A case of severe gastrointestinal bleeding unmasking a JAK2-positive myeloproliferative neoplasm

Myeloproliferative neoplasms (MPNs), particularly those driven by JAK2 V617F mutations, are a well-established yet frequently underrecognized cause of splanchnic vein thrombosis. Thrombosis may precede classic features such as elevated blood counts or splenomegaly and serve as the first sign of clonal hematopoiesis. We present a case of a young man with no prior medical history who presented in hemorrhagic shock due to gastrointestinal bleeding from portal hypertension secondary to extensive splanchnic thromboses, ultimately found to have a JAK2-positive MPN.

A 31-year-old previously healthy man was found in hemorrhagic shock with a hemoglobin of 5.7 g/dL, requiring massive transfusion and vasopressors. Initial laboratory workup was notable for white blood cell count of 30.8 K/uL, platelets 1078 K/uL, INR 1.9, fibrinogen 103 mg/dL, creatinine 1.4 mg/dL, and lactate 12 mmol/L. Liver function tests showed mild transaminitis (AST 70 IU/L, ALT 36 IU/L) and hyperbilirubinemia (total 5.4 mg/dL; direct 2.2 mg/dL). A phosphatidylethanol level of 21 suggested mild alcohol use. Additional workup, including EBV, ceruloplasmin, hepatitis, and autoimmune panels, was unremarkable. CT revealed splenomegaly and chronic portal vein thromboses with multiple perigastric, gastroesophageal, and rectal venous collaterals. Liver ultrasound revealed coarsened echotexture and an atrophic appearance suggestive of cirrhosis. Esophagogastroduodenoscopy showed gastric varices. He underwent emergent gastric and splenic artery embolization, later followed by balloon-occluded retrograde transvenous obliteration and transjugular intrahepatic portosystemic shunt for portal decompression.

Hypercoagulable workup revealed a JAK2 V617F mutation. His course was complicated by upper extremity thromboses, seizures with cerebral edema and microhemorrhages, and ESBL Klebsiella infection. He developed marked leukocytosis (WBC >60 K/uL), initially attributed to stress and infection, but persisted despite antibiotics. Hydroxyurea was initiated for persistent leukocytosis and JAK2 positivity. Bone marrow biopsy is pending.

This case highlights a rare and dramatic initial presentation of JAK2-positive MPN, emphasizing the importance of considering MPNs in patients with unexplained SVT. It also underscores the complexity of managing concurrent bleeding and thrombotic risks in early disease, especially in the setting of neurovascular complications.