COMPLEMENT ACTIVATION BY HEPARIN-PROTAMINE COMPLEXES DURING CARDIOPULMONARY BYPASS - EFFECT OF C4A NULL ALLELE

Objectives: The first objective was to determine the effect of inherit ed differences in the classic pathway complement protein C4 on complem ent activation by heparin-protamine complexes in cardiac surgery, Spec ifically, we hypothesized that patients with heterozygous C4A null phe notype (A0BB), who have decreased amounts of C4A, may have increased c omplement activation because of reduced clearance of heparin-protamine complexes, The second objective was to determine whether heparin-prot amine-induced complement activation correlated with postoperative pulm onary shunt fractions, Methods: C4 typing was performed by agarose gel immunofixation and crossed immunoelectrophoresis. Complement activati on was measured by radioimmunoassay of C3a and C4a before cardiopulmon ary bypass, after bypass, and after protamine infusion, Shunt fraction s were calculated from blood gases, Results: Of the 79 patients, 18 ex pressed heterozygous C4A null allele (A0BB), 16 had heterozygous C4B n ull allele (AAB0), three had homozygous C4B null alleles (AA00), and t he rest expressed both C4A and C4B alleles (AABB). Patients with heter ozygous C4A null allele had significantly increased plasma levels of C 4a after protamine neutralization of heparin (C4a of 2862 +/- 375 ng/m l; mean +/- standard error of the mean) when compared with patients wi th normal expression of C4 alleles (AABB) (C4a of 1580 +/- 141 ng/ml) or heterozygous C4B null allele (C4a 1526 +/- 208 ng/ml), Pulmonary sh unt fractions obtained after the operation correlated with the classic pathway complement activation by heparin-protamine complexes, but not with alternative pathway complement activation during cardiopulmonary bypass, Conclusions: Patients with heterozygous C4A null phenotype ha ve increased complement activation by heparin-protamine complexes duri ng cardiac operations, possibly because of their defective clearance, The classic pathway complement activation by heparin-protamine interac tion correlates with postoperative pulmonary shunt fractions.