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Anticoagulant action of melagatran: a comparison between neonates and adults using calibrated automated thrombography (CAT)

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Abstract

In the present study, we comparatively evaluated the anticoagulant efficacy of the new direct thrombin inhibitor melagatran in cord vs. adult plasma. In contrast to heparin, melagatran does not require antithrombin as a cofactor. Thus, anticoagulant treatment with melagatran is of special interest in neonatal patients, whose plasma is relatively deficient in antithrombin. We evaluated the anticoagulant action of increasing amounts of melagatran (0.1–2.0 μmol/l) in both cord and adult plasma by means of calibrated automated thrombography (CAT) with respect to the lag time until the onset of thrombin formation, time to thrombin peak maximum (TTP), endogenous thrombin potential (ETP), and thrombin peak height. Melagatran exhibited approximately the same ability to prolong lag times or TTPs in both cord and adult plasma. Similar concentrations (IC50) of melagatran were required to double the lag times (0.44±0.04 μmol/l vs. 0.52±0.05 μmol/l) or to double the TTPs (0.91±0.08 μmol/l vs. 1.06±0.09 μmol/l) in cord vs. adult plasma. Melagatran exhibited a higher ability to suppress ETPs or thrombin peak heights in cord vs. adult plasma. Markedly lower concentrations (IC50) of melagatran were required to suppress ETPs (0.27±0.03 μmol/l vs. 0.70±0.06 μmol/l) or thrombin peak heights by 50% (0.29±0.03 μmol/l vs. 0.53±0.04 μmol/l) in cord vs. adult plasma. We conclude that our results suggest a higher ability of melagatran to suppress thrombin formation in cord vs. adult plasma. Thus, lower amounts of melagatran might be required in neonates undergoing antithrombotic therapy.

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Abbreviations

CAT:

Calibrated automated thrombography

DTI:

direct thrombin inhibitor

ETP:

endogenous thrombin potential

PPP:

platelet-poor plasma

S.D.:

standard deviation

TF:

tissue factor

TTP:

time to peak

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Acknowledgment

This study was supported by a grant from the Franz Lanyar-Stiftung.

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Authors and Affiliations

  1. Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Harrachgasse 21/II, 8010, Graz, Austria

    Gerhard Cvirn, Ulrika Ferstl & Gunther Jurgens

  2. Department of Pediatrics, Medical University of Graz, 8036, Graz, Austria

    Christina Cimenti, Joerg Kutschera, Wolfgang Muntean, Siegfried Gallistl & Martin Koestenberger

  3. Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, 8036, Graz, Austria

    Thomas Wagner

Authors
  1. Gerhard Cvirn
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  2. Christina Cimenti
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  3. Joerg Kutschera
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  4. Ulrika Ferstl
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  5. Thomas Wagner
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  6. Wolfgang Muntean
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  7. Gunther Jurgens
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  8. Siegfried Gallistl
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  9. Martin Koestenberger
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Correspondence to Gerhard Cvirn.

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Cvirn, G., Cimenti, C., Kutschera, J. et al. Anticoagulant action of melagatran: a comparison between neonates and adults using calibrated automated thrombography (CAT). Eur J Pediatr 166, 427–431 (2007). https://doi.org/10.1007/s00431-006-0253-6

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  • DOI: https://doi.org/10.1007/s00431-006-0253-6

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