Role of the JAK2 V617F Mutation in Inflammatory Bowel Disease-associated Thromboembolism: Case Report and Review of the Literature

Mutations in the Janus kinase-2 (JAK2) pathway are implicated in myeloproliferative neoplasia (MPN), as well as IBD. In patients without overt MPN, JAK2 mutation is implicated in intra-abdominal thrombosis. Despite this shared genetic predisposition, the role of JAK2 mutation in IBD-associated thromboembolism is not clear. We describe a case of catastrophic arterial thrombosis in an ulcerative colitis (UC) patient with JAK2 V617F mutation. A 62 year old woman presented with 3 months of bloody diarrhea and 15kg weight loss. Inflammatory markers were elevated but her hemogram was normal. Colonoscopy revealed pancolonic edema and erythema but no ulceration or spontaneous bleeding, consistent with moderate UC, Mayo score 2. The patient was started on prednisone and 5-ASA. Her symptoms improved and she was discharged home. She returned in 2 weeks with severe abdominal pain and shock. CT of the abdomen revealed splenic and renal infarcts and extensive thrombus in the common hepatic the superior mesenteric arteries. She underwent an emergent SMA embolectomy and extensive small bowel resection. A thrombophilia work-up revealed a positive JAK2 V617F mutation and warfarin was started. No evidence of MPN was found on bone marrow examination. A comprehensive search of Medline, PubMed, and EMBASE up to November 2016 was performed. We identified three articles related to JAK2 V617F mutations in IBD, comprising 171 patients. In the first study, no JAK2 V617F mutations were identified in 48 IBD with prior thrombotic events. In the second study, 100 IBD patients with no previous thrombotic event or MPN were tested, and no JAK2 V617F mutations were identified. The third study included 23 IBD patients with erythrocytosis or thrombocytosis but no previous thrombotic events. Three cases of JAK2 V617F mutations were identified, exceeding the expected thresholds for statistical significance. In summary, JAK2 V617F mutation is implicated in MPN but its role in IBD-related thrombosis remains unclear. Studies to date do not establish a pathophysiologic link between JAK2 mutations and IBD-related thrombosis. Given the known association between JAK2 V617F mutation and MPN, IBD patients presenting with erythrocytosis or thrombocytosis may benefit from JAK2 mutation testing. IBD patients with large intra-abdominal thrombosis may also benefit from testing for JAK2 mutations as this may alter the duration of anticoagulation treatment.Figure: Kaplan-Meier curves for time to first dose of anti-TNF therapy stratified type of insurance drug coverage. Publicly funded subjects (solid line) experienced longer times to first anti-TNF dose than privately funded subjects (dashed line).Figure: Rates of hospitalizations and emergency department visits stratified by public versus private drug insurance coverage. Additional sensitivity analyses are performed in which the following groups were excluded (excl): those who received first anti-TNF dose as inpatients (Inpt) or through a compassionate use program (Comp); those with private drug insurance coverage who received supplemental public funding (Copay). All rate differences between private and public drug coverage were statistically significant (* p<0.001).

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