COVID-19 outcomes in persons with hemophilia: results from a US-based national COVID-19 surveillance registry

INTRODUCTION: Hypercoagulable state contributing to thrombotic complications worsens COVID-19 severity and outcomes, while anticoagulation improves outcomes by alleviating hypercoagulability. OBJECTIVES: Examine whether hemophilia, an inherent hypocoagulable condition, offers protection against COVID-19 severity and reduces VTE risk in persons with hemophilia (PwH). PATIENTS/METHODS: A 1: 3 propensity score (PS) matched retrospective cohort study used national COVID-19 registry data (January 2020 through January 2022) to compare outcomes between 300 male PwH and 900 matched controls without hemophilia. RESULTS: Analyses of PwH demonstrated known risk-factors (older age, heart failure, hypertension, cancer/malignancy, dementia, renal and liver disease) contributed to severe COVID-19 and/or 30-day-all-cause mortality. Non-CNS bleeding was an additional risk-factor for poor outcomes in PwH. Odds of developing VTE with COVID-19 in PwH were associated with pre-COVID VTE diagnosis (OR 51.9, 95% CI 12.8-266, p<0.001), anticoagulation therapy (OR 12.7, 95% CI 3.01-48.6, p<0.001) and pulmonary disease (OR 16.1, 95% CI 10.4-25.4, p<0.001). Thirty-day-all-cause-mortality (OR 1.27, 95% CI 0.75-2.11, p=0.3), and VTE events (OR 1.32, 95% CI 0.64-2.73, p=0.4) were not significantly different between matched cohorts; however, hospitalizations (OR 1.58, 95% CI 1.20-2.10, p 0.001) and non-CNS bleeding events (OR 4.78, 95% CI 2.98-7.48, p<0.001) were increased in PwH. In multivariate analyses, hemophilia did not reduce adverse outcomes (OR 1.32, 95% CI 0.74-2.31, p 0.2) nor VTE (OR 1.14; 95% CI 0.44-2.67, p 0.8) but increased bleeding risk (OR 4.70, 95% CI 2.98-7.48, p<0.001). CONCLUSION: After adjusting for patient characteristics/comorbidities, hemophilia increased bleeding risk with COVID-19 but did not protect against severe disease and VTE.