Medical Literature - 1984

C1 inhibitor functional activities in hereditary angioedema plasma of patients under therapy with attenuated androgens

Spath PJ, Wuthrich B, Butler R 1/1984 Dermatologica

The effects of therapy with danazol or stanozolol on complement component C4 and on C1 inhibitor concentrations and functions in 6 patients suffering from the common form of hereditary angioedema are described. Whereas the mean C4 concentration was found within the normal range, the therapy with attenuated androgens resulted in a subnormal mean of C1 inhibitor concentration, but an almost normal mean of functional activity.


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Cold enhancement of blood coagulation: observations on the role of C1(-)-inhibitor

Donaldson VH. 1/1984 Acta Pathologica, Microbiologica, et Immunologica Scandinavica

Supplement ;284:41-47

The effect of incubation at 4 degrees C upon the one stage prothrombin times and the Thrombotest times of plasma from normal people, females taking oral contraceptive agents (O.C.A.’s) or in the third trimester of pregnancy, and patients with hereditary angioneurotic edema (H.A.N.E.) was measured to determine if enhancement of coagulant activity was regularly associated with reduced amounts of C1(-)- inhibitor (C1(-)-INH) in the plasma. Cold-enhanced coagulant activity was not always found in H.A.N.E. plasmas, markedly deficient in C1(-)- INH, and when found, the addition of purified C1(-)-INH to the plasma did not always prevent its development in vitro. Females taking O.C.A.’s regularly demonstrated cold-enhanced plasma coagulant activity in this series, as did pregnant females tested, as reported by others. The relation of C1(-)-INH levels in plasma to the cold-enhanced plasma coagulant activity was imperfect. In plasma obtained during pregnancy, but not exposed to 4 degrees C, C1(-)-INH levels were low despite minimal shortening of the Thrombotest time. Thus, these observations suggest that reduced levels of C1(-)-INH in plasma was not directly related to the tendency to generate enhanced coagulant activity at 4 degrees C. Other factors must be critical to the development of this activity, and the failure to block its development in C1(-)-INH deficient plasmas by adding purified C1(-)-INH at venesection suggests that events which initiate the development of this property may have occurred in vivo.

Not available online.

Inhibition of the complement activation by an adrenal androgen, dehydroepiandrosterone

Hidvegi T, Feher GK, Feher T, Koo E, Fust G. 1/1984 Complement


The effect of dehydroepiandrosterone (DEA), an adrenal androgen successfully used for preventing attacks in hereditary angioneurotic edema (HANE) patients was studied on the activation of classical and alternative complement pathway. The steroid inhibited both the spontaneous and immune activation of the classical complement pathway (CP), the former effect, however, was found to be more marked than the latter one. DEA exerted its inhibiting effect most probably by interfering with the internal activation of C1. Because DEA rendered HANE patients symptom free but induced only a slight increase in their serum C1-INH level, our present findings suggest that inhibition of CP activation may have a significance in the therapeutic effect of DEA and possibly of other androgens as well.

Not available online.

Interaction between C1-INA, coagulation, fibrinolysis and kinin system in hereditary angioneurotic edema (HANE) and urticaria

Bork K, Witzke G, Artmann K, Benes P, Bockers M, Kreuz W. 9/1984 Archives of Dermatological Research


The C1-inactivator plays an important rol.e not only in the initial phases of the complement system, but also in those of the coagulation, fibrinolysis and kinin systems. The present study was concerned with the reciprocal influence of decreased C1-inactivator levels in patients with hereditary angioneurotic edema (HANE, HAE). In 13 HANE-I patients there were significantly increased levels of the coagulation factors XII, XI, V, of plasminogen and of alpha 2-antiplasmin, while the factors IX and VII were decreased. Conversely, it emerged that in patients with markedly raised prephase factor levels, angioneurotic edema occurred in the presence of normal or only slightly decreased C1-inactivator levels. However, the ratio between factor XI and C1-INA activity was significantly higher than in normal and urticaria patients. Factor XII, HMWK, XI, VIII and V levels were significantly raised in 10 patients with frank chronic urticaria, while factor VII was lowered. Numerous other factors and inhibitors of the coagulation, fibrinolysis and kinin systems were, however, normal or showed no significant differences.

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Studies of four Japanese families with hereditary angioneurotic edema: simultaneous activation of plasma protease systems and exogenous triggering stimuli

Kodama J, Uchida K, Yoshimura S, Katayama Y, Kushiro H, Yutani C, et al. 11/1984 Blut


Forty-five relatives of 4 families with hereditary angioneurotic edema (HANE) were studied. Twenty-five, including 11 asymptomatic kindreds with the disposition, showed typical changes in complement system compatible with HANE. Follow-up study of HANE patients showed that, even in remission period, complement, coagulation and fibrinolytic systems can be activated. During edema attacks, moderate haemoconcentration and neutrophilia were encountered and kallikrein-kinin system was found to be also activated. Replacement therapy with C 1-inhibitor preparation for an edema attack revealed that clinical improvement paralleled the increase in blood levels of high molecular weight kininogen. Thus, HANE attack is considered to be elicited in kindreds with the hereditary disposition by activation of plasma protease systems, particularly by that of kallikrein-kinin system. On the other hand, exogenous triggers that can initiate activation of the protease systems can be classified into 2, neuro-humoral (sympathetic nerve response) and physico-chemical, categories. Hence, the edema attack of kindreds with the hereditary disposition can at least be modified by the biosynthesis of plasma factors and the individual susceptibility to the liberated catecholamines. These two different reaction processes are considered to be linked by the release of plasminogen activator and/or Hageman factor activating enzyme.

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The catabolism of C1(-)-inhibitor and the pathogenesis of hereditary angio-edema

Lachmann PJ, Rosen FS. 1/1984 Acta Pathologica, Microbiologica, et Immunologica Scandinavica

Supplement 1984;284:35-39

A sufficient explanation for the observations that HAE is a dominantly transmitted disease and that the hemizygotes have levels of the normal protein of only in the region of 15%-20% of normal can be given by proposing that a substantial proportion of the catabolism of C1(-)-esterase inhibitor involves the prior formation of a complex with one of the enzymes with which the inhibitor reacts. This part of the catabolism will be largely independent of inhibitor concentration, i.e. of zero order, and for this reason occurs similarly in normals and in hemizygotes. Estimates of the extent of this zero order metabolism can be obtained from turnover data with normal and dysfunctional C1(-)-inhibitor and the results are consistent with the observed levels. In the form of the disease associated with the dysfunction protein the dysfunctional protein makes up more than 85% of the total protein found for the same reason. The extent of the enzyme inhibitor complex dependent catabolism (RO) can be determined in vivo by simultaneous turnovers of dysfunctional and normal inhibitor and gives a measure of the extent of activation of this group of enzymes. The value of this technique in clinical practice is described elsewhere.

Not available online.

Funding for Canadian Hereditary Angioedema Network has been generously provided by unrestricted grants from:


CSL Behring


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