title: Alpha(2)-macroglobulin levels are high in adult patients with congenital antithrombin deficiency.
abstract: Antithrombin is responsible for about 80% of the progressive inhibitory activity of thrombin in human plasma. The role of other protease inhibitors known to inhibit thrombin is not completely clarified. However, their contribution may become relevant when antithrombin is low. We elected to investigate adult patients with congenital antithrombin deficiency to assess the concentration of other naturally occurring thrombin inhibitors such as alpha(2)-macroglobulin, alpha(1)-antitrypsin, heparin cofactor II, and C(1)-inhibitor. The study included 59 patients with congenital antithrombin deficiency with and without a previous history of thrombosis, together with an equal number of control subjects matched for age and sex. Statistically significant differences (patients vs. controls) were observed only for alpha(2)-macroglobulin (i.e., 120 vs. 102%, p<0.01). Further analysis of antithrombin-deficient carriers with and without a past history of thrombosis showed that alpha(2)-macroglobulin levels were higher than the 90th percentile of control distribution more often in asymptomatic than symptomatic men (odds ratio=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 cross sectional study showed that alpha(2)-macroglobulin levels were high in patients with congenital antithrombin deficiency. Furthermore, the high levels were found more often in asymptomatic than symptomatic men. Whether this increase provides protection against thrombosis should be evaluated in a prospective study.
authors.affiliation: Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, Department of Internal Medicine, University and IRCCS Maggiore Hospital, Milano, Italy. armando.tripodi@unimi.it
authors.forename: A
authors.initials: A
authors.lastname: Tripodi
authors.forename: V
authors.initials: V
authors.lastname: Chantarangkul
authors.forename: V
authors.initials: V
authors.lastname: De Stefano
authors.forename: P
authors.initials: P
authors.lastname: Mannucci
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020152:Antithrombin III Deficiency / Q000097:blood* / Q000150:complications / Q000151:congenital*; D016022:Case-Control Studies; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D005260:Female; D015844:Heparin Cofactor II / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D013927:Thrombosis / Q000097:blood / Q000209:etiology; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism*
chemical_list: D003174:Complement C1 Inactivator Proteins; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins; D015844:Heparin Cofactor II