelets. Plts, WBC, HB and HCT were measured by automated analyser. βTG, PF4, F1+2, TAT, TF and DD and vWF were assayed by ELISA and immunoturbimetric assay, respectively. Jak2 mutation was analysed by melt curve analysis. Of 50 patients, 24 were JAK2 V617F-positive and 26 were wild-type (WT). Among JAK2-positive ET, 11 experienced thrombosis including 5 episodes of myocardial infarction (MI), 3 of deep vein thrombosis (DVT), 2 of transient ischemic attack (TIA) and 1 of erytromelalgia (E), whereas of WT ET, 5 developed thrombosis such as 1 DVT, 2 TIA and 2 E. All patients had thrombocytosis (684±299×109/l) and normal WBC (7.8±2.2×109/l) and HB(13±1.8 g/dl) whereas HCT and βTG were higher in JAK2-positive ET than WT (41±5.2 % vs 37±5.2 %) ( p=0.034) (266±83 IU/ml vs 193±18 IU/ml) (p<.0001). PF4 (113±39 IU/ml vs 6.9±2.2 IU/ml), F1+2 (3.4±3.6 nmol/l vs 0.7±0,2 nmol/l), TAT (16.9±28 μg/l vs 2.6±0.9 μg/l) and TF (93±132 pg/ml vs 6.4±2.8 pg/ml) (p<.0001 and p<.0001 and p=0.001 and p<.0001, respectively) were increased in all patients whereas vWF and DD were normal (56±42 % and 185±208 ng/l). There was no correlation between JAK2 mutation and plts and WBC and HB and any activation marker. A positive correlation there was between JAK2 mutation and HCT (p=0.034) and thrombosis (p=0.059). These data suggest that JAK2 V617F mutation is responsible for a hematopoietic expansion which might play a role in the pathogenesis of thrombosis in ET.