ACTIVATION OF THE CONTACT SYSTEM AND FIBRINOLYSIS IN AUTOIMMUNE ACQUIRED ANGIOEDEMA - A RATIONALE FOR PROPHYLACTIC USE OF TRANEXAMIC ACID

C1-inhibitor deficiency results in bouts of mucocutaneous edema and ma y be inherited (hereditary angioedema) or acquired (acquired angioedem a [AAE]). The two forms have the same clinical picture but differ in t he response to treatment. Prophylaxis with antifibrinolytic agents pro duces better results in the acquired form than in the inherited form, in which androgen derivatives are more effective. It is hypothesized t hat 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 (aut oimmune AAE) by measuring the cleavage of high molecular weight kinino gen and the completes formed by plasmin and its inhibitor alpha(2)-ant iplasmin. We also measured complement parameters, autoantibody titer, and cleaved C1-inhibitor (relative molecular mass = 96,000), because a utoantibodies to C1-inhibitor are known to facilitate its cleavage by proteases. Plasma was obtained from patients in remission, during prop hylactic treatment with the antifibrinolytic agent tranexamic acid (2 to 4.5 gm/day) and also from two patients during acute attacks of edem a. Levels of cleaved high molecular weight kininogen and antiplasmin-p lasmin complexes in patients with AAE were both higher in basal condit ions, during treatment, and during acute attacks than those in normal subjects (p < 0.001). The cleaved inactive form of C1-inhibitor was al so present in all patients in all three conditions. Therapy with antif ibrinolytic agents reduced the frequency and intensity of symptoms wit hout significantly changing any of the biochemical parameters. Our dat a demonstrate that in patients with autoimmune AAE there is continuous activation of contact and fibrinolytic systems, which might be counte racted by antifibrinolytic agents, as indicated by the favorable effec ts of prophylactic treatment with tranexamic acid.