Update on antithrombin I (fibrin).
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 on each gamma' chain through interaction with thrombin exosite 2. The latter reaction results in allosteric changes that down-regulate thrombin catalytic activity. Antithrombin I deficiency (afibrinogenemia), defective thrombin binding to fibrin (antithrombin I defect) found in certain dysfibrinogenemias (e.g. fibrinogen Naples 1), or a reduced plasma gamma' chain content (reduced antithrombin I activity), predispose to intravascular thrombosis.