Antithrombin III: Critical Review of Assay Methods. Significance of Variations in Health and Disease

Thrombin and factor Xa which are added to plasma are inactivated by At-III. The reactions are accelerated by heparin, permitting assay systems which rapidly measure At-III content of diluted plasma. Without heparin, the (slow) inactivation rate may be measured. The review of existing activity assays(fibrinogen or chro-mogenic substrates), and semiquantitative assays, will focus upon their usefulness and limitations, and to the correlation to results of immunoassay. In health, a narrow range of At-III concentration (and activity) is found. The level is low in infancy. Fertile women have on the average lower levels than men. In old age the level tends to drop. In the normal material that will be reported, one man was the propositus of a “new” family with At-III deficiency and thrombophilia. In a clinical material (n=2000), studied with amidolytic assay, subnormal At-III levels were found in hereditary deficiency, liver cirrhosis, disseminated intravascular coagulation and in some cases with acute thrombosis. Piasma samples containing soluble fibrin (positive ethanol gelation test) were classified as to the degree of hypercoagulation according to the values of other coagulation tests (grade 1-4, grade 4=DIC). The mean At-III plasma level decreased with increasing degree of hypercoagulation. Due to its high accuracy and simplicity, we have chosen the amidolytic activity assay with heparin and thrombin (Thromb. Res. 6, 287, 1975) for routine work.