SERPINA1 and hemorrhagic disease: A point mutation at position 358 can drastically alter the antiprotease function of the AAT molecule by reducing or changing the specificity of this bond for its target protease; this is best illustrated by the rare mutation of Met358 to arginine (AAT-Pittsburgh) resulting in greatly diminished antielastase activity and markedly increased antithrombin activity that results in a fatal bleeding disorder [87].