Association between Thromboembolic Events and the <I>JAK2</I> V617F Mutation in Myeloproliferative Neoplasms

Abstract

Thrombotic complications are a major cause of death in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), which are closely associated with the JAK2 V617F activating mutation. However, whether the presence of the JAK2 V617F mutation affects thrombotic risk is currently unknown, although some reports have suggested a variable association with thrombosis. Therefore, we investigated the association between JAK2 V617F and various complications, including thrombosis, in Japanese patients with MPNs. We assessed the JAK2 V617F status in 140 patients who were diagnosed or doubted as having some type of MPN by utilizing a JAK2 V617F-specific guanine-quenching probe. JAK2 V617F was detected in 31 of 51 patients (60.8%) with essential thrombocythemia, all 16 patients (100%) with polycythemia vera, 4 of 11 patients (36.4%) with primary myelofibrosis, 2 of 18 patients (11.1%) with other types of MPNs, and none of the 44 patients with doubted MPN. In the 78 patients with classical MPN, JAK2 V617F correlated with a leukocyte count ≥10,000/μl (p=0.046). Complications of thrombosis, hemorrhage, and leukemic transformation occurred in 21 (41.2%), 4 (25.0%), and 3 (27.3%) patients with classical MPN, respectively, and thrombotic events (TE) occurred more frequently in patients with JAK2 V617F than without (p=0.047). Based on these findings, initial screening for the JAK2 mutation and careful monitoring for thrombotic events should be performed in patients with MPN.

Application of prognostic score IPSET-thrombosis in patients with essential thrombocythemia of a Brazilian public service

“…The lack of correlation between older age and thrombosis was also seen in other recent studies such as those of Lekovic et al 1 and Montanaro et al 20 The presence of JAK2 mutation was not significantly associated with thrombosis in our study, contrary to information well-established in the literature. 14,16,[20][21][22] We believe that our small sample size may explain why we found no correlation between thrombosis risk and the presence of JAK2 mutation.…”

Essential thrombocythemia presenting as digital ischemia

“…Thrombotic event is frequent when JAK2 V617F mutation is present. 10 Most of the time, the platelet count is elevated above 1,000 × 10 9 /L but the studies agree a median level of around 800 × 10 9 / L. 11 Lower levels are usually attributed to inflammation or tissue necrosis.…”

“…9 Te JAK2 V617F mutation is positive in 50-60% of cases. 10 Essential thrombocythemia presents with hemorrhagic complications, due to platelet dysfunction, or thrombotic disorders like stroke, myocardial infarction, venous thrombosis, and digital ischemia. Thrombotic event is frequent when JAK2 V617F mutation is present.…”

Myeloproliferative Disease: An Unusual Cause of Raynaud’s Phenomenon and Digital Ischaemia

“…A typical patient is female and diagnosed in the 5th or 6th decade of life [2]. The JAK2 V617F mutation is identified in 50–60% of cases of ET [3]. …”

“…Thrombotic events occur more frequently in patients with ET who are positive for the JAK2 V617F mutation [3]. The platelet count is often elevated above 1000 × 10 9 /L although studies suggest a median level of around 800 × 10 9 /L at presentation [4].…”