Anticoagulation Monitoring with Activated Partial ThromboPlastin Time and Anti-Xa Activity in Intensive Care Unit Patients: Interest of Thrombin Generation Assay

• Published in: International journal of molecular sciences Vol. 23; no. 19; p. 11219
• Main Authors: Billoir, Paul, Elie, Thomas, Levy, Jerrold H, Besnier, Emmanuel, Dureuil, Bertrand, Veber, Benoit, Le Cam-Duchez, Véronique, Clavier, Thomas
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.09.2022; MDPI
• Subjects: activated partial thromboplastin time; Adult; Anticoagulants - pharmacology; Anticoagulants - therapeutic use; Biomarkers; C-Reactive Protein; Coagulation; coagulation tests; Drug Monitoring; Evaluation; factor Xa; Factor Xa Inhibitors - pharmacology; Factor Xa Inhibitors - therapeutic use; Heparin; Heparin - pharmacology; Heparin, Low-Molecular-Weight; Humans; Inflammation; Inflammatory response; Intensive care; intensive care unit; Intensive Care Units; Monitoring; Partial Thromboplastin Time; Patients; Plasma; Population; Prospective Studies; Surgery; Therapeutic targets; Thrombin; Thromboembolism; Thromboplastin; Trauma; heparin; activated partial thromboplastin time; inflammation; intensive care unit; factor Xa; thrombin generation; coagulation tests
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms231911219

Current guidelines recommend monitoring the anticoagulant effect of unfractionated heparin (UFH) by measuring anti-Xa activity rather than activated partial thromboplastin time (aPTT) in intensive care unit (ICU) patients. The primary objective of this study was to evaluate the correlation of aPTT, anti-Xa activity, and thrombin generation in UFH-treated ICU patients. A prospective observational pilot study was conducted in adult surgical ICU patients treated with UFH. aPTT and anti-Xa activity were monitored daily. The therapeutic target was aPTT between 50 s and 84 s, and/or anti-Xa between 0.3 and 0.7 U/mL. Correlation among aPTT, anti-Xa activity, and thrombin generation was determined by measuring endogenous thrombin potential (ETP), with the inflammatory response evaluated. C-reactive protein (CRP) was used as a marker of inflammatory response. The plasma of 107 samples from 30 ICU patients was analyzed. The correlation between aPTT and anti-Xa activity was 0.66, CI95% [0.54;0.76] (p < 0.0001). Although thrombin generation, aPTT, and anti-Xa were correlated with inflammatory responses, the correlation was higher with thrombin generation and anti-Xa activity compared to aPTT. When aPTT was in a therapeutic range, a low thrombin generation was observed but was 50% inhibited when anti-Xa was in a therapeutic range. Coagulation testing with aPTT, anti-Xa correlated with thrombin generation. A 50% decrease in thrombin generation was observed when anti-Xa was within a therapeutic range. Further work is needed to evaluate coagulation biomarker responses and clinical outcomes in specific ICU populations.