Trough anti-Xa activity after intermediate dose nadroparin for thrombosis prophylaxis in critically ill patients with COVID-19 and acute kidney injury.

Our objective was to assess the incidence of drug bioaccumulation in critically ill COVID-19 patients with AKI receiving intermediate dose nadroparin for thrombosis prophylaxis. We conducted a Prospective cohort study of critically ill COVID-19 patients. In patients on intermediate dose nadroparin (5700 IU once daily) we assessed the incidence of bioaccumulation (trough anti-Xa level > 0.2 IU/mL) stratified according to presence of AKI. We quantified this association using multilevel analyses. To assess robustness of our observations, we explored the association between AKI and anti-Xa activity in patients receiving high dose nadroparin (> 5700 IU). 108 patients received intermediate dose nadroparin, of whom 24 had AKI during 36 anti-Xa measurements. One patient with AKI (4.2% [95%CI 0.1-21%]) and 1 without (1.2% [95%CI 0.03-6.5%]) developed bioaccumulation (p = 0.39). Development of AKI was associated with a mean increase of 0.04 (95%CI 0.02-0.05) IU/ml anti-Xa activity. There was no statistically significant association between anti-Xa activity and AKI in 51 patients on high dose nadroparin. There were four major bleeding events, all in patients on high dose nadroparin. In conclusion, Bioaccumulation of an intermediate dose nadroparin did not occur to a significant extent in critically ill patients with COVID-19 complicated by AKI. Dose adjustment in AKI may be unnecessary.

Anti-factor xa activity after intermediate dose nadroparin for thrombosis prophylaxis in critically ill COVID-19 patientswith and without acute kidney injury

Background : The optimal prophylaxis for prevention of venous thromboembolism (VTE) in critically ill COVID-19 patients with acute kidney injury (AKI) is uncertain. Low-molecular-weight heparins are mainly excreted by the kidney and AKI may predispose to bioaccumulation with increased risk of bleeding. Dose adjustment or switch to unfractionated heparin is generally recommended, based on low quality evidence. Aims : To describe trough anti-Xa activity in critically ill patients with and without AKI receiving prophylaxis with intermediate dose nadroparin. Methods : This was a prospective cohort study including critically ill COVID-19 patients receiving intermediate dose nadroparin (5700 IU once daily). Trough anti-Xa levels were measured twice weekly 20-25 h after the previous dose. AKI was defined according to guideline criteria using serum creatinine and renal replacement therapy. The main outcome was the proportion of patients with bioaccumulation, defined as a trough anti-Xa level >0.2 IU/mL at any time, in which case the dose had to be reduced. In patients with AKI and repeated measurements we calculated the range of trough anti-Xa values as a proxy for within-patient variation. Results : There were 234 trough anti-Xa measurements in 108 patients. In twenty-four patients 36 measurements were made during AKI. Two patients had evidence of bioaccumulation on a single measurement, 1 with and 1 without AKI (Figure 1). In 20 patients who had AKI and repeated measurements, the median range of anti-Xa values was 0.05 IU/mL (IQR < 0.04 IU/mL -0.08 IU/mL;lowest range <0.04 IU/mL;highest range 0.20 IU/mL, Figure 2). Four patients had major bleeding events during hospital stay (2.4%;95%CI 0.04%-8.9%) but none while on intermediate dose nadroparin. Conclusions : Bioaccumulation was rare in critically ill patients with AKI who received intermediate dose nadroparin for thrombosis prophylaxis. These data suggest there is no need for dose adjustment nor monitoring of nadroparin prophylaxis in patients with COVID-19 and AKI. The selected population may limit generalization to other patients.