Whereas inactivating mutations and deficiencies of alpha-1-antiproteinase only resulted in elastase-induced tissue damage, such as skin hyperextensibility [47], chronic obstructive pulmonary disease and liver disease [46] in humans, but not in bleeding disorders, the Pittsburgh mutation of alpha-1-antiproteinase results in a fatal haemorrhagic diathesis due to greatly enhanced protease-inhibitory effects on thrombin, thus blocking the coagulation cascade [46]. The gene discussed is SERPINA1; the disease is liver disorder.