Effects of α 2-Macroglobulin and Antithrombin on Thrombin Generation and Inhibition in Cord and Adult Plasma

Abstract

Thromboembolic complications rarely occur during infancy and childhood. It has been reported that increased capacity of cord plasma to inhibit thrombin due to elevated α 2-macroglobulin (α 2-M) levels may in part provide protection from thrombosis. In antithrombin (AT)-deficient plasma, α 2-M exhibits anticoagulant action by complexing substantial amounts of generated free thrombin. It has been suggested that α 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 α 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 α 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 α 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 α 2-M supplementation. Since α 2-M, in contrast to AT, had no effect on free thrombin generation and prothrombin activation, our study suggests that the action between α 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 α 2-M content had no effect on thrombin generation and inhibition.