Adverse effects of clinical intervention on the complement system

Adverse effects, due to activation of the complement (C) system and consequent generation of biologically active peptides, may occur during any form of extracorporeal processing of blood or plasma. Studies of the biocompatibility of dialyzer membranes have provided new insight into the mechanisms of C activation in extracorporeal circuits. The use of hemodialyzers, bypass oxygenators and on-line processing of plasma, by filtration or adsorption on columns, may all lead to activation of the alternative pathway of C and injurious reactions. The mechanisms by which drugs or drug metabolites interact with the C system, thereby inducing pseudoallergic reactions, have been only partly clarified. However, several drugs appear to interfere with the function of regulator proteins in the C system. Long-term administration of drugs that inhibit the covalent binding reaction of C3/C4 may contribute to development of drug-induced systemic lupus erythematosus in predisposed patients. Administration of high doses of immunoglobulins can cause anaphylactoid reactions which may involve C activation. Adverse reactions, seen after treatment with certain recombinant proteins, may also be associated with C activation.