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Vol. 33, No. 4, 2003
Issue release date: July–August 2003
Pathophysiol Haemost Thromb 2003/04;33:173–183

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

 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)

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