Activation of the contact and complement systems in C1-inhibitor defic
iencies is thought to contribute to the pathogenesis of angioedema att
acks by releasing kinins. Trigger stimuli of attacks may also activate
coagulation. This is particularly important because experimental data
suggest that thrombin, the main enzyme of the coagulation cascade, in
creases vascular permeability and can thus influence edema formation.
We have studied 19 patients with hereditary angioedema (HAE) during re
mission, 5 HAE patients during acute attacks, and 6 patients with acqu
ired angioedema (AAE) during remission and during seven attacks, Thirt
y normal subjects, matched for sex and age, served as controls, Genera
tion of thrombin was measured by enzyme-linked immunosorbent assay (EL
ISA) as plasma levels of the prothrombin fragment 1 + 2 (F1 + 2); the
initiators of the tissue factor and contact coagulation pathways were
investigated by measuring plasma levels of activated factor VII (FVIIa
) coagulometrically and activated factor XII (FXIIa) by ELISA. Cleavag
e of high molecular weight kininogen (HK) was evaluated by immunoblott
ing analysis. F1 + 2 was slightly increased during remission and furth
er significantly increased during attacks in both HAE (P =.0115) and A
AE. FVIIa and FXIIa, normal during remission, increased strikingly dur
ing attacks in both HAE (P =.0022 and P =.0044) and AAE, During remiss
ion, cleaved HK was normal in HAE and high in AAE; during attacks it i
ncreased in HAE (P =.0008) and remained elevated in AAE. Our data indi
cate that in C1-inhibitor deficient patients there is increased genera
tion of thrombin during attacks, with signs of activation of both the
contact and tissue factor coagulation pathways. In conclusion, C1-inhi
bitor deficiency, whether hereditary or acquired, has demonstrable act
ivation of the coagulation and kinin-forming cascades during attacks a
nd that thrombin should be considered a possible contributing factor i
n the pathogenesis of edema in HAE and AAE. (C) 1997 by The American S
ociety of Hematology.