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

• Published in: Research and practice in thrombosis and haemostasis Vol. 7; no. 4; p. 100185
• Main Authors: Sytema, Jelmer G., Loef, Bert G., Loovers, Harriët M., Boer, Marijn, Touw, Daniël J., van Hulst, Marinus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2023; Elsevier
• Subjects: anti-Xa; critical illness; LMWH; low-molecular-weight heparin; nadroparin; Original Research; pharmacokinetics; anti-Xa; pharmacokinetics; LMWH; nadroparin; low-molecular-weight heparin; critical illness
• ISSN: 2475-0379; 2475-0379
• DOI: 10.1016/j.rpth.2023.100185

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. 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. 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. 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-curve0-12h, 10.3 ± 4.8 IU·h/mL) and delayed elimination (t1/2 range, 4.0-120.9 hours) despite adequate renal function. 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. •In critically ill patients, measuring peak anti-Xa levels 3 to 5 hours after nadroparin injection may not be valid.•After ≥4 doses of nadroparin, anti-Xa was measured using a 12- to 24-hour sampling scheme.•Measuring anti-Xa levels 3 to 5 hours after injection is acceptable to estimate the peak anti-Xa levels.•Ultralong elimination half-lives up to 121 hours and 6-fold variation in exposure were found.