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Semin Thromb Hemost 2002; 28(5): 425-430
DOI: 10.1055/s-2002-35282
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Methods for the Monitoring of Direct Thrombin Inhibitors

Gerd Hafner1 , Markus Roser2 , Matthias Nauck2
  • 1Zentrum für Labormedizin und Mikrobiologie, Essen, Germany
  • 2Institut für Klinische Chemie, Klinikum der Ernst-Moritz-Arndt-Universität, Greifswald, Germany
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Publication History

Publication Date:
06 November 2002 (online)

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ABSTRACT

Direct thrombin inhibitors are available for prophylactic as well as therapeutic purposes. Application of hirudin in therapeutic doses has been shown to require drug monitoring. Currently, most experience is available for recombinant hirudin, but the principle aspects of drug monitoring are the same for all direct thrombin inhibitors. Most frequently, activated partial thromboplastin time (aPTT) and modifications of the activated clotting time (ACT) have been used for the monitoring of hirudin therapy. However, these methods are insensitive at plasma levels higher than 0.6 mg/L of hirudin, so that overdoses may be missed despite monitoring. Correlations between ecarin clotting time (ECT), enzyme immunoassays, and chromogenic substrate assays on one side and global tests on the other side are poor. Fully automated chromogenic substrate-based assays, also available as point-of-care tests (POCT), are more precise and sensitive and are not disturbed by interferents such as heparin and antithrombin. Good correlations can be observed between chromogenic assays and the ECT performed in plasma or whole blood samples. ECT can also be determined with POCT systems. Test characteristics such as imprecision and measuring range are comparable to those of the chromogenic assays. In conclusion, therapy with direct thrombin inhibitors should be monitored with chromogenic assays or ECT.

KEYWORDS

Hirudin - direct thrombin inhibitors - monitoring - ecarin clotting time - chromogenic assay

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