The significance of complement in immunohematology

In vitro detection of red cell-bound complement can be important in the differential diagnosis of autoimmune and drug-induced immune hemolytic anemias; it can also be a sensitive test for the detection of complement-binding alloantibodies, e.g., in compatibility testing. Red cell-bound complement can be detected by the antiglobulin test if suitable antiglobulin sera (AGS) are utilized. In 1971, the Federal Standards for AGS were criticized because so-called broad spectrum AGS used routinely in blood banks were shown to often be deficient in anticomplement reactivity. In the new few years commercial regents changed with regard to the quantity and specificity of their anticomplement components. A great deal of controversy developed as to the true importance of detecting red cell-bound complement, the particular fragments of complement that should be detected, and the causes of nonspecific reactions that seemed to be occurring, especially with the increasing usage of new techniques utilizing low ionic strength media. When monospecific anti-IgG and anti-C3 became available commercially, the controversy regarding diagnostic testing was resolved as direct antiglobulin testing could be performed with these reagents rather than the broad spectrum reagents. Two main questions remained: how rare are alloantibodies that are only detectable by the anticomplement component of AGS? How clinically significant are such antibodies? The results of our 3-year study indicated that such antibodies (usually anti-Kidd) occurred with a incidence of 1/8000 sera tested. Some of these antibodies seemed capable of shortening the life span of transfused red cells, as determined by 51Cr survival studies; some showed negligible cell destruction. Severe transfusion reactions due to such antibodies would seem unlikely. Individual laboratories will have to balance the risk of missing some complement-dependent antibodies of possible clinical significance with the increased nonspecificity encountered in their own laboratory with AGS containing anticomplement.