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

Tessa C C Jaspers*, Charlotte E Meijer, Louis Jean Vleming, Casper F M Franssen, Jeroen Diepstraten, Michael V Lukens, Patricia M L A van den Bemt, Barbara Maat, Nakisa Khorsand, Daniël J Touw, Jeroen V Koomen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)1559–1569
Number of pages11
JournalClinical Pharmacokinetics
Early online date30-Aug-2022
Publication statusPublished - Nov-2022

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