An explanation for nonimmunologic adsorption of proteins onto red blood cells: Schiff's base reactions

During a phase I evaluation of diglycoaldehyde (INOX), an intravenous chemotherapeutic agent used to treat children with malignancies, all of eight patients tested developed a positive direct antiglobulin test (DAT) in vivo. The DAT became positive within one to seven days after the first administration of the drug and remained positive for up to 12 days following the last dose. The indirect antiglobulin tests were negative. None of the patients showed clinical or laboratory evidence of hemolysis at the time the DAT became positive or during follow-up. Eluates made from the red cells of two of the eight patients were both negative by indirect antihuman globulin testing. In vitro studies with INOX and glutaraldehyde, both dialdehyde compounds, showed nonimmunologic adsorption of protein onto red cells, probably by the condensation of aldehyde groups of these compounds to form Schiff's bases with amino acids of serum proteins and red cell membrane proteins. This reaction provides an explanation for the globulin detected on the red cells of patients treated with INOX.