The right time to measure anti-Xa activity in critical illness: pharmacokinetics of therapeutic dose nadroparin

Jelmer G Sytema; Bert G Loef; Harriët M Loovers; Marijn Boer; Daniël J Touw; Marinus van Hulst

doi:10.1016/j.rpth.2023.100185

The right time to measure anti-Xa activity in critical illness: pharmacokinetics of therapeutic dose nadroparin

Res Pract Thromb Haemost. 2023 May 20;7(4):100185. doi: 10.1016/j.rpth.2023.100185. eCollection 2023 May.

Authors

Jelmer G Sytema^{1

2}, Bert G Loef³, Harriët M Loovers⁴, Marijn Boer³, Daniël J Touw⁵, Marinus van Hulst^{1

6}

Affiliations

¹ Department of Clinical Pharmacy, Martini Hospital, Groningen, the Netherlands.
² Department of Clinical Pharmacy, Hospital Nij Smellinghe, Drachten, the Netherlands.
³ Intensive Care Unit, Martini Hospital, Groningen, the Netherlands.
⁴ Department of Clinical Chemistry, Certe, Groningen, The Netherlands.
⁵ Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
⁶ Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Abstract

Background: Peak anti-Xa activity of low-molecular-weight heparin nadroparin is measured 3 to 5 hours after subcutaneous injection. In critically ill patients, physiological changes and medical therapies may result in peak activities before or after this interval, possibly impacting dosing.

Objectives: The primary objective was to determine the percentage of critically ill patients with adequately estimated peak activities drawn 3 to 5 hours after subcutaneous administration of a therapeutic dose of nadroparin. Adequate was defined as a peak activity of ≥80% of the actual peak anti-Xa activity. If ≥80% of patients had adequately estimated peak activities in the 3- to 5-hour interval, measurement in this interval was regarded as acceptable. The secondary objective was to determine the pharmacokinetic profile of nadroparin.

Methods: In this single-center, prospective study, we evaluated anti-Xa activities in patients admitted to a general intensive care unit. After ≥4 equal doses of nadroparin, anti-Xa activity was measured according to a 12- to 24-hour sampling scheme.

Results: In 25 patients, anti-Xa activities drawn between 3 and 5 hours after administration ranged 80% to 100% of the actual peak activity. Compared to the threshold level of an adequate estimation in at least 20 patients (≥80%), measuring anti-Xa activities in the 3- to 5-hour interval is an acceptable method (1-tailed binomial test; P < .02). We found a large interindividual variability for nadroparin exposure (mean ± SD area-under-the-curve_0-12h, 10.3 ± 4.8 IU·h/mL) and delayed elimination (t_1/2 range, 4.0-120.9 hours) despite adequate renal function.

Conclusion: In critically ill patients, measuring anti-Xa activity in a 3- to 5-hour interval after subcutaneous injection of therapeutic nadroparin is an acceptable method to estimate the actual peak anti-Xa activity.

Keywords: LMWH; anti-Xa; critical illness; low-molecular-weight heparin; nadroparin; pharmacokinetics.