alpha 2Antiplasmin (alpha,2AP), also known as alpha 2Plasmin Inhibitor (alpha 2PI), is a member of the SERPIN family of proteinase inhibitors and the primary inhibitor of the enzyme plasmin in blood. It is produced in the liver and circulates in plasma at ~70ug/ml (~1uM). alpha 2AP is a single chain molecule with a mass of 67kD as determined by SDS-PAGE. The primary target enzyme for alpha 2AP is plasmin, but alpha 2AP also acts as secondary or “backup” inhibitor of activated F.XI, activated Protein C and trypsin. Inhibition of these enzymes by alpha 2AP occurs by proteolytic cleavage after Arg364 with subsequent rapid formation of a stable, inactive 1:1 enzyme-alpha 2AP complex. alpha 2AP also acts to regulate fibrinolysis by binding to the lysine binding sites on plasminogen thus competitively inhibiting plasminogen binding to fibrin. About 30% of alpha 2AP present in plasma is partially degraded and lacks a peptide in the carboxyl region that contains the plasminogen-binding site. This form of alpha 2AP (~65kD) has a reduced rate of plasmin inhibition and has been referred to as the “slow form” of alpha 2AP. During fibrin formation, a portion of circulating alpha 2AP is cross-linked to the alpha -chain of fibrin by activated factor XIII, and this linking of plasmin inhibitor to the plasmin substrate provides an additional measure of protection to the fibrin clot from proteolysis by plasmin.