Previous: Introduction: Plasma cascade systems with emphasis on the role of C1-inhibitor-Fibrinolysis

Introduction

Role of C1-inhibitor in the cascade systems; a summary
It is increasingly recognised that the historically and didactically motivated division of proteolytic plasma components into four cascade systems; complement, kallikrein-kinin, coagulation and fibrinolysis does not reflect the dynamic interplay in the body (232,240-242). Patients lacking C1-INH further illustrates the close relationship between the cascades, the advantage of a broad view on the cascades, and finally, the pivotal role of this inhibitor.

Fig. 12. The blocking of proteases by normal amounts of C1-inhibitor. Abbreviations, see Fig. 13.

In the event of limited C1-INH an extensive activation take place.

Fig. 13. Limited amounts of C1-inhibitor permits extensive activation across traditional cascade divisions. Kal = kallikrein. T-PA = tissue type plasminogen activator. Plmg = plasminogen. BK = bradykinin. HK = high molecular weight kininogen. PK = prekallikrein.

As a result of low C1-INH, complement factors in the early classical complement pathway are cleaved. This may cause autoimmune disease, affect the function of C4BP and thereby possibly the Protein C/S system of coagulation. The activation of the kallikrein-kinin system yields bradykinin leading to enhanced capillary permeability and contraction of smooth muscle. Fibrinolysis is enhanced. By the administration of tranexamic acid, which restricts the effects of plasminogen and plasmin, patients with C1-INH deficiency may enjoy a respite from attacks. Obviously, the cascade systems must be looked upon as a whole to further understand how this intricate interplay affects pathophysiology and cause symptoms in hereditary angioedema.

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