Summary
Purpose
Adequate monitoring of the effect of the direct thrombin inhibitor argatroban may facilitate individualized dosing and perioperative management of anticoagulation. Ecarin Clotting Time is proposed for this purpose, but has the major disadvantage of limited availability. There is a point-of-care applicable ecarin-activated test modification for rotational thrombelastometry (ROTEM®) which is sensitive to direct thrombin inhibitors. The aim of the study was to evaluate the correlation between argatroban concentration and this ecarin modified thrombelastometry (EMT).
Methods
In this in vitro experiment, blood drawn from healthy volunteers was spiked with argatroban at clinically relevant concentrations and analyzed with ROTEM® using EMT. The main endpoint was the clotting time (CT).
Results
EMT-CT was prolonged with increasing argatroban concentrations (from 83.3 ± 6.7 s without argatroban to 743.5 ± 138.2 s at 2 μg/ml argatroban). The correlation between argatroban concentration and EMT-CT was high (r = 0.94) and statistically significant (p < 0.01).
Conclusion
These promising preclinical results mandate further clinical research to determine an EMT-CT target range regarding the clinical outcomes of thrombosis and bleeding.
Zusammenfassung
Hintergrund
Ein exaktes Monitoring könnte die individuelle Dosierung und das perioperative Management einer Antikoagulation mit dem direkten Thrombininhibitor Argatroban deutlich erleichtern. Im Prinzip wäre die „Ecarin Clotting Time“, ein Laborgerinnungstest, dafür geeignet; dieser Test wird aber nur von ausgewählten Labors angeboten. Für die bettseitig verfügbare Rotationsthrombelastometrie (ROTEM®) gibt es einen ebenso mit Ecarin aktivierten Testansatz, der für das Vorliegen von direkten Thrombininhibitoren empfindlich ist. Ziel dieser Studie war die Ermittlung der Korrelation zwischen Argatroban-Konzentration und Ecarin-aktivierter Rotationsthrombelastometrie (EMT).
Methodik
In dieser in-vitro Studie wurde Blut von gesunden Probanden mit Argatroban in unterschiedlichen Konzentrationen versetzt und anschließend mittels ROTEM® vermessen. Hauptzielparameter war die Gerinnungszeit (clotting time, CT).
Ergebnisse
Mit steigenden Argatroban Konzentrationen war die EMT CT verlängert (von 83,3 ± 6,7 s ohne Argatroban auf 743,5 ± 138,2 s bei 2 μg/ml Argatroban). Die Korrelation zwischen der Argatroban Konzentration und der EMT CT war hoch (r = 0,94) und statistisch signifikant (p < 0,01).
Schlussfolgerung
Diese Ergebnisse sind vielversprechend; es bedarf aber noch der klinischen Überprüfung und Festlegung eines EMT Zielbereichs im Zusammenhang mit den Endpunkten Thrombose bzw. Blutung.
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Conflict of interest
A potential conflict of interest is stated by ES who received speaker’s honoraria and travel reimbursement from Mitsubishi Pharma Europe Ltd., London, UK and SKL who received travel reimbursement and speaker’s fees for lecturing from Mitsubishi Pharma Europe Ltd., London, UK and an unrestricted grant for an e-learning project among others from TEM Innovations, Munich, Germany.
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Schaden, E., Schober, A., Hacker, S. et al. Ecarin modified rotational thrombelastometry: a point-of-care applicable alternative to monitor the direct thrombin inhibitor argatroban. Wien Klin Wochenschr 125, 156–159 (2013). https://doi.org/10.1007/s00508-013-0327-1
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DOI: https://doi.org/10.1007/s00508-013-0327-1
Keywords
- Anticoagulants
- Argatroban
- Blood coagulation tests
- Thrombelastography
- Monitoring
- Drug
- Prothrombin activation fragments
- Ecarin