A Clinically Silent Antithrombin III Defect IN an ann Arbor Family

A familial decrease in activity in plasma protease inhibitor, Antithrombin III (AT III «as observed in three generations. This autosomal trait is not associated with thrombsis. It is a benign abnormality despite AT III functional values of 23% of normal in heparin co-factor assay. The low activity AT III was purified from fresh plasma on a heparm affinity column. Its functional, biochemical and immunochemical properties were studied. In the progressive AT III assay, both proteins behaved similarly. Binding of low activity I¹²⁵ AT III to α₁, thrombin or heparin column was identical Purified and plasma AT III from normal and propositus had the same electrophoretic mobilit on Polyacrylamide gel and by Immunoelectrophoresis (IEP) in 1.5K agar gelsHowever plasma and purified low activity AT III when analyzed by two dimensional (IEP) with heparin placed in the first gel showed one major immunoprecipltate and a much smaller more electronegative one against AT III antiserum. Under identical conditions, purifi normal AT III showed a reversed pattern. On electrofocusing and by immunodiffusion against antiserum to thrombin, the major immunoprecipltate was identified as an AT III thrombin comply. A variant of the propositus’ AT III favors rapid binding of thrombi without need of heparin.