Cl-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-Cl-inhibitor autoantibodies (autoimmune AAE) by measuring the cleavage of high molecular weight kininogen and the complexes formed by plasmin and its inhibitor α2-antiplasmin. We also measured complement parameters, autoantibody titer, and cleaved Cl-inhibitor (relative molecular mass = 96,000), because autoantibodies to Cl-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 Cl-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. Our data demonstrate that in patients with autoimmune AAE there is continuous activation of contact and fibrinolytic systems, which might be counteracted by antifibrinolytic agents, as indicated by the favorable effects of prophylactic treatment with tranexamic acid.
- Acquired angioedema
- high molecular weight kininogen
- tranexamic acid
ASJC Scopus subject areas
- Immunology and Allergy