DiaPharma Group, Inc.

alpha2-Antiplasmin (alpha2-AP), also known as alpha2-Plasmin Inhibitor (alpha2-PI), 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 ~70 micrograms/milliliters (~1 micrometers). alpha2-AP is a single chain molecule with a mass of 67 kDa as determined by SDS-PAGE. The primary target enzyme for alpha2-AP is plasmin, but alpha2-AP also acts as secondary or "backup" inhibitor of activated FXI, activated Protein C and trypsin. Inhibition of these enzymes by alpha2-AP occurs by proteolytic cleavage after Arg³⁶⁴with subsequent rapid formation of a stable, inactive 1:1 enzyme-alpha2-AP complex. Alpha2-AP also acts to regulate fibrinolysis by binding to the lysine binding sites on plasminogen thus competitively inhibiting plasminogen binding to fibrin. About 30% of alpha2-AP present in plasma is partially degraded and lacks a peptide in the carboxyl region that contains the plasminogen-binding site. This form of alpha2-AP (~65 kDa) has a reduced rate of plasmin inhibition and has been referred to as the "slow form" of alpha2-AP. During fibrin formation, a portion of circulating alpha2-AP 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.