Anticoagulation, Mortality, Bleeding and Pathology Among Patients Hospitalized with COVID-19: A Single Health System Study

Nadkarni, Girish N.; Lala, Anuradha; Bagiella, Emilia; Chang, Helena L.; Moreno, Pedro; Pujadas, Elisabet; Arvind, Varun; Bose, Sonali; Charney, Alexander W.; Chen, Martin D.; Cordon-Cardo, Carlos; Dunn, Andrew S.; Farkouh, Michael E.; Glicksberg, Benjamin; Kia, Arash; Kohli-Seth, Roopa; Levin, Matthew A.; Timsina, Prem; Zhao, Shan; Fayad, Zahi A.; Fuster, Valentin

Background Thromboembolic disease is common in coronavirus disease-19 (COVID-19). There is limited evidence on association of in-hospital anticoagulation (AC) with outcomes and postmortem findings. Objective To examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies. Methods A retrospective analysis examining association of AC with mortality, intubation and major bleeding. We also conducted sub-analyses on association of therapeutic vs prophylactic AC initiated ≤48 hours from admission. We describe thromboembolic disease contextualized by pre-mortem AC among consecutive autopsies. Results Among 4,389 patients, median age was 65 years with 44% female. Compared to no AC (n=1530, 34.9%), therapeutic (n=900, 20.5%) and prophylactic AC (n=1959, 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]=0.53; 95%CI: 0.45-0.62, and aHR=0.50; 95%CI: 0.45-0.57, respectively), and intubation (aHR 0.69; 95%CI: 0.51-0.94, and aHR 0.72; 95% CI: 0.58-0.89, respectively). When initiated ≤48 hours from admission, there was no statistically significant difference between therapeutic (n=766) vs. prophylactic AC (n=1860) (aHR 0.86, 95%CI: 0.73-1.02; p=0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27/900 (3.0%) on therapeutic, 33/1959 (1.7%) on prophylactic, and 29/1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3/11 (27%) were on therapeutic AC. Conclusions AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared to prophylactic AC, therapeutic AC was associated with lower mortality, though not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.