The exploration for the potential use of modified antitrypsins with an altered inhibitory spectrum has been guided by the discovery of a natural variant of α1-AT, known as Pittsburgh (α1-AT-PIT), found in a patient who had a severe bleeding disorder caused by mutation of the P1 reactive center residue of antitrypsin from methionine to arginine [37]. Here, SERPINA1 is linked to hemorrhagic disease.