Generation of plasmin during acute attacks of hereditary angioedema.
Hereditary angioedema is caused by a genetic deficiency of C1-inhibitor, a serine protease inhibitor that regulates activation of complement, contact, and fibrinolytic systems. Symptoms (bouts of subcutaneous and mucous swelling) depend on the release of a vasoactive mediator, probably through activation of these three systems. We studied the interrelationship among complement, contact, and fibrinolytic activation in 23 patients with hereditary angiodema, 18 during remission and five during an attack, by measuring plasma levels of C1-C1 inhibitor, factor XIIa-C1 inhibitor, kallikrein-C1 inhibitor, and plasmin-alpha 2-antiplasmin complexes, tissue plasminogen activator, and urokinase plasminogen activator. In addition, cleavage of high-molecular weight kininogen was detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis and quantified by densitometry. During remission, plasma levels of C1-C1 inhibitor complexes were elevated (p = 0.0002), whereas the other parameters were within the normal range. During acute attacks, not only plasma levels of C1-C1 inhibitor complexes but also those of plasmin-alpha 2-antiplasmin complexes (P = 0.0009) and cleaved high-molecular weight kininogen were elevated. A positive correlation between plasmin-alpha 2-antiplasmin complexes and cleaved high-molecular weight kininogen was observed (r = 0.75, p < 0.001). This article presents the first in vivo evidence that supports the concept that release of vasoactive mediators in hereditary angiodema attacks is associated with the activation of the fibrinolytic system.
Cugno
M
M
Istituto di Medicina Interna, Ospedale Policlinico, Università di Milano, Italy.
Hack
C E
CE
de Boer
J P
JP
Eerenberg
A J
AJ
Agostoni
A
A
Cicardi
M
M
D000208:Acute Disease; D000328:Adult; D000799:Angioedema / Q000097:blood* / Q000235:genetics; D003165:Complement System Proteins / Q000032:analysis; D005260:Female; D005341:Fibrinolysin / Q000096:biosynthesis*; D005342:Fibrinolysis; D006801:Humans; D007704:Kininogens / Q000032:analysis / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight
D007704:Kininogens; D003165:Complement System Proteins; D005341:Fibrinolysin