title: Congenital antithrombin III deficiency: insights into the pathogenesis of the hypercoagulable state and its management using markers of hemostatic system activation.
abstract: Hereditary antithrombin III (ATIII) deficiency predisposes patients to venous thrombosis. The prothrombin fragment F1+2 radioimmunoassay demonstrates that many asymptomatic patients with this disorder not receiving antithrombotic therapy have elevated plasma factor Xa activity. The hemostatic system hyperactivity as measured by this assay could be specifically corrected by rising plasma ATIII levels of several persons into the normal range. This indicates that the prethrombotic state can be defined as an imbalance between the production and inhibition of factor Xa enzymatic activity. The effects of warfarin on factor Xa enzymatic activity in persons with congenital ATIII deficiency have also been evaluated. At equivalent intensities of oral anticoagulation, the mean plasma F1+2 level in patients with ATIII deficiency was significantly elevated as compared with anticoagulated persons without this inherited thrombotic disorder. It is concluded that the effect of warfarin on hemostatic system activation is modulated by the endogenous heparan sulfate-ATIII mechanism. This suggests that the F1+2 radioimmunoassay can be employed to improve the understanding of the hypercoagulable state associated with antithrombin III deficiency as well as to develop more effective treatment strategies to prevent thromboembolic events in patients with this disorder.
authors.affiliation: Charles A. Dana Research Institute, Boston, Massachusetts.
authors.forename: K A
authors.initials: KA
authors.lastname: Bauer
authors.forename: R D
authors.initials: RD
authors.lastname: Rosenberg
mesh_terms: D020152:Antithrombin III Deficiency; D015951:Factor Xa / Q000032:analysis; D006487:Hemostasis; D006801:Humans; D011863:Radioimmunoassay; D013924:Thrombophlebitis / Q000235:genetics* / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D014859:Warfarin; D015951:Factor Xa