Prevalence of the JAK 2 V 617 F mutation associated with splanchnic vein thrombosis . A 10-year retrospective study

Thromb Haemost 2009; 101: 787–789 Dear Sir, Recent works reported a high prevalence of JAK2 V617F mutation in patients with splanchnic vein thrombosis (SVT) including Budd-Chiari Syndrome (BCS) and portal venous system thrombosis (PVT) (1–6), leading to suspect an underlying myeloproliferative disease (MPD). We have performed a retrospective study on patients with SVT followed-up at Montpellier University Hospital over a period of 10 years (1996–2006). The aim was to determine JAK2 V617F mutation status and the risk for subsequent development of MPD. We investigated patients with SVT that underwent screening for thrombophilia at least three months after the thrombotic event. Inclusion criteria were the following: adult patients with diagnosis of BCS or PVT, absence of known causes of SVT such as malignancies or cirrhosis, available DNA for molecular testing gathered during thrombophilia screening. Patients who had established criteria for MPD (7, 8) at the time of thrombosis were excluded. Informed consent to study their DNA was obtained from all patients. Collection and use of blood samples was approved by the local Ethics Committees. The JAK2 V617F mutation was detected by single polymorphism genotyping assay using real-time quantitative polymerase chain reaction (PCR) (9) on leukocytes genomic DNA. Proportion of JAK2 V617F allele burden for positive samples was determined by allele-specific semi-quantitative PCR (JAK2 MutaScreen® Kit, Ipsogen, Marseille, France). Forty-three cases of SVT were analysed (2 BCS, 41 PVT). Our series included 25 females (58.1%) and 18 males (41.9%). Mean age at diagnosis was 47 years (18–78). We detected JAK2 V617F mutation in 9.3% of all patients (n=4). The four patients with mutation were women, 24– to 65-years-old at the time of thrombosis, with diagnosis of PVT. No significant difference was found concerning age at diagnosis of SVT, sex or presence of a splenomegaly. Peripheral blood cells count was in the normal range in most patients of the whole cohort. We found that JAK2 V617F mutation was associated with higher white blood cells (WBC) and platelets count (p<0.05, Table 1) but not with higher haemoglobin levels. A prothrombotic risk factor was present in 32.6% of cases (n=14). The most frequent was factor VIII excess, defined as persistent elevated levels of factor VIII more than 200%, not related to an inflammatory state (11.6%). We also found antiphospholipid antibodies (lupus anticoagulant or anticardiolipin, beta2-glycoprotein I dependant antibodies) (9.3%), factor II 20210A polymorphism (9.3%), and factor V Leiden variant (2.3%). No protein C, S or antithrombin deficiencies were detected. A thrombophilic factor was found in two patients with JAK2 V617F mutation (factor II 20210A polymorphism in one case, antiphospholipid antibodies and factor VIII excess in the other case). Clinical risk factors of thrombosis such as surgery, trauma, immobilisation, plaster cast, pregnancy and post-partum, oral contraception, chronic digestive inflammatory disease, were observed in five patients of the overall cohort (11.6%). Among them, three carried the JAK2 V617F mutation. Thirty-three patients (76.7%) had a personal previous history of thrombosis at the time of SVT. Thirteen patients (30.2%) had a familial history of thrombosis. The follow-up has been performed for the four patients with the JAK2 V617F mutation. Overt MPD developed in three of