Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry — ALicia substudy
Randomized double-blind clinical trial published in BMC Anesthesiology (2018)
Abstract
BACKGROUND: Argatroban or lepirudin anticoagulation therapy in patients with heparin induced thrombocytopenia (HIT) or HIT suspect is typically monitored using the activated partial thromboplastin time (aPTT). Although aPTT correlates well with plasma levels of argatroban and lepirudin in healthy volunteers, it might not be the method of choice in critically ill patients. However, in-vivo data is lacking for this patient population. Therefore, we studied in vivo whether ROTEM or global clotting times would provide an alternative for monitoring the anticoagulant intensity effects in critically ill patients. METHODS: This study was part of the double-blind randomized trial "Argatroban versus Lepirudin in critically ill patients (ALicia)", which compared critically ill patients treated with argatroban or lepirudin. Following institutional review board approval and written informed consent, for this sub-study blood of 35 critically ill patients was analysed. Before as well as 12, 24, 48 and 72 h after initiation of argatroban or lepirudin infusion, blood was analysed for aPTT, aPTT ratios, thrombin time (TT), INTEM CT,INTEM CT ratios, EXTEM CT, EXTEM CT ratios and maximum clot firmness (MCF) and correlated with the corresponding plasma concentrations of the direct thrombin inhibitor. RESULTS: To reach a target aPTT of 1.5 to 2 times baseline, median [IQR] plasma concentrations of 0.35 [0.01-1.2] μg/ml argatroban and 0.17 [0.1-0.32] μg/ml lepirudin were required. For both drugs, there was no significant correlation between aPTT and aPTT ratios and plasma concentrations. INTEM CT, INTEM CT ratios, EXTEM CT, EXTEM CT ratios, TT and TT ratios correlated significantly with plasma concentrations of both drugs. Additionally, agreement between argatroban plasma levels and EXTEM CT and EXTEM CT ratios were superior to agreement between argatroban plasma levels and aPTT in the Bland Altman analysis. MCF remained unchanged during therapy with both drugs. CONCLUSION: In critically ill patients, TT and ROTEM parameters may provide better correlation to argatroban and lepirudin plasma concentrations than aPTT. TRIAL REGISTRATION: ClinicalTrials.gov , NCT00798525 , registered on 25 Nov 2008.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Sub-study of the ALicia RCT in 35 critically ill HIT-suspect patients found rotational thromboelastometry (ROTEM CT) and thrombin time correlate better with argatroban/lepirudin plasma concentrations than the conventional aPTT, which performed poorly in this population.
Por qué esto importa para la hirudoterapia
This substudy of the double-blind randomized ALicia trial analyzed blood from 35 critically ill patients receiving argatroban or lepirudin for suspected heparin-induced thrombocytopenia, comparing aPTT, thrombin time, and ROTEM parameters against plasma drug concentrations. The key finding was that aPTT did not correlate significantly with plasma concentrations of either drug, whereas thrombin time and ROTEM parameters (INTEM CT, EXTEM CT) showed significant correlations, suggesting these may provide better monitoring in critically ill patients. The abstract does not describe lepirudin's relationship to hirudin or mention leeches. For ASH, the connection to hirudotherapy is not established by the abstract; the study discusses lepirudin purely as a direct thrombin inhibitor in a modestly sized substudy population.
Citación
Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry - a prospectively controlled randomized double-blind clinical trial.
Beiderlinden M et al. · BMC Anesthesiology, 2018
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: June 18, 2026