Effects of alpha(2)-macroglobulin and antithrombin on thrombin generation and inhibition in cord and adult plasma.
Thromboembolic complications rarely occur during infancy and childhood. It has been reported that increased capacity of cord plasma to inhibit thrombin due to elevated alpha(2)-macroglobulin (alpha(2)-M) levels may in part provide protection from thrombosis. In antithrombin (AT)-deficient plasma, alpha(2)-M exhibits anticoagulant action by complexing substantial amounts of generated free thrombin. It has been suggested that alpha(2)-M has the same impact on thrombin inhibition as AT, the most important thrombin inhibitor in adult plasma. The aim of our study was to examine this assumption by determining time-courses of free thrombin generation and prothrombin activation. Additionally, the amount of thrombin complexed to alpha(2)-M was assessed by comparing the heights of the end-level of amidolytic activity curves (AACs) after extrinsic activation of platelet poor plasma in the presence of different concentrations of AT or alpha(2)-M. Increasing the AT content by 30% resulted in significantly suppressed generation of free thrombin and prothrombin fragment 1+2 (F1+2) in cord and adult plasma. In contrast, increasing the alpha(2)-M content in plasma containing physiologic amounts of AT by the same percentage had no effect on free thrombin generation and on F1+2 generation in both cord and adult plasma. In addition, the effect of AT supplementation on the end-level of the AACs was significantly higher compared to the effect of alpha(2)-M supplementation. Since alpha(2)-M, in contrast to AT, had no effect on free thrombin generation and prothrombin activation, our study suggests that the action between alpha(2)-M and thrombin might not be fast enough to prevent thrombin from its feedback activation in both cord and adult plasma and, therefore, in cord and adult plasma containing physiological amounts of AT alterations of the alpha(2)-M content had no effect on thrombin generation and inhibition.
Department of Pediatrics and Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Graz, Austria. gerhard.cvirn@klinikum-graz.at
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Cvirn
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Gallistl
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Muntean
D000328:Adult; D000367:Age Factors; D000991:Antithrombins / Q000494:pharmacology*; D005312:Fetal Blood; D006801:Humans; D007231:Infant, Newborn; D013917:Thrombin / Q000378:metabolism*; D000511:alpha-Macroglobulins / Q000494:pharmacology*
D000991:Antithrombins; D000511:alpha-Macroglobulins; D013917:Thrombin