Alpha(2)-macroglobulin levels are high in adult patients with congenital antithrombin deficiency

Antithrombin is responsible for about 80% of the progressive inhibitory act ivity of thrombin in human plasma. The role of other protease inhibitors kn own to inhibit thrombin is not completely clarified. However, their contrib ution may become relevant when antithrombin is low. We elected to investiga te adult patients with congenital antithrombin deficiency to assess the con centration of other naturally occurring thrombin inhibitors such as alpha(2 )-macroglobulin, alpha(1)-antitrypsin, heparin cofactor II, and C-1-inhibit or. The study included 59 patients with congenital antithrombin deficiency with and without a previous history of thrombosis, together with an equal n umber of control subjects matched for age and sex. Statistically significan t differences (patients vs. controls) were observed only for alpha(2)-macro globulin (i.e., 120 vs. 102%? p < 0.01). Further analysis of antithrombin-d eficient carriers with and without a past history of thrombosis showed that alpha(1)-macroglobulin levels were higher than the 90th percentile of cont rol distribution more often in asymptomatic than symptomatic men (odds rati o = 0.04; confidence interval = 0.003-0.60), but not in women (odds ratio = 2.14; confidence interval = 0.35-13.1). In conclusion, results from this c ross sectional study showed that alpha(2)-macroglobulin levels were high in patients with congenital antithrombin deficiency. Furthermore, the high le vels were found more often in asymptomatic than symptomatic men. Whether th is increase provides protection against thrombosis should be evaluated in a prospective study. (C) 2000 Elsevier Science Ltd. All rights reserved.