Venous thromboembolism related to cytomegalovirus infection: A case report and literature review

RATIONALE: Herein, we present a case of seemingly unprovoked portal vein thrombosis (PVT) occurring in the context of an acute cytomegalovirus (CMV) infection and prolonged debilitating fatigue. PATIENT CONCERNS: A 46-year-old male airline pilot presented with a 2 week history of abdominal pain, nausea, vomiting, watery diarrhea, and daily recurrent fevers. This was in the context of progressive, debilitating fatigue for 3 months forcing the patient to leave his job. DIAGNOSES: Computed tomography of the abdomen revealed PVT, which was managed initially by heparin infusion. Cefepime was ordered for broad-spectrum antibiotic management of sepsis and possible septic thrombosis. Further workup exposed elevated transaminases consistent with mild hepatitis without synthetic dysfunction and colonoscopy revealed colitis. A comprehensive evaluation for liver disease was notable for a markedly elevated ferritin level. Spiking fevers and neutrophilia persisted for several days despite empiric antimicrobial treatment, but eventually resolved. The remainder of the workup was negative except for positive CMV IgM titer and viral load. This raised suspicion for a hypercoagulable state caused by CMV hepatitis with CMV-induced PVT. Heparin was transitioned to warfarin at the time of discharge. INTERVENTIONS: Given the patient's immunocompetent state and resolution of fevers, antiviral therapy for CMV infection was not initiated. OUTCOMES: The patient continued to improve with a normalization of the serum ferritin level and anticoagulation therapy was stopped after 6 months. LESSONS: There is mounting support for infectious causes of venous thromboembolism (VTE) based on existing molecular biology and clinical research. Meta-analysis of existing data showed that between 1.9% and 9.1% of patients hospitalized with VTE had concurrent acute CMV infection. Theoretical mechanisms for this association include transient formation of antiphospholipid antibodies, transient formation of antibodies targeting CMV capsule phospholipids with procoagulant properties, and direct infection of the endothelial cells. We hope this case will serve as a reminder to consider CMV as a transient cause of PVT and VTE, particularly in light of 2016 guidelines for unprovoked VTE recommending lifelong anticoagulation. We also plan to prospectively study the association of unprovoked VTE and acute CMV infection in our own hospital system.