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 thrombi n 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 inhi bitor in adult plasma. The aim of our study was to examine this assumption by determining time-courses of free thrombin generation and prothrombin act ivation. Additionally, the amount of thrombin complexed to alpha (2)-M was assessed by comparing the heights of the end-level of amidolytic activity c urves (AACs) after extrinsic activation of platelet poor plasma in the pres ence of different concentrations of AT or alpha (2)-M. Increasing the AT co ntent by 30% resulted in significantly suppressed generation of free thromb in and prothrombin fragment 1+2 (F1+2) in cord and adult plasma. In contras t, increasing the alpha (2)-M content in plasma containing physiologic amou nts 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 effe ct of AT supplementation on the end-level of the AACs was significantly hig her 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 prothro mbin activation, our study suggests that the action between alpha (2)-M and thrombin might not be fast enough to prevent thrombin from its feedback ac tivation in both cord and adult plasma and, therefore, in cord and adult pl asma containing physiological amounts of AT alterations of the alpha (2)-M content had no effect on thrombin generation and inhibition. (C) 2001 Elsev ier Science Ltd. All rights reserved.