Treatment of episodes of hereditary angioedema with C1 inhibitor: serial assessment of observed abnormalities of the plasma bradykinin-forming pathway and fibrinolysis.
BACKGROUND
Hereditary angioedema (HAE) is typically the result of a deficiency of C1 inhibitor (C1-INH) with gene defects that lead to diminished plasma levels or the production of a dysfunctional protein. Replacement therapy with C1-INH has been shown to be effective in ameliorating episodes of swelling. We have reported elevated baseline levels of bradykinin, C4a, and plasmin-alpha2-antiplasmin complexes in the plasma of patients with HAE compared with the plasma of healthy controls. The production of factor XII fragment on in vitro activation of plasma with HAE has also been observed.


OBJECTIVE
To perform serial assessment of abnormalities of the bradykinin-forming pathway and fibrinolysis in patients with HAE after treatment of episodes of swelling with intravenous C1-INH.


METHODS
We obtained samples of plasma from 9 patients with HAE at a quiescent period (baseline), during an attack of swelling, and at 1, 4, and 12 hours after termination of an infusion of C1-INH. Factor XIIa, kallikrein, and plasmin were each measured by cleavage of synthetic substrates specific for each item.


RESULTS
Each enzyme was strikingly elevated at baseline compared with the levels in pooled healthy plasma, and there was a progressive decline of activity to normal for factor XIIa and plasmin. Kallikrein decreased in 7 of the 9 patients at 1 hour and then decreased in all patients. Bradykinin levels were elevated at the outset in all patients, increased prominently during an attack of swelling, decreased to baseline after 1 hour, and then decreased toward normal by 4 and 12 hours.


CONCLUSIONS
The plasma levels of factor XIIa, kallikrein, and bradykinin decreased when measured serially subsequent to the infusion of nanofiltered C1-INH.
Division of Rheumatology and Clinical Immunology, Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA. josephkusum@gmail.com
Kusumam
K
Joseph
Tracy E
TE
Tholanikunnel
Allen P
AP
Kaplan
D054179:Angioedemas, Hereditary / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D003167:Complement Activation / Q000187:drug effects; D050718:Complement C1 Inhibitor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D015934:Complement C4a / Q000378:metabolism; D015956:Factor XIIa / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007262:Infusions, Intravenous; D007610:Kallikreins / Q000097:blood / Q000494:pharmacology; D009154:Mutation
D050718:Complement C1 Inhibitor Protein; D015934:Complement C4a; D007610:Kallikreins; D015956:Factor XIIa; D005341:Fibrinolysin; D001920:Bradykinin