Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency is characterized by recurrent attacks of swelling with symptoms typically beginning in childhood. The introduction of targeted therapies for prevention and treatment of attacks has been of significant benefit to patients, including children, with HAE. However, the ideal of a safe, convenient therapy that prevents all attacks has not been realized. New approaches including ongoing inhibition of plasma kallikrein, and perhaps activated Factor XII, show promise in further improving the care of patients with HAE.
Get full access to this article
View all access options for this article.
References
1.
CicardiM, AbererW, BanerjiA, et al.Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy, 2014; 69:602–616.
BorkK, HardtJ, WitzkeG. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol, 2012; 130:692–697.
5.
PappalardoE, CicardiM, DuponchelC, et al.Frequent de novo mutations and exon deletions in the C1inhibitor gene of patients with angioedema. J Allergy Clin Immunol, 2000; 106:1147–1154.
6.
DavisAEIII. C1 inhibitor and hereditary angioneurotic edema. Ann Rev Immunol, 1988; 6:595–628.
7.
BanerjiA, SloaneDE, ShefferAL. Hereditary angioedema: a current state-of-the-art review, V: attenuated androgens for the treatment of hereditary angioedema. Ann Allergy Asthma Immunol, 2008; 100:S19–22.
8.
ShefferAL, AustenKF, RosenFS. Tranexamic acid therapy in hereditary angioneurotic edema. N Engl J Med, 1972; 287:452–454.
9.
FrankMM. Update on preventive therapy (prophylaxis) for hereditary angioedema. Allergy Asthma Proc, 2011; 32:17–21.
10.
PremattaM, GibbsJG, PrattEL, StoughtonTR, CraigTJ. Fresh frozen plasma for the treatment of hereditary angioedema. Ann Allergy Asthma Immunol, 2007; 98:383–388.
11.
ZurawBL, BussePJ, WhiteM, et al.Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med, 2010; 363:513–522.
12.
ZurawBL, KalfusI. Safety and efficacy of prophylactic nanofiltered C1-inhibitor in hereditary angioedema. Am J Med, 2012; 125:938.e1–e7.
13.
YooSM, KhanDA. Implantable venous access device associated complications in patients with hereditary angioedema. J Allergy Clin Immunol, 2013; 1:524–525.
14.
BabuYS, WilsonR, ZhangJ, CornproptsM, CollisP, SheridanW. A simple, sensitive assay to monitor plasma kallikrein inhibitory activity of BCX4161 in activated plasma. J Allergy Clin Immunol, 2014; 133:AB40.
15.
CollisP, CornpropstM, CollierJ, SheridanW. BCX4161, an oral kallikrein inhibitor: safety and pharmacokinetic results of a phase I study in health volunteers. J Allergy Clin Immunol, 2014; 133:AB39.
SextonD, KennistonJ, FaucetteR, et al.Comparison of plasma kallidrein inhibition by the monoclonal antibody inhibitor DX-2930 to endogenous C1-INH. J Allergy Clin Immunol, 2014; 133:AB30.
KaplanAP, JosephK. The bradykinin-forming cascade and its role in hereditary angioedema. Ann Allergy Asthma Immunol, 2010; 104:193–204.
22.
MaurerM, BaderM, BasM, et al.New topics in bradykinin research. Allergy, 2011; 66:1397–1406.
23.
JosephK, TholanikunnelBG, BygumA, GhebrehiwetB, KaplanAP. Factor XII-independent activation of the bradykinin-forming cascade: implications for the pathogenesis of hereditary angioedema types I and II. J Allergy Clin Immunol, 2013; 132:470–475.
24.
LarssonM, RayzmanV, NolteMW, et al.A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk. Sci Transl Med, 2014; 6:222ra17.
25.
RenneT, SchmaierAH, NickelKF, BlombackM, MaasC. In vivo roles of factor XII. Blood, 2012; 120:4296–4303.
26.
BirdJF, SmithPL, WangX. et al. Effects of plasma kallikrein deficiency on haemostasis and thrombosis in mice: murine ortholog of the Fletcher trait. Thromb Haemost, 2012; 107:1141–1150.
27.
SaitoH. Studies on Fletcher trait and Fitzgerald trait. A rare chance to disclose body's defense reaction against injury. Thromb Haemost, 2010; 104:867–874.
28.
RenneT, PozgajovaM, GrunerS, et al.Defective thrombus formation in mice lacking coagulation factor XII. J Exp Med, 2005; 202:271–281.
