The JAK2 Mutation V617F Is Specifically Associated with Idiopathic Splanchnic Vein Thrombosis.
Authors: Régina Sandra , Herault Olivier , D’lteroche Louis , Bacq Yannick , Domenenech Jorge , Binet Christian , Gruel Yves 
Published: October 2019

Abstract
Introduction
Many risk factors have been identified in patients with portal (PVT) and hepatic venous thrombosis (HVT), including myeloproliferative disorders (MPD), i.e. polycythemia vera (PV) and essential thrombocythemia (ET), with prevalence varying between 25% and 65%. Moreover, JAK2 mutation V617F has recently been detected in 65 to 97% of cases of PV and 23 to 57% of ET. The aim of the present study was therefore to evaluate the frequency of JAK2 mutation V617F in a cohort of consecutive patients with PVT or HVT compared to a control group comprising patients with deep vein thrombosis (DVT) of the lower limbs.
Patients and Methods
Forty-four patients with PVT (n=42) or HVT (n=2) diagnosed between 2001 and 2005, and 44 patients (matched for age and gender) with idiopathic DVT were included. The presence of hereditary or acquired risk factors for thrombosis (including FV Leiden and FII G20210A polymorphism, defects in coagulation inhibitors, antiphospholipid antibodies and hyperhomocysteinemia) was investigated in all patients. Bone marrow (BM) biopsy and cultures of blood and BM progenitors were performed in 18 patients with PVT for whom the etiology of thrombosis was undefined. Screening for JAK2 mutation V617F was performed on genomic DNA isolated from peripheral blood cells by an allele-specific PCR and RFLP analysis using BsaXI, as previously described (Baxter et al. Lancet2005, 365:1054), combined with nano-electrophoresis (Bioanalyzer 2100, Agilent) to increase sensitivity. HEL92.1.7 and HL60 cell lines were used as positive and negative controls, respectively.
Results
The 2 groups were similar in terms of blood count and conventional risk factors for thrombosis (Table). JAK2 mutation V617F was detected in 8 patients with PVT (18.2%) but in none with DVT (p=0.003). These 8 subjects had normal blood counts, and no other acquired or hereditary risk factor for thrombosis except for one case exhibiting moderate hyperhomocysteinemia. Bone marrow was hyperplastic in 6/18 patients (all JAK2 V617F positive). Cultures of progenitors showed endogenous erythroid formation in 6/18 cases (all JAK2 V617F positive). The clinical follow-up confirmed the diagnosis of MPD (1 PV and 1 ET) in 2 patients. One subject died in another context and blood counts have remained normal in the 5 other patients to date. The JAK2 mutation V617F was not detected in any patient with negative bone marrow exploration (biopsy and cultures).
Conclusion
The JAK2 mutation V617F is frequently and specifically detected in patients with idiopathic PVT and no other risk factor for thrombosis. Whether JAK2 mutation V617F should be screened in all subjects with splanchnic vein thrombosis and should replace BM biopsy and cultures warrants further studies.
Biological data in patients with PVT/HVT or DVT PVT or HVT (n=44) DVT (n=44) n % 95% CI n % 95% CI p * * Fisher exact test FV Leiden 4 9.1 2.5–21.7 11 25 13.2–40.3 NS FII 20210A 10 22.7 11.5–37.8 6 13.6 5.2–27.4 NS AT, PC, PS deficiency 7 15.9 7.9–29.3 4 9.1 2.5–21.7 NS Antiphospholipid antibodies 5 11.4 4.9–24 8 18.2 9.5–32 NS Hyperhomocysteinemia 4 9.1 2.5–21.7 4 9.1 2.5–21.7 NS JAK2 V617 mutation 8 18.2 9.5–32 0 0 0–8 0.003