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Ecarin modified rotational thrombelastometry: a point-of-care applicable alternative to monitor the direct thrombin inhibitor argatroban

Die Ecarin-aktivierte Rotationsthrombelastometrie als bettseitig verfügbares Monitoring für den direkten Thrombininhibitor Argatroban

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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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References

  1. Warkentin TE, Greinacher A, Koster A, Lincoff AM, American College of Chest Physicians. Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians evidence-based clinical practice guidelines. 8th ed. Chest. 2008;133(Suppl 6):340–80.

    Article  Google Scholar 

  2. Schaden E, Kozek-Langenecker SA. Direct thrombin inhibitors: pharmacology and application in intensive care medicine. Int Care Med. 2010;36:1127–37.

    Article  CAS  Google Scholar 

  3. Luddington RJ. Thrombelastography/thrombelastometry. Clin Lab Haematol. 2005;27:81–90.

    Article  PubMed  CAS  Google Scholar 

  4. Kozek-Langenecker SA. Management of massive operative blood loss (review). Minerva Anestesiol. 2007;73:401–15.

    PubMed  CAS  Google Scholar 

  5. Mittermayr M, Margreiter J, Velik-Salchner C, Klingler A, Streif W, Fries D, et al. Effects of protamine and heparin can be detected and easily differentiated by modified thrombelastography (Rotem®): an in vitro study. Br J Anaesth. 2005;95:310–6.

    Article  PubMed  CAS  Google Scholar 

  6. Schaden E, Schober A, Hacker S, Spiss C, Chiari A, Kozek-Langenecker S. Determination of enoxaparin with rotational thrombelastometry using the prothrombinase-induced clotting time reagent. Blood Coagul Fibrinolysis. 2010;21:256–61.

    Article  PubMed  CAS  Google Scholar 

  7. Engström M, Rundgren M, Schött U. An evaluation of monitoring possibilities of argatroban using rotational thrombelastometry and activated partial thromboplastin time. Acta Anaesth Scand. 2009;1:1–6.

    Google Scholar 

  8. Swan S, Hursting M. The pharmacokinetics and pharmacodynamics of argatroban: effects of age, gender and hepatic or renal dysfunction. Pharmacotherapy. 2000;20:318–29.

    Article  PubMed  CAS  Google Scholar 

  9. Sucker C, Zotz RB, Görlinger K, Hartmann M. Rotational thrombelastometry for the bedside monitoring of recombinant hirudin. Acta Anaesth Scand. 2008;52:358–62.

    Article  PubMed  CAS  Google Scholar 

  10. Francis JL, Hursting MJ. Effect of argatroban on the activated partial thromboplastin time: a comparison of 21 commercial reagents. Blood Coagul Fibrinolysis. 2005;16:251–7.

    Article  PubMed  CAS  Google Scholar 

  11. Wenzel C, Stoiser B, Locker G, Laczika K, Quehenberger P, Kapiotis S, et al. Frequent development of lupus anticoagulants in critically ill patients treated under intensive care conditions. Crit Care Med. 2002;30:763–70.

    Article  PubMed  CAS  Google Scholar 

  12. Love JE, Ferrell C, Chandler WL. Monitoring direct thrombin inhibitors with a plasma diluted thrombin time. Thromb Haemost. 2007;98:234–42.

    PubMed  CAS  Google Scholar 

  13. Walenga JM, Fasanella AR, Iqbal O, Hoppensteadt DA, Ahmad S, Wallis DE, et al. Coagulation laboratory testing in patients treated with argatroban. Semin Thromb Haemost. 1999;25(Suppl 1):61–6.

    CAS  Google Scholar 

  14. Siegmund R, Boer K, Poeschel K, Wolf G, Deufel T, Kiehntopf M. Comparison of the ecarin chromogenic assay and different aPTT assays for the measurement of argatroban concentrations in plasma from healthy individuals and from coagulation factor deficient patients. Thromb Res. 2008;123:159–65.

    Article  PubMed  CAS  Google Scholar 

  15. Lange U, Nowak G, Bucha E. Ecarin Chromogenic Assay—a new method for quantitative determination of direct thrombin inhibitors like hirudin. Pathophysiol Haemost Thromb. 2003;33:184–91.

    Article  PubMed  CAS  Google Scholar 

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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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Correspondence to Eva Schaden MD.

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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

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