Optimising the Nadroparin Dose for Thromboprophylaxis During Hemodialysis by Developing a Population Pharmacodynamic Model Using Anti-Xa Levels

• Published in: Clinical pharmacokinetics Vol. 61; no. 11; pp. 1559 - 1569
• Main Authors: Jaspers, Tessa C. C., Meijer, Charlotte E., Vleming, Louis Jean, Franssen, Casper F. M., Diepstraten, Jeroen, Lukens, Michael V., van den Bemt, Patricia M. L. A., Maat, Barbara, Khorsand, Nakisa, Touw, Daniël J., Koomen, Jeroen V.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.11.2022; Springer Nature B.V
• Subjects: Administration, Intravenous; Anticoagulants; Anticoagulants - pharmacology; Blood clots; Clinical medicine; Datasets; Dialysate; Dialyzers; Factor Xa Inhibitors - therapeutic use; Hemodialysis; Humans; Internal Medicine; Laboratories; Medical ethics; Medicine; Medicine & Public Health; Nadroparin - pharmacology; Nadroparin - therapeutic use; Original; Original Research Article; Patients; Pharmacodynamics; Pharmacology/Toxicology; Pharmacotherapy; Renal Dialysis; Software; Venous Thromboembolism - drug therapy; Venous Thromboembolism - etiology; Venous Thromboembolism - prevention & control; Netherlands; Germany
• ISSN: 0312-5963; 1179-1926; 1179-1926
• DOI: 10.1007/s40262-022-01162-x

Introduction The optimal nadroparin dose in patients undergoing hemodialysis is difficult to determine in clinical practice. Anti-Xa levels ≥ 0.4 IU/mL and < 2.0 IU/mL are suggested to prevent thrombus formation within the extracorporeal circuit whilst minimizing bleeding risk. We aimed to characterize the variability in the association between dose and anti-Xa levels, identify patient and dialysis characteristics that explained this variability, and optimize nadroparin dosing based on the identified characteristics. Methods Anti-Xa samples were collected in patients who received intravenous nadroparin as thromboprophylaxis during routine dialysis sessions. A population pharmacodynamic model was developed using non-linear mixed-effects modelling. The percentage of patients ≥ 0.4 IU/mL (efficacy) and < 2.0 IU/mL (safety) was simulated for different doses, patient and dialysis characteristics. Results Patients ( n = 137) were predominantly receiving standard hemodialysis (84.7% vs. hemodiafiltration 15.3%) and had a mean bodyweight of 76.3 kg (± 16.9). Lean body mass (LBM), mode of dialysis, and dialyzer partially explained between-subject variability in anti-Xa levels. Patients on hemodiafiltration and those receiving hemodialysis with a high LBM (≥ 80 kg) had a low probability (< 29%) of anti-Xa levels ≥ 0.4 IU/mL during the entire dialysis session. All patients, except hemodialysis patients with a low LBM (< 50 kg), had a high probability (> 70%) of peak anti-Xa levels < 2.0 IU/mL. Conclusion Mainly patients receiving hemodiafiltration and those receiving hemodialysis with a high LBM can benefit from a higher nadroparin dose than currently used in clinical practice, while having anti-Xa levels < 2.0 IU/mL.