[Positive direct Coombs' test in acute leukemias and other hemoblastoses: relation to clavulanic acid-containing antibiotics?]

Alerted by a high incidence of positive autologous controls in pretransfusion compatibility testing for patients with acute leukemia, we retrospectively analysed 59 cases of severe hemoblastoses undergoing myelosuppressive treatment. Seventeen (29%) of these patients had a positive direct antiglobulin test (DAT) with the following characteristics: the test was of the IgG and/or C3d type in all but two cases, which reacted with polyvalent antiglobulin sera only; the reaction was very weak throughout; very high concentrations of monospecific sera were needed to elicit positive reactions; free antibodies were never detected in the patients' serum; the eluates of the patients' red cells were non-reactive against a very large panel of test erythrocytes. All these criteria suggested a non-immunologic absorption of proteins under the influence of drugs such as cephalosporins and clavulanic acid. Timenten (ticarcillin and clavulanic acid) was found to be the only common drug which had been administered to the majority of the patients with a positive DAT: 15 of the 17 patients with a positive DAT (88%) had received Timenten against 19 of 42 patients (45%) with negative DAT. 44% of all the patients receiving Timenten thus had a positive DAT, whereas only 8% of the patients without this drug reacted in this way. These data document the role of clavulanic acid in the development of a positive DAT. The literature and our experience show that this kind of unspecific binding of proteins to the red cell membrane is not associated with increased hemolysis. Knowledge of the phenomenon, however, is important for differential diagnosis of anemias and interpretation of difficulties arising during pretransfusional compatibility testing.