α2-MACROGLOBULIN AND ANTITHROMBIN III ARE EQUALLY IMPORTANT INHIBITORS OF THROMBIN IN NEONATAL PLASMA

Healthy newborn infants rarely Buffer from thrombosis, despite their low plasma antithrombin III (ATIII) levels. In adults, ATIII is the main inhibitor of thrombin; α2-macroglobulin (α2M) and heparin-cofactor (HCII) are of lesser importance. In infants and children, plasma α2M concentrations are higher than in adults and exceed ATIII activities by about 2-fold. Therefore we determined the contribution of all 3 antiproteases to the inhibition of 125I-thrombin in defibrinated pooled adult and cord plasmas. Thrombin-inhibitor complexes were quantitated by SDS-PAGE. Thrombin was inhibited to a similar extent in both plasmas. The proportions of thrombin complexed to α2M, ATIII and HCII are summarized below:Values are means (SD) of 18 determinations/pooled plasma. The observed differences in distributions are consistent with calculated velocities which favour the complex formation between α2M and thrombin in neonatal plasma. Upon addition of heparin, ATIII became the most important inhibitor of thrombin in cord plasma.Conclusion: In the absence of heparin, α2M and ATIII are equally important inhibitors of thrombin in neonatal plasma. Speculation; High α2M plasma concentrations may protect healthy newborn infants and possibly also ATIII deficient children from thrombosis.