Does JAK2 V617F Mutation in Egyptian Patients with First Episode Venous Thromboembolism Contribute to the Hypercoagulable State and Interact with other Thrombophilic Factors

Background: The term thrombophilia includes any inherited and acquired disorders associated with an increased tendency to venous thromboembolism (VTE). Inherited thrombophilia is one of the main determinants of VTE, and the presence of inherited thrombophilic defects exposed carriers to increased risks for VTE compared with non-carriers . The JAK2 V617F mutation is present in the majority of patients with polycythemia vera and essential thrombocythemia, which are myeloproliferative neoplasms frequently associated with arterial and venous thromboembolism. Whether JAK2V617F mutation is associated per se with hypercoagulability remains unclear. Our aim was to clarify the contribution of JAK2V617F to a Hypercoagulable state, as well as its interaction with other thrombophilic factors in patients with venous thrombosis (lower Limb deep venous thrombosis and pulmonary embolism). Material and Methods: The study subjects were 106 Egyptian patients diagnosed as having first episode venous thromboembolism based on Doppler ultrasound +/- computed tomography and pulmonary angiography from January 2010 to December 2011 (54 men and 52 women); median age 39.5; age range from (14-80 years). They were compared with sixty healthy controls sex and age matched. Full history was taken and the clinical and laboratory data were reviewed. All patients and control groups were subjected to assays for factor V Leiden mutation, prothrombin gene mutation G20210A, protein C activity, protein S activity, antithrombin III level, serum homocysteine, anticardiolipin IgG and Ig M antibodies and lupus anticoagulant to evaluate the Hypercoagulable state and the prevalence of JAK2 V617F mutation was detected by two round allele-specific polymerase chain reaction in both patients and control subjects. Samples positive for the mutation were subsequently analyzed via ARMS-PCR. Results: Among the 106 patients, eighty-four had deep venous thrombosis, sixteen had pulmonary embolism and six with concomitant deep venous thrombosis and pulmonary embolism. Twenty five patients were positive for factor V Leiden , three were positive for prothrombin gene mutation ,four had protein S deficiency (three patients had only protein S deficiency and one with factor V mutation) ,six patients had protein C deficiency ,only one had antithrombin III deficiency. Fourteen patients were positive for anticardiolipins and seven for lupus anticoagulant (2 patients were positive for lupus anticoagulant alone and five with positive anticardiolipins) and seven had hyper-homocysteinemia. Jak2V617F mutation was detected in six patients (5.7%) and was positive in two subjects in the control group(3.3%). Conclusion: Factor V Leiden is the most common inherited thrombophilic defect in Egyptians. The presence of inherited thrombophilic defects exposed carriers to increased risks for VTE compared to non carriers . The prevalence of jak2 V617F mutation in one hundred and six Egyptians presenting with first episode venous thromboembolism is low (5.7%) and is statistically insignificant in comparison to the controls and has no association with any of the thrombophilic risk factors. (Shereen M. EL-Maghraby and Ahmed M. L. Bedewy. Does JAK2 V617F Mutation in Egyptian Patients with First Episode Venous Thromboembolism Contribute to the Hypercoagulable State and Interact with other Thrombophilic Factors? Life Sci J 2012;9(2):254-262). (ISSN: 1097-8135). http://www.lifesciencesite. com. 40