Antithrombin (AT) deficiency increases the risk of thrombosis. Current evidence shows that some SERPINC1 mutations responsible for antithrombin deficiency often present a slightly decreased or normal activity and therefore could not be detected by functional tests. This study was designed to compare activity assays and direct genetic analyses in identifying hereditary antithrombin deficiency. I...

The role of the family history as a tool for the diagnosis of inherited thrombophilia has not been established. Several authors have indicated that a positive family history is not a good predictor of inherited abnormalities such as antithrombin III deficiency, or deficiencies of protein C or protein S. We have tried to approach the family history in a quantitative way. To this end we used the ...

An antithrombin III deficient infant presented with iliac vein thrombosis, apparently precipitated by an overtight nappy. Venous thrombosis is unusual, both in normal and in antithrombin III deficient children, but children with venous thrombosis should have their natural anticoagulants assayed and obvious risk factors avoided.

Antithrombin I (fibrin) is an important inhibitor of thrombin generation that functions by sequestering thrombin in the forming fibrin clot, and also by reducing the catalytic activity of fibrinbound thrombin. Thrombin binding to fibrin takes place at two classes of non-substrate sites: 1) in the fibrin E domain (two per molecule) through interaction with thrombin exosite 1; 2) at a single site...

Plasma levels of antithrombin-heparin cofactor, determined by heparin-dependent antithrombin assay, and antithrombin III antigen were measured in 22 members of a large kindred predisposed to venous thrombosis. While 11 members had reduced plasma levels of both antithrombin-heparin cofactor and antithrombin III antigen, the levels of antithrombin-heparin cofactor were always greater than the lev...

Purification of vitronectin by identical procedures from serum instead of plasma results in the coisolation of an additional protein component with mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of 82 kDa. We show that this component is the thrombin-antithrombin III complex based on the following evidence. Similar to a complex constructed using purified thrombi...

Using DNA probes in a structural study of the antithrombin III gene locus we found no evidence of gene deletion in two British kindreds with inherited antithrombin III deficiency. However, linkage analysis between a common DNA polymorphism and the antithrombin III deficiency trait showed that the defect lies at or close to the antithrombin III structural gene. The lod score for linkage within t...

Antithrombin-III-Hamilton is a structural mutant of antithrombin III with defective serine protease reactivity, demonstrable in three members of a French Canadian family. The propositus, a 54-year-old man with a history of recurrent thromboembolic events, and his two asymptomatic grown children are heterozygous for the mutant antithrombin III gene. In all three individuals, the immunoreactive a...

We identified a novel mechanism of hereditary thrombosis associated with antithrombin resistance, with a substitution of arginine for leucine at position 596 (p.Arg596Leu) in the gene encoding prothrombin (called prothrombin Yukuhashi). The mutant prothrombin had moderately lower activity than wild-type prothrombin in clotting assays, but the formation of thrombin-antithrombin complex was subst...

The presence of an antithrombin in normal plasma and serum has been known for many years. In 1892 Schmidt postulated its existence when he observed the rapid disappearance of thrombin from blood after coagulation. Tests have been devised enabling the titre of antithrombin to be determined. Most of these tests depend on the inactivation of serial dilutions of thrombin of known concentration by t...