Pharmacokinetic dynamic relationships
Bioactivity of enoxaparin in critically ill patients with normal renal function
Article first published online: 9 OCT 2012
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 74, Issue 5, pages 806–814, November 2012
How to Cite
Gouya, G., Palkovits, S., Kapiotis, S., Madl, C., Locker, G., Stella, A., Wolzt, M. and Heinz, G. (2012), Bioactivity of enoxaparin in critically ill patients with normal renal function. British Journal of Clinical Pharmacology, 74: 806–814. doi: 10.1111/j.1365-2125.2012.04285.x
- Issue published online: 9 OCT 2012
- Article first published online: 9 OCT 2012
- Accepted manuscript online: 30 MAR 2012 07:01AM EST
- Received; 20 October 2011; Accepted; 23 March 2012; Accepted Article Published Online; 30 April 2012
- anti-FXa activity;
- critically ill;
- ex vivo thrombosis model;
- thrombin generation
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Venous thromboembolism is a frequent complication in critically ill patients that has a negative impact on patient outcomes.
• Critically ill patients have significantly lower plasma anti-factor-Xa activity levels compared with control patients after administration of subcutaneous heparin.
• The clinical relevance of the different anti-factor-Xa levels after prophylactic doses of low molecular weight heparin (LMWH) in critically ill patients is not completely understood.
WHAT THIS STUDY ADDS
• The standard dose of 40 mg enoxaparin led to a significant increase in anti-FXa levels in this selected cohort of ICU patients with normal renal function.
• This study found only subtle pharmacokinetic differences, but a comparable pharmacodynamic action, after enoxaparin administration in critically ill and normal medical ward patients.
• Thrombin generation with TGA RC-low and TGA RC-high reagents was significantly reduced in ICU and normal ward patients after receiving LMWH. Both readouts appear equally useful for estimating the pharmacodynamics of enoxaparin.
• The ex vivo model of thrombosis was used for the first time in patients to evaluate the anti-thrombotic activity of LMWH. This method did not show any difference in thrombus formation after administration of enoxaparin in the individual group of patients.
In critically ill patients, reduced anti-FXa plasma activity following subcutaneous administration of enoxaparin or nadroparin has been described. In this study, we aimed to investigate the bioactivity of enoxaparin in critically ill patients and controls.
A prospective, controlled, open label study was performed on a medical intensive care unit (ICU) and a general medical ward. Fifteen ICU patients (male = 12, median age 52 years [IQR 40−65], with a median Simplified Acute Physiology Score of 30 [IQR 18−52]) and sex- and age-matched medical ward patients were included. The anti-FXa plasma activity was measured after a single subcutaneous dose of 40 mg enoxaparin. The thrombus size of a clot formed in an ex vivo perfusion chamber and endogenous thrombin potential (ETP) were measured.
The anti-FXa plasma activity increased significantly after enoxaparin administration, with peak levels at 3 h after treatment, but was comparable between the ICU and medical ward groups (median 0.16 IU ml−1[IQR 0−0.22 IU ml−1]vs. 0.2 IU ml−1[IQR 0.15−0.27 IU ml−1], respectively, P= 0.13). The area under the anti-FXa activity curve from 0–12 h was similar between the groups (median 0.97 IU ml−1 h [IQR 0.59−2.1] and 1.48 IU ml−1 h1[IQR 0.83−1.62], P= 0.42 for the ICU group compared with the control group, respectively). The ETP was lower in the ICU group (P < 0.05) at baseline, but it was comparable at 3 h between the groups. Thrombus size decreased at 3 h compared with predose (P= 0.029) and was not different between the groups.
Similar bioactivity was achieved with a standard dose of subcutaneous enoxaparin in this selected cohort of ICU and general ward patients with normal renal function.