Subtherapeutic Anti-Xa Activity is Related to Thrombosis in Severe COVID-19

Background and purpose: Thrombosis is common in severe COVID-19. Limited evidence exists to guide anticoagulation and it’s known that conventional dosing could be subtherapeutic. We aimed to anlayze the relation between subtherapeutic anti-Xa activity and the diagnose of new thomboembolic events (TE) in severe COVID-19 patients.Methods: Observational prospective longitudinal cohort study of severe COVID-19 patients admitted into a tertiary ICU (February - November 2021). Enoxaparin was used for prophylactic and therapeutic anticoagulation. Enoxaparin dosing and dose adjustment were based on anti-Xa activity according to the hospital protocol. Screening for new TE was performed periodically according to the study design. Logistic regression was used to identify independent risk factors predicting new TE.Results: Data were available for 896 serum anti-Xa measurements from 228 subjects. Patients were 62 (95% CI; 59-63) years old and 71.9% were male. Most patients needed invasive mechanical ventilation (87.7%) and mortality was high (24.1%). A total of 28.9% new TE were diagnosed. There were 27.1% subtherapeutic anti-Xa measesurements. When multivariable logistic regression analysis was performed subtherapeutic anti-Xa activity [relative risk (RR), 4.2; p=0.000], C-reactive protein (25 mg/L increase) (RR, 1.14; p=0.005) and D-Dimer (1000 ng/L increase) (RR, 1.06; p=0.002) were the independent factors related to new TE in severe COVID-19.Conclusions: Subtherapeutic anti-Xa activity, C-reactive protein and D-Dimer were the most important factors related to TE in severe COVID-19. Anti-Xa monitoring may decrease TE in severe COVID-19. Purposely designed clinical trials should be carried out to confirm this benefit.