Medical Literature - 1994

Activation of the contact system and fibrinolysis in autoimmune acquired angioedema: a rationale for prophylactic use of tranexamic acid

Cugno M, Cicardi M, Agostoni A 5/1994 Journal of Allergy & Clinical Immunology

C1-inhibitor deficiency results in bouts of mucocutaneous edema and may be inherited (hereditary angioedema) or acquired (acquired angioedema [AAE]). The two forms have the same clinical picture but differ in the response to treatment. Prophylaxis with antifibrinolytic agents produces better results in the acquired form than in the inherited form, in which androgen derivatives are more effective. It is hypothesized that activation of the contact and fibrinolytic systems is involved in the pathogenesis of attacks. We evaluated these two systems in plasma from eight patients with AAE and anti-C1-inhibitor autoantibodies (autoimmune AAE) by measuring the cleavage of high molecular weight kininogen and the complexes formed by plasmin and its inhibitor alpha 2-antiplasmin. We also measured complement parameters, autoantibody titer, and cleaved C1-inhibitor (relative molecular mass = 96,000), because autoantibodies to C1-inhibitor are known to facilitate its cleavage by proteases. Plasma was obtained from patients in remission, during prophylactic treatment with the antifibrinolytic agent tranexamic acid (2 to 4.5 gm/day) and also from two patients during acute attacks of edema. Levels of cleaved high molecular weight kininogen and antiplasmin-plasmin complexes in patients with AAE were both higher in basal conditions, during treatment, and during acute attacks than those in normal subjects (p < 0.001). The cleaved inactive form of C1-inhibitor was also present in all patients in all three conditions. Therapy with antifibrinolytic agents reduced the frequency and intensity of symptoms without significantly changing any of the biochemical parameters.(ABSTRACT TRUNCATED AT 250 WORDS).


Available online at:

Administration of gamma interferon in human subjects decreases plasminogen activation and fibrinolysis without influencing C1 inhibitor

Gluszko P, Undas A, Amenta S, Szczeklik A, Schmaier AH 2/1994 Journal of Laboratory & Clinical Medicine

Recombinant gamma interferon (rHuIFN-gamma) has been recognized to increase mRNA and protein levels of C1 inhibitor (C1 INH) in various human cells. Further, when administered to patients with colon cancer, it increased plasma C1 INH levels. A prospective trial was initiated to determine whether rHuIFN-gamma could elevate plasma C1 INH levels in six normal volunteers and two patients with type I angioedema. After 1 month of observation of plasma C1 INH levels, rHuIFN-gamma was administered subcutaneously at 25 micrograms/M2 daily for 4 consecutive days. All healthy volunteers and patients experienced local erythema, headache, myalgias, and chills during the administration of rHuIFN-gamma. C1 INH, prekallikrein, high-molecular-weight kininogen, and factor XII levels in plasma were not influenced by the rHuIFN-gamma administration. One patient with hereditary angioedema (HAE) had an attack of angioedema 3 days after completion of rHuIFN-gamma therapy. During the attack, circulating cleaved high-molecular-weight kininogen, kallikrein-alpha 2-macroglobulin complexes, and an altered 50 kd form of kallikrein were detected in the patient’s plasma. Additional studies showed that rHuIFN-gamma treatment resulted in decreased total fibrinolytic activity. It was found that immediately after rHuIFN-gamma treatment, tissue plasminogen activator activity and antigen levels were not significantly decreased in volunteers. Plasminogen activator inhibitor levels rose significantly, but this activity was not due to plasminogen activator inhibitor-1 antigen, whose value significantly fell. These data suggest that rHuIFN-gamma may stimulate the expression of another plasminogen activator inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS).


Not available online.

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


CSL Behring


Contact Us

20 Carlton Street, Suite 123
Toronto, ON M5B 2H5
Tel: 416-585-3000

Patient Images

Patient Images

Copyright © 2024 CHAEN-RCAOH

All rights reserved.

Privacy Policy

Powered by Wild Apricot Membership Software