CMV Exposure at Transplantation Is an Independent Predictor of Thrombotic Events

Donor cytomegalovirus (CMV) seropositivity at transplantation was associated with increased risk for thrombotic events post-transplantation, according to study results published in Clinical Infectious Diseases.  

Previously, literature has demonstrated an association between CMV and atherosclerosis and increased mortality risk among patients who have not required transplantation. This association has been found in patients with remote CMV infection and no indications of active replication. Acute CMV infection can also result in a hypercoagulable state, and many venous thrombotic events reported in association with acute CMV have been seen in immunocompetent patients. Therefore, researchers aimed to assess the effect of CMV exposure at transplantation on the rate of post-transplant thrombotic events, among patients who have never had CMV.

In a retrospective cohort study, researchers used data from patients at the University of Alberta Hospital in Canada between July 2005 and January 2018. Solid organ transplantat recipients who were CMV-seronegative at transplantation and received an allograft from either CMV-seropositive or CMV-seronegative donors and with follow-up data available for a minimum of 1-year post-transplantation were included in the study. All recipients who received a transplant from a CMV-seropositive donor received universal antiviral prophylaxis with ganciclovir and/or valganciclovir. A CMV viral load <500 copies/mL was considered negative.

Researchers recorded all thrombotic events that occurred at any point in time and assessed the incidence of thrombotic events 5 years after solid organ transplantation.

Of the 392 patients who received a solid organ transplant (mean age, 47 years; 76% men), 181 (46%) received transplantation from a CMV-seropositive donor: 151 a liver transplant, 188 a kidney transplant, 45 a pancreas transplant, and 8 received other transplants.

Compared with recipients of a transplant from a CMV-seronegative donor, recipients of a transplant from a CMV-seropositive donor were slightly older (51 vs 48 years; P =.032) but other variables, including cardiovascular risk factors and pre-transplant thrombotic events, did not differ between the groups.

At 5-year follow-up, the incidence of thrombotic events was higher among patients who received a transplant from a CMV-seropositive donor (19% vs 10%; P =.008). When researchers assessed the specific type of thrombotic event, pulmonary embolism occurred in 4% of recipients from the CMV-seropositive donor group vs less than 1% from the CMV-seronegative donor group.

Of the 35 patients who received a CMV-seropositive transplant and experienced thrombotic events, 19 had CMV infection, and in 11 of these cases CMV infection preceded the occurrence of thrombotic events. Conversely, in the CMV-seronegative donor recipients, no cases of CMV infection resulted in thrombotic events. Results also demonstrated that male sex was a protective variable for the development of a post-transplant thrombotic event.

After adjusting for potential confounders, transplantation from a CMV-seropositive donor was independently associated with an increased risk for thrombotic events over 5 years (adjusted hazard ratio, 3.027; 95% CI 1.669-5.488; P <.001).

Findings from this study “suggests that CMV exposure could participate in the occurrence of [thrombotic events] via a different pathophysiologic mechanism, independent of the CMV infection pathway, and that having better cellular-mediated immunity to CMV may result in endothelial dysfunction as a result of increased cytokine release and immune inflation,” noted the researchers. They added, “Whether CMV infection is a surrogate marker of less immune inflation should be investigated in further studies.”

Disclosure: Juan G. Abraldes, MD, and Carlos Cervera, MD, PhD, declared affiliations with the pharmaceutical industry. Please see the original reference for their disclosures.

Reference

Belga S, MacDonald C, Chiang D, et al. Donor graft CMV-serostatus and the risk of arterial and venous thrombotic events in seronegative recipients after non-thoracic solid organ transplantation [published online February 6, 2020]. Clin Infect Dis. doi:10.1093/cid/ciaa125