FXII-Lys/Arg³⁰⁹ results in enhanced kallikrein activation leading to bradykinin (BK) release from HMWK that is unable to be effectively inhibited by C1-INH. The variant FXII-Lys/Arg³⁰⁹ may be cleaved after residues 309 by thrombin, FXIa, and plasmin, in circumstances such as trauma, to give rise to a nonactivated truncated form of FXII, denoted δFXII, which contains the catalytic domain without the heavy chain of FXII. There are 2 mechanisms that give rise to enhanced kallikrein generation: first, δFXII can convert PK to kallikrein more efficiently than native FXII (with a 2.5-fold increase in catalytic efficiency) thereby generating more kallikrein in the early stages of reciprocal FXII/PK activation. Second, δFXII is a better substrate than FXII for kallikrein (15-fold greater catalytic efficiency). As a result, increased concentrations of δFXIIa will be generated, causing further PK activation, ultimately resulting in enhanced kallikrein generation. Kallikrein will cleave HMWK, releasing BK that will bind to BK receptors and induce vascular permeability leading to edema. Professional illustration by Somersault18:24.