Multifactorial functions of antithrombin in circulating blood and on the cell surface. The interactions between antithrombin (AT) and the endothelium are shown in the figure. The affinity of antithrombin to thrombin and its enzymatic inhibition are increased by the binding of the heparin-binding site of AT to syndecan-4 on the cell surface or externally administered heparins. Thrombin loses its coagulant activity after the formation of a thrombin-antithrombin complex. Other than thrombin, AT inactivates factors Xa and IXa. As for its anti-inflammatory function, AT inactivates thrombin, thereby attenuating the cellular reactions through the activation of protease-activated receptor (PAR)-1.