Pathways for bradykinin formation. In HAE, Plm-Glu³¹¹ conversion to Pln-Glu³¹¹ leads to direct digestion of both LK and HK to produce bradykinin. It essentially replaces tissue and plasma kallikreins in their action on LK and HK, respectively. C1 INH (mutated in HAE types 1 and 2) primarily inhibits FXIIa and plasma kallikrein, but weak inhibition of plasmin and tPA may have relevance to HAE-Plm, as well. Professional illustration by Somersault18:24.