A retrospective safety study evaluating differences of safety and outcomes of prophylactic versus therapeutic doses of enoxaparin in patients admitted to Charlotte Maxeke Johannesburg Academic Hospital with confirmed COVID-19 pneumonia presenting with disease of mild to moderate severity

Abstract

Background: Coagulopathy is a common finding in coronavirus disease 2019 (COVID-19) infection and contributes towards disease severity and mortality. International treatment protocols advocate for the early use of anticoagulation therapy for patients admitted with COVID-19 pneumonia. Objectives: In patients admitted with COVID-19 infection, this study served as a safety study to identify any increased risk of major bleeding in those treated with therapeutic doses (1mg/kg/twice daily subcutaneously) of a low-molecular weight heparin (LWMH, i.e. enoxaparin) compared to those treated with prophylactic doses (0.5mg/kg/daily subcutaneously). In addition, it sought to identify differences in outcomes (other than bleeding) when comparing different enoxaparin doses in patients hospitalised with COVID-19 infection. Methods and findings: This retrospective study included 100 patients (over the age of 18 years) who were admitted to Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) with confirmed COVID-19 pneumonia of mild to moderate severity between 01 March 2020 and 31 August 2020. Data was captured using the Research Electronic Data Capture (REDCap) database and National Health Laboratory Services (NHLS)-Labtrak. The following outcomes were measured: recovery, progression to invasive ventilation, death, and bleeding. Of the patients included in this study, 40 were treated with prophylactic doses of enoxaparin and 60 were treated with therapeutic doses. Outcomes were as follows: 81% recovered, 20% progressed to invasive ventilation, and 19% demised. No patients experienced episodes of bleeding during their admission. Of the recovery group, 42% (n=34) of patients received prophylactic doses of enoxaparin, and 58% (n=47) received therapeutic doses. V With regards to patients who progressed to requiring invasive ventilation and admission to the intensive care unit (ICU), prophylactic enoxaparin doses were administered in 4 patients and 16 patients received therapeutic doses. Of the patients who demised, 32% (n=6) had been treated with prophylactic enoxaparin doses and 68% (n=13) were treated with therapeutic doses. Prophylactic enoxaparin was associated with a higher rate of recovery (p-value = 0.001) but also with progression of disease (p-value = 0.0495). Death was approximately twice more common in those treated with therapeutic enoxaparin. Conclusion: The findings of this study revealed no increased risk of bleeding when using therapeutic doses of enoxaparin as compared to prophylactic doses in the treatment of non-severe COVID-19. Current literature shows that once COVID-19 patients progress to severe disease, use of therapeutic anticoagulation results in a higher risk of bleeding. Our study did not demonstrate such risks. In addition, our study showed that use of prophylactic enoxaparin was associated with increased survival rates when compared to therapeutic doses. This contrasts to existing literature. We recognise the limitations of a small sample size and a unicentric population.