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. Author manuscript; available in PMC: 2017 Jun 1.
Published in final edited form as: J Allergy Clin Immunol. 2015 Sep 26;137(6):1822–1829.e1. doi: 10.1016/j.jaci.2015.07.041

FIG 5.

FIG 5

Proposed mechanism of angioedema formation in patients with HAE-N. Assuming a source of urokinase and/or tissue plasminogen activator (eg, endothelial cell activation), deficiency of PAI-2 and diminished levels of PAI-1 (in some cases, such as Fig 4, A) can lead to excessive plasmin formation. The connection to the bradykinin-forming cascade is through plasmin activation of Factor XII.37 In those with the Factor XII mutation, susceptibility to plasmin activation can be enhanced. Later steps include conversion of prekallikrein to kallikrein by Factor XIIa or Factor XIIf,37 the kallikrein feedback activation of Factor XII,21,31 and kallikrein cleavage of HK to release bradykinin.