α-2-macroglobulin may provide protection from thromboembolic events in antithrombin III-deficient children

Abstract

Antithrombin III (ATIII) deficiency has been implicated in adults as a predisposing factor to thrombosis; however, thromboembolic complications are rare in children with the same deficiency. We hypothesized that because of the elevated levels of plasma α-2-macroglobulin (α2M) throughout childhood, plasmas of ATIII-deficient children inhibit thrombin more efficiently than those of ATIII-deficient adults. In total, 14 ATIII-deficient adults (ages 25 to 46 years), 13 ATIII-deficient children (ages 2 to 13 years), 9 normal children (ages 3 to 15 years), and 16 normal adults were studied. We measured thrombin inhibition in these plasmas, as well as the contributions of ATIII, α2M, and heparin cofactor II (HCII) as thrombin inhibitors in each plasma. 125I-α-thrombin, 25 nmol/L, was added to each plasma (defibrinated with Arvin at 37°C), and 90 seconds later the free thrombin and thrombin-inhibitor complexes were quantitated after sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography, and densitometric scanning. Plasma from ATIII-deficient adults inhibited significantly less thrombin (12.8 ± 0.6 nmol/L) than both normal adults (16.1 ± 0.3 nmol/L, P < .01). There was no significant difference between the total concentration of thrombin inhibited by ATIII-deficient children and either normal adult or normal children groups. In addition, plasmas of ATIII-deficient children inhibited thrombin significantly more efficiently than plasma of ATIII-deficient adults (P < .01). In the ATIII-deficient patients there was a significant correlation between the α2M level and ability to inhibit thrombin (P < .01). We hypothesize that the lower risk of thromboembolic complications in ATIII-deficient children may be due in part to the protective effect of elevated α2M levels during childhood. © 1991 by The American Society of Hematology.