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Selected Publication:
Cvirn, G; Gallistl, S; Koestenberger, M; Kutschera, J; Leschnik, B; Muntean, W.
Alpha 2-macroglobulin enhances prothrombin activation and thrombin potential by inhibiting the anticoagulant protein C/protein S system in cord and adult plasma.
Thromb Res. 2002; 105(5):433-439
Doi: 10.1016%2FS0049-3848%2802%2900042-7
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- Leading authors Med Uni Graz
- Cvirn Gerhard
- Co-authors Med Uni Graz
- Gallistl Siegfried
- Koestenberger Martin
- Leschnik Bettina
- Muntean Eugen
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- Abstract:
- Protein S (PS) is a vitamin K-dependent plasma protein and serves as a cofactor for the anticoagulant activities of activated protein C (APC). We investigated the effects of different PS concentrations on prothrombin activation and thrombin generation in cord and adult plasma containing APC and different amounts of alpha 2-macroglobulin (a2-M). Prothrombin activation was assessed by monitoring the time-course of prothrombin fragment 1+2 (F1+2) generation. Thrombin generation curves were determined by means of a subsampling technique using the chromogenic substrate S-2238. We demonstrate a dose-dependent inhibition of the anticoagulant action of PS by a2-M: suppression of F1+2 and thrombin generation due to addition of PS was stronger in plasma containing low amounts of a2-M than in plasma with elevated a2-M levels. Since no complex formation between a2-M and PS was observed by means of SDS-PAGE, we attribute decreased anticoagulant action of PS at high a2-M levels to enhanced complex formation between APC and a2-M. Thereby, APC is subtracted from its cofactor PS, resulting in suppressed formation of the anticoagulant APC/PS complex. Thus, our data suggest that a2-M, besides its well-known anticoagulant effects, also acts as a procoagulant by suppressing the formation of the anticoagulant APC/PS complex. Our findings have implications particularly on thrombin generation and inhibition in cord plasma, since a2-M levels in newborns are elevated over adult values and the antithrombotic APC/PS pathway is up-regulated at birth. Therefore, elevated levels of a2-M might restrict the up-regulation of the APC/PS pathway.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Dose-Response Relationship, Drug -
- Electrophoresis, Polyacrylamide Gel -
- Fetal Blood -
- Humans -
- Infant, Newborn -
- Kinetics -
- Protein C - antagonists and inhibitors
- Protein S - antagonists and inhibitors
- Prothrombin - metabolism
- Thrombin - metabolism
- alpha-Macroglobulins - pharmacology
- Find related publications in this database (Keywords)
- alpha 2-macroglobulin
- protein S
- protein C
- thrombin potential
- prothrombin activation
- cord and adult plasma