Document Detail


Bioactivity of enoxaparin in critically ill patients with normal renal function.
MedLine Citation:
PMID:  23227470     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 TGARC-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.
AIM: 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.
METHODS: 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 of40 mg enoxaparin. The thrombus size of a clot formed in an ex vivo perfusion chamber and endogenous thrombin potential (ETP) were measured.
RESULTS: 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 [IQR0.59-2.1] 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 pre-dose (P = 0.029) and was not different between the groups.
CONCLUSION: 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.
Authors:
Ghazaleh Gouya; Stefan Palkovits; Stylianos Kapiotis; Christian Madl; Gottfried Locker; Alexander Stella; Michael Wolzt; Gottfried Heinz
Publication Detail:
Type:  Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  74     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-12-05     Completed Date:  2013-03-06     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  806-14     Citation Subset:  IM    
Affiliation:
Department of Clinical Pharmacology, Medical University Vienna, Währinger Gürtel 18-20, Vienna, Austria. ghazaleh.gouya@meduniwien.ac.at
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Anticoagulants / pharmacokinetics,  pharmacology*
Case-Control Studies
Critical Illness
Enoxaparin / pharmacokinetics,  pharmacology*
Factor Xa / antagonists & inhibitors*
Female
Humans
Injections, Subcutaneous
Intensive Care Units
Kidney Function Tests
Male
Middle Aged
Models, Biological
Prospective Studies
Thrombin / drug effects,  metabolism
Thrombosis / drug therapy
Time Factors
Venous Thromboembolism / prevention & control*
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/Enoxaparin; EC 3.4.21.5/Thrombin; EC 3.4.21.6/Factor Xa
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