Alpha 2-macroglobulin enhances prothrombin activation and thrombin potential by inhibiting the anticoagulant protein C/protein S system in cord and adult plasma
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- 作者：Cvirn ; Gerhard ; Gallistl ; Siegfried ; Koestenberger ; Martin ; Kutschera ; Joerg ; Leschnik ; Bettina ; et. al.
- 关键词：Alpha 2-macroglobulin ; Protein S ; Protein C ; Thrombin potential ; Prothrombin activation ; Cord and adult plasma ; a2-M ; alpha 2-macroglobulin ; APC ; activated protein C ; AT ; antithrombin ; TP ; thrombin potential ; PS ; protein S ; F1+2 ; prothrombin fragment 1+2
- 刊名：Thrombosis Research
- 出版年：2002
- 出版时间：March 1, 2002
- 年：2002
- 卷：105
- 期：5
- 页码：433-439
- 全文大小：140 K
文摘
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.