• anti-FXa activity;
  • critically ill;
  • enoxaparin;
  • ex vivo thrombosis model;
  • thrombin generation


• 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.


• 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.