Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry
Comparison study 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.
Summary
Compares aPTT vs rotational thromboelastometry (ROTEM) for monitoring leech-derived lepirudin and synthetic argatroban in ICU. ROTEM provides more reliable detection of hypocoagulation.
Why This Matters for Hirudotherapy
This sub-study of the double-blind randomized "ALicia" trial examined whether rotational thromboelastometry (ROTEM) parameters or global clotting times (e.g., thrombin time) might better reflect plasma concentrations of argatroban and lepirudin than aPTT in 35 critically ill patients requiring anticoagulation for heparin-induced thrombocytopenia. Lepirudin is a recombinant derivative of hirudin, the signature anticoagulant of the medicinal leech, so evidence on how its anticoagulant intensity is best monitored is directly relevant to ASH/hirudotherapy practice and to the broader clinical translation of leech-secretome-derived direct thrombin inhibitors. The authors report that TT and ROTEM parameters correlated significantly with plasma levels of both drugs, whereas aPTT did not. An honest caveat is that this was a small sub-study of critically ill patients, so the findings are exploratory rather than definitive and may not generalize to other populations.
Citation
Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry.
Beiderlinden M et al. · BMC anesthesiology, 2018
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