The Effect of Anti-coagulation Dosage on the Outcome of Hospitalized COVID-19 Patients in Ethiopia: A multi-center retrospective cohort study

Abstract Background: Studies have indicated that hospitalized COVID-19 patients benefit from anticoagulation therapy in terms of survival; however, there is an ongoing controversy over the optimum anticoagulant dosage. This study aimed to compare clinical outcomes between patients who received prophylactic anticoagulation and those who received therapeutic anticoagulation. Methods: A multi-center retrospective cohort study was conducted to determine the impact of anticoagulation dosage in hospitalized COVID-19 patients in Ethiopia. The primary outcome measure was in-hospital mortality, and it was assessed using multivariable binary logistic regression and covariate-adjusted Cox Proportional Hazard model. For critical and severe COVID-19 patients, subgroup analyses were performed using multivariable binary logistic regression model and multivariable Cox regression models. Result: A total of 472 hospitalized COVID-19 patients were included in this study, of whom 235 (49.8%) received therapeutic anticoagulation and 237 (50.2%) received prophylactic dose. The demographic and baseline clinical characteristics were roughly similar between the groups. After adjustment for several confounders, in critical COVID-19 subgroup, therapeutic dose of anticoagulation was significantly associated with a higher inpatient mortality (AOR 2.27, 95% CI, 1.18 - 4.35, p = 0.013), whereas in severe COVID-19 subgroup, anticoagulation dosage was not associated with inpatient mortality (OR, 1.02, 95% CI, 0.45 – 2.33, p = 0.958). In severe COVID-19 patient group however, the incidence of thrombosis was slightly lower in the therapeutic group as compared with prophylactic group although the difference was not statistically significant (AOR 0.15, 95% CI, 0.02 – 1.20, p =0.073). Although there were only six major bleeding events in this study, all these were recorded from patients in the therapeutic subgroup, making the difference statistically significant (p = 0.013). Conclusion: Our findings suggest that, in critical COVID-19 patients, when compared to prophylactic anticoagulation, therapeutic anticoagulation may offer no survival advantage, no improved protection against thrombosis and pose a higher risk of bleeding. In severe COVID-19 subgroup, therapeutic anticoagulation may prolong hospital stay and not improve survival, although it may offer a slight protection against thrombosis. These findings suggest that the benefit of therapeutic anticoagulation for hospitalized COVID-19 patients should be further studied, if possible, with a randomized control trial in this setting.