Anticoagulant action of melagatran: a comparison between neonates and adults using calibrated automated thrombography (CAT).
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 micromol/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 (IC(50)) of melagatran were required to double the lag times (0.44+/-0.04 micromol/l vs. 0.52+/-0.05 micromol/l) or to double the TTPs (0.91+/-0.08 micromol/l vs. 1.06+/-0.09 micromol/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 (IC(50)) of melagatran were required to suppress ETPs (0.27+/-0.03 micromol/l vs. 0.70+/-0.06 micromol/l) or thrombin peak heights by 50% (0.29+/-0.03 micromol/l vs. 0.53+/-0.04 micromol/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.
Cvirn
Gerhard
G
Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Harrachgasse 21/II, 8010, Graz, Austria. gerhard.cvirn@meduni-graz.at
Cimenti
Christina
C
Kutschera
Joerg
J
Ferstl
Ulrika
U
Wagner
Thomas
T
Muntean
Wolfgang
W
Jurgens
Gunther
G
Gallistl
Siegfried
S
Koestenberger
Martin
M
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D001384:Azetidines / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D005260:Female; D005312:Fetal Blood / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010949:Plasma / Q000187:drug effects; D013918:Thrombin Time
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; C109573:melagatran