Gain-of-function gene mutations and venous thromboembolism: distinct roles in different clinical settings

Objective To calculate the prevalence of common gain of function gene mutations in patients with different clinical manifestations of venous thromboembolism Design Case-control study Setting Two hospitals in Italy Participants 387 patients with venous thromboembolism and 286 controls Main measures factor V Leiden, factor II A20210, and JAK2 V617F mutations Main results Among patients with deep vein thrombosis in one leg, 23 (20.9%) carried factor V Leiden and factor II A20210 mutations. Similar figures were observed in patients with cerebral vein thrombosis (n=9; 20.0%) and among patients presenting with splanchnic vein thrombosis (n=26; 18.7%). A lower prevalence was obtained in patients with retinal vein thrombosis (n=11; 11.8%). The JAK2 F617 mutant allele was found in 27 patients with splanchnic venous thrombosis (21.1%), and in none of the patients with a thrombotic event in different districts. Thirteen of the 27 JAK2 V617F-positive subjects with splanchnic venous thrombosis were previously known to have a myeloproliferative disease. Three other patients had a diagnosis of myeloproliferative disease after the occurrence of the thrombotic event Conclusion Carriership of factor V Leiden or factor II A20210 mutations identifies an at-risk condition for venous thrombosis in the lower extremities, splanchnic or cerebral vein thrombosis. In patients with splanchnic venous thrombosis, screening for the JAK2 V617F mutation may be useful to recognize patients who should be carefully observed for the subsequent development of overt myeloproliferative disease. Thus, genetic tests may play a different role, various clinical manifestations of venous thromboembolism being associated with distinct risk profiles.