Does the elevated thrombosis risk of males relative to females help account for the excess male mortality observed in Covid-19? An observational study

Cohen, K. R.; Anderson, D.; Ren, S.; Cook, D. J.

Objectives: We sought to determine whether underlying thrombophilia helps account for excess Covid-19 mortality rates in males relative to females. Specifically, we asked: What is the contribution of thrombophilia to the excess Covid-19 mortality risk among males? Design: Cross-sectional observational study. Setting: Data were sourced from electronic medical records (EMRs) drawn from over 200 US hospital systems. Participants: 16,576 patients hospitalized with Covid-19, aged 40 and above. Main outcome measures: The primary study outcome was Covid-19 mortality. We measured: 1) the mortality rate of male patients relative to female patients, 2) the rate of thrombotic diagnoses occurring during hospitalization for Covid-19 in male and female patients, and 3) the mortality rate when evidence of thrombosis was present. We used hospital EMR data to determine the rates of a thrombotic diagnosis by sex, and D-dimer levels to help identify undiagnosed thrombosis. Results: The Covid-19 mortality rate of males was higher than that of females by 16.1%. Males with Covid-19 also had a 25.4% higher rate of receiving a thrombotic diagnosis compared to females with Covid-19. The mortality rate of all patients with a thrombotic diagnosis was 42.4%, a rate over twice that of Covid-19 patients without a thrombotic diagnosis (adjusted OR 2.4 (2.17 to 2.65), p-value < .001). When defining thrombosis as either a documented thrombotic diagnosis or markedly elevated D-dimer levels, over half of the excess mortality in male patients could be explained by thrombophilia. Conclusions: Our findings suggest the higher Covid-19 mortality rate in males may be significantly accounted for by the increased propensity for thrombophilia among males. This thrombotic tendency is additive to the thrombotic risk associated with Covid-19. Understanding the mechanisms that underlie male thrombophilia may allow for the advancement of effective anticoagulation strategies that reduce Covid-19 mortality.