C 1 ESTERASE INHIBITOR IS A HUMAN PLASMA-DERIVED, PURIFIED, PASTEURIZED, LYOPHILIZED CONCENTRATE OF C1 ESTERASE INHIBITOR PREPARED FROM LARGE POOLS OF HUMAN PLASMA FROM US DONORS. IT IS A SOLUBLE, SINGLE-CHAIN GLYCOPROTEIN CONTAINING 478 AMINO ACID RESIDUES.
C1 ESTERASE INHIBITOR IS A NORMAL CONSTITUENT OF HUMAN PLASMA AND BELONGS TO THE GROUP OF SERINE PROTEASE INHIBITORS (SERPINS) THAT INCLUDES ANTITHROMBIN III, ALPHA1-PROTEASE INHIBITOR, ALPHA2-ANTIPLASMIN, AND HEPARIN COFACTOR II. AS WITH THE OTHER INHIBITORS IN THIS GROUP, C1 ESTERASE INHIBITOR HAS AN IMPORTANT INHIBITING POTENTIAL ON SEVERAL OF THE MAJOR CASCADE SYSTEMS OF THE HUMAN BODY, INCLUDING THE COMPLEMENT SYSTEM, THE INTRINSIC COAGULATION (CONTACT) SYSTEM, THE FIBRINOLYTIC SYSTEM, AND THE COAGULATION CASCADE. REGULATION OF THESE SYSTEMS IS PERFORMED THROUGH THE FORMATION OF COMPLEXES BETWEEN THE PROTEINASE AND THE INHIBITOR, RESULTING IN INACTIVATION OF BOTH AND CONSUMPTION OF THE C1 ESTERASE INHIBITOR. C1 ESTERASE INHIBITOR, WHICH IS USUALLY ACTIVATED DURING THE INFLAMMATORY PROCESS, INACTIVATES ITS SUBSTRATE BY COVALENTLY BINDING TO THE REACTIVE SITE. C1 ESTERASE INHIBITOR IS THE ONLY KNOWN INHIBITOR FOR THE SUBCOMPONENT OF THE COMPLEMENT COMPONENT 1 (C1R), C1S, COAGULATION FACTOR XIIA, AND KALLIKREIN. ADDITIONALLY, C1 ESTERASE INHIBITOR IS THE MAIN INHIBITOR FOR COAGULATION FACTOR XIA OF THE INTRINSIC COAGULATION CASCADE.
HAE PATIENTS HAVE LOW LEVELS OF ENDOGENOUS OR FUNCTIONAL C1 ESTERASE INHIBITOR. ALTHOUGH THE EVENTS THAT INDUCE ATTACKS OF ANGIOEDEMA IN HAE PATIENTS ARE NOT WELL DEFINED, IT HAS BEEN POSTULATED THAT INCREASED VASCULAR PERMEABILITY AND THE CLINICAL MANIFESTATION OF HAE ATTACKS MAY BE PRIMARILY MEDIATED THROUGH CONTACT SYSTEM ACTIVATION. SUPPRESSION OF CONTACT SYSTEM ACTIVATION BY C1 ESTERASE INHIBITOR THROUGH THE INACTIVATION OF PLASMA KALLIKREIN AND FACTOR XIIA IS THOUGHT TO MODULATE THIS VASCULAR PERMEABILITY BY PREVENTING THE GENERATION OF BRADYKININ.5
ADMINISTRATION OF BERINERT TO PATIENTS WITH C1 ESTERASE INHIBITOR DEFICIENCY REPLACES THE MISSING OR MALFUNCTIONING PROTEIN IN PATIENTS.