Vol. 33, No. 4, 2003
Issue release date: July–August 2003
Pathophysiol Haemost Thromb 2003/04;33:173–183
(DOI:10.1159/000081505)
Review Paper
Add to my selection

The Ecarin Clotting Time, a Universal Method to Quantify Direct Thrombin Inhibitors

Nowak G.
Research Group ‘Pharmacological Haemostaseology’, Medical Faculty, Friedrich Schiller University Jena, Jena, Germany
email Corresponding Author


 goto top of outline Key Words

  • Ecarin clotting time
  • Meizothrombin generation test
  • Direct thrombin inhibitor
  • r-Hirudin

 goto top of outline Abstract

The ecarin clotting time (ECT) is a meizothrombin generation test that allows for precise quantification of direct thrombin inhibitors. The ECT has demonstrated its usefulness for more than 10 years in biochemical-pharmacological investigations as well as in clinical research and in the clinical routine. It has proved valuable especially as a drug-monitoring method in r-hirudin therapy. This test has been adjusted to clinical requirements by numerous modifications. Following the description of the biochemical background and the measuring principle of the ECT, this article gives a short survey of several modifications of the ECT for both preclinical and clinical use, e.g., for biochemical investigations, as a point-of-care method and for cardiac surgery. Advantages and disadvantages of these methods are discussed.

Copyright © 2004 S. Karger AG, Basel


 goto top of outline References
  1. Griessbach U, Stürzebecher J: Assay of hirudin in plasma using chromogenic thrombin substrate. Thromb Res 1986;37:347–350.
  2. Nowak G, Bucha E: Ecarin-induced meizothrombin formation – an efficient antidote of hirudin. Thromb Res 1992;65:S157.
  3. Nowak G, Bucha E: A new method for the therapeutical monitoring of hirudin. Thromb Haemost 1993;69:1306.

    External Resources

  4. Nowak G, Bucha E: Quantitative determination of hirudin in blood and body fluids. Semin Thromb Hemost 1996;22:197–202.
  5. Boskovic DS, Bajzar LS, Nesheim ME: Channeling during prothrombin activation. J Biol Chem 2001;276:28685–28693.
  6. Nowak G, Bucha E: Prothrombin conversion intermediate effectively neutralizes toxic levels of hirudin. Thromb Res 1995;80:317–325.
  7. Nowak G: Monitoring of the action of antithrombin agents by ecarin clotting time; in Pifarré R (ed): New Anticoagulants for the Cardiovascular Patient. Philadelphia, Hanley & Belfus, 1997, pp 539–550.
  8. Pötzsch B, Hund S, Madlener K, Unkrig C, Müller-Berghaus G: Monitoring of recombinant hirudin – assessment of a plasma-based ecarin clotting time assay. Thromb Res 1997;86:373–383.
  9. Pötzsch B, Madlener K, Seelig C, Riess CF, Greinacher A, Müller-Berghaus G: Monitoring of r-hirudin anticoagulation during cardiopulmonary bypass – assessment of the whole blood ecarin clotting time. Thromb Haemost 1997;77:920–925.
  10. Mende K, Petoukhova O, Koulitchkova V, Schaub GA, Lange U, Kaufmann R, Nowak G: Dipetalogastin, a potent thrombin inhibitor from the bloodsucking insect Dipetalogaster maximus. CDNA cloning, expression and characterization. Eur J Biochem 1999;266:583–590.
  11. Novak G, Bucha E, Kossmehl A: Quantitative determination of synthetic thrombin inhibitors using Ecarin Clotting Time. Ann Hematol 1998;76(suppl 1):A51.
  12. Esslinger HU, Bucha E, Pöschel K, Jansa U, Schindler S, Stein G, Nowak G: Pharmacokinetics of PEG-hirudin in subjects with various degrees of renal function. Ann Hematol 1998;76(suppl 1):P278.
  13. Breddin HK, Radziwon P, Esslinger HU: Thrombin inhibition enhances aspirin-induced bleeding time prolongation. Circulation 1996;94:I-267.
  14. Lopez ML, Nowak G: Special pharmacokinetics of dipetarudin suggests a potential antitumor activity of this thrombin inhibitor. Anticancer Drug 2004,15:145–149.
  15. Kaufmann R, Zieger M, Tausch S, Henklein P, Nowak G: Meizothrombin, an intermediate of prothrombin activation, stimulates human glioblastoma cells by interaction with PAR-1-type thrombin receptors. J Neurosci Res 2000;59:643–648.
  16. Lindhoff-Last E, Piechottka GP, Rabe F, Bauersachs R: Hirudin determination in plasma can be strongly influenced by the prothrombin level. Thromb Res 2000;100:55–60.
  17. Lange U, Wiesenburg A, Olschewski A, Steinmetzer T, Nowak G, Bucha E: Ecarin chromogenic assay (ECA) – a new chromogenic assay useful for clinical monitoring of direct thrombin inhibitors like hirudin. Ann Hematol 2002;81(suppl 1):A49.
  18. Riess FC, Pötzsch B, Müller-Berghaus G: Recombinant hirudin as an anticoagulant during cardiac surgery; in Pifarré R (ed): New Anticoagulants for the Cardiovascular Patient. Philadelphia, Hanley & Belfus, 1997, pp 197–221.

 goto top of outline Author Contacts

Prof. Dr. Götz Nowak
Friedrich Schiller University Jena, Medical Faculty
Research Group ‘Pharmacological Haemostaseology’
Drackendorfer Strasse 1, DE–07747 Jena (Germany)
Tel. +49 3641 932 57 00, Fax +49 3641 932 57 02, E-Mail goetz.nowak@med.uni-jena.de


 goto top of outline Article Information

This review is dedicated to the 80th birthday of Fritz Markwardt

Received: July 26, 2004
Accepted after revision: September 14, 2004
Number of Print Pages : 11
Number of Figures : 11, Number of Tables : 0, Number of References : 18


 goto top of outline Publication Details

Pathophysiology of Haemostasis and Thrombosis

Vol. 33, No. 4, Year 2003 (Cover Date: July-August 2003)

Journal Editor: J. Rosing, Maastricht
ISSN: 1424–8832 (print), 1424–8840 (Online)

For additional information: http://www.karger.com/pht


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.