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

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	100185
Number of pages	9
Journal	Research and practice in thrombosis and haemostasis
Volume	7
Issue number	4
DOIs	https://doi.org/10.1016/j.rpth.2023.100185
Publication status	Published - May-2023

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@article{cc8238137ff54481b8f44ff55c672cb7,

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

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.",

author = "Sytema, {Jelmer G} and Loef, {Bert G} and Loovers, {Harri{\"e}t M} and Marijn Boer and Touw, {Dani{\"e}l J} and {van Hulst}, Marinus",

note = "{\textcopyright} 2023 The Authors.",

year = "2023",

month = may,

doi = "10.1016/j.rpth.2023.100185",

language = "English",

volume = "7",

journal = "Research and practice in thrombosis and haemostasis",

issn = "2475-0379",

publisher = "Wiley",

number = "4",

}

TY - JOUR

T1 - The right time to measure anti-Xa activity in critical illness

T2 - pharmacokinetics of therapeutic dose nadroparin

AU - Sytema, Jelmer G

AU - Loef, Bert G

AU - Loovers, Harriët M

AU - Boer, Marijn

AU - Touw, Daniël J

AU - van Hulst, Marinus

PY - 2023/5

Y1 - 2023/5

N2 - 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.

AB - 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.

U2 - 10.1016/j.rpth.2023.100185

DO - 10.1016/j.rpth.2023.100185

M3 - Article

C2 - 37449055

SN - 2475-0379

VL - 7

JO - Research and practice in thrombosis and haemostasis

JF - Research and practice in thrombosis and haemostasis

IS - 4

M1 - 100185

ER -

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

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