Bioactivity of enoxaparin in critically ill patients with normal renal function

Abstract

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. 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 of 40 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 [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. Conclusion Similar bioactivity was achieved with a standard dose of subcutaneous enoxaparin in this selected cohort of ICU and general ward patie...

Evaluation of unfractionated heparin versus low‐molecular‐weight heparin and fondaparinux for pharmacologic venous thromboembolic prophylaxis in critically ill patients with cancer

“…Our study reinforces the findings from a variety of clinical settings that LMWH prophylaxis reduces the proportion of patients with a significant bleeding event when compared with UFH and has a reduced rate of HIT . The significant reduction in bleeding may be because of the more consistent pharmacokinetic and dynamic properties demonstrated by LMWHs when compared with UFH . Our secondary analysis showed approximately a 2% significant reduction in significant bleeding in the metastatic and non‐metastatic disease subgroups, but no significant difference was seen in the lymphoma subgroup.…”

Plasma anti-FXa level as a surrogate marker of the adequacy of thromboprophylaxis in critically ill patients: A systematic review

“…Trial characteristics are presented in Table 1. Most of these studies (10 observational studies and two RCTs) tested the effects of different dosages of enoxaparin [15][16][17][18][19][20][21][22][23][24][25][26], whereas four observational studies assessed dalteparin [27][28][29][30], and one each tested certoparin [31] and nadroparin [32]. No studies testing tinzaparin were identified.…”

“…The quality of the studies according to the Down and Black score is shown in Table 2. The median total score (interquartile range, IQR) was 19 [15][16][17][18][19][20]…”

New oral anticoagulants and regional anaesthesia

“…heparin, 1 although the anticoagulant effect of heparin is immediate. It takes 3 h for the peak anti-factor Xa (anti-FXa) plasma activity of enoxaparin, 46 yet the ASRA recommended a 2 h interval between catheter removal and subsequent redose. These recommendations on heparin and enoxaparin have been followed in thousands of patients with no reports of spinal haematoma, although this might represent underreporting and not proof of safety of the guidelines.…”