Venous thromboembolism related to cytomegalovirus infection

Abstract

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.

Cytomegalovirus-Associated Venous and Arterial Thrombotic Disease

“…Current guidelines recommend transient or reversible causes of VTE be treated with anticoagulation for 3 months, whereas unprovoked VTE is treated with extended anticoagulation unless the bleeding risk is high [ 7 ]. We suspect that CMV-associated VTE is likely underrecognized because CMV testing is not routinely performed outside of immunocompromised populations [ 8 ]. However, additional retrospective and prospective studies are needed to determine whether acute CMV infection is a reversible risk factor for acute VTE and can be used to change CMV screening, primary prophylaxis, and VTE treatment practices.…”

“…CMV was first described in association with venous thromboembolism in 1984. Since that time, dozens of cases of CMV-associated VTE in both immunocompromised and immunocompetent hosts have been described [ 8 ].…”

Cytomegalovirus-associated Venous and Arterial Thrombotic Disease

“…14 We suspect that CMV-associated VTE is likely underrecognized because CMV testing is not routinely performed outside of immunocompromised populations. 15 However, additional retrospective and prospective studies are needed to determine whether acute CMV infection is a reversible risk factor for acute VTE and can be used to change CMV screening, primary prophylaxis, and VTE treatment practices.…”

Current knowledge in pathophysiology and management of Budd-Chiari syndrome and non-cirrhotic non-tumoral splanchnic vein thrombosis

“…56,57 Acute cytomegalovirus infection Acute cytomegalovirus (CMV) infection is a cause of NCPVT. 58 Several explanations have been put forward. One plausible mechanism of CMVinduced thrombosis involves formation of antiphospholipid syndrome antibodies observed in patients in response to CMV infection, 59 resulting in a transient hypercoagulable state.…”

“…Translation to humans was postulated by formation of anti-b2GPI antibodies against TIFI which would bind endogenous human b2GPI on the surface of endothelial cells, leading to activation of the coagulation cascade. 58,60 The composition of the CMV envelope might also contribute to thrombosis. Indeed, the CMV surface contains the necessary procoagulant phospholipid for assembly of coagulation cascade proteins, thus favouring coagulation activation.…”