Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Koestenberger, M; Gallistl, S; Cvirn, G; Baier, K; Leschnik, B; Muntean, W.
Anticoagulant action of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, in umbilical cord and adult plasma: an in vitro examination.
THROMB RES. 2005; 115(1-2): 135-142.
Doi: 10.1016/j.thromres.2004.07.003
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- Führende Autor*innen der Med Uni Graz
- Koestenberger Martin
- Co-Autor*innen der Med Uni Graz
- Cvirn Gerhard
- Gallistl Siegfried
- Leschnik Bettina
- Muntean Eugen
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- Abstract:
- INTRODUCTION:This study was performed to compare the anticoagulant activity of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, in umbilical cord plasma with that in adult plasma. In contrast with the most frequently administered anticoagulants, the heparins, melagatran acts independently of antithrombin (AT). As a consequence, administration of melagatran is of special interest in neonates, who have physiologically low levels of AT. MATERIALS AND METHODS: Plasma samples were activated under high (as used in standard clotting assays) and low (more comparable with the physiological milieu) coagulant challenge. In the absence of melagatran, adult plasma clotted significantly faster than umbilical cord plasma under high coagulant challenge. Conversely, under low coagulant challenge, clotting of adult plasma was significantly delayed compared with umbilical cord plasma. For both high and low coagulant challenges, clotting times increased and prothrombin fragment 1.2 and thrombin-antithrombin (TAT) formation decreased with melagatran in a concentration-dependent fashion in umbilical cord and adult plasma. With increasing melagatran concentrations, the quotient between prothrombin fragment 1.2 and TAT formation increased in adult and umbilical cord plasma under both high and low coagulant challenges. RESULTS AND CONCLUSIONS: Our in vitro results cannot be directly extrapolated to clinical efficacy, but assessing the degree of inhibition of thrombin generation may be a useful surrogate for selecting effective doses of ximelagatran for in vivo studies in neonates with thromboembolic complications.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Anticoagulants - pharmacology
- Antithrombin III - analysis
- Azetidines - analysis
- Benzylamines - analysis
- Blood - drug effects
- Blood Coagulation - drug effects
- Dose-Response Relationship, Drug - drug effects
- Fetal Blood - drug effects
- Glycine - analogs and derivatives
- Humans - analogs and derivatives
- Infant, Newborn - analogs and derivatives
- Peptide Fragments - blood
- Peptide Hydrolases - blood
- Prothrombin - blood
- Thrombin - antagonists and inhibitors
- Find related publications in this database (Keywords)
- melagatran
- oral direct thrombin inhibitor
- ximetagatran
- umbilical cord plasma
- adult plasma