Role for a₂-Macroglobulin in Haemostatic Balance

Abstract

THERE are two plasma proteins in human blood which account for most of the natural antithrombin activity, antithrombin III and a₂-macroglobulin, which both react slowly with thrombin and are called progressive antithrombins. The predominant component, antithrombin III, has been purified recently and is an a₂-globulin^1–4; the minor inhibitor, a₂-macroglobulin (a₂-M), which accounts for about 25% of the antithrombin activity of plasma, has some unusual properties. According to Lanchantin⁵ and Steinbuch⁶, it abolishes the clotting activity of thrombin in the fibrinogen test, but does not impair its esterase activity with synthetic substrates such as N-p-tosyl-L-arginine methyl ester. Thus, the a₂-M-thrombin complex is similar to conjugates of a₂-M with other proteases such as trypsin, chymotrypsin and elastase, which are active against synthetic low-molecular substrates^7,8, but show little or no proteolytic activity^7,9.