Abstract
The positive direct Coombs'' test was present only in those who had both azotemia and hypoalbuminemia. This finding can be accounted for by the high blood levels of cephalothin secondary to reduced renal excretion, decreased serum binding of cephalothin secondary to hypoalbuminemia, and further enhancement of serum levels by intravenously administered large doses which could cause this RBC abnormality. In these circumstances the RBCs may be coated with a cephalothin-globulin complex, which reacts with Coombs'' sera (anti-human globulin sera). It remains possible that the Coombs'' positive reactions may be related to cross reactivity with anti-penicillin antibody in the patients receiving cephalothin. There is, however, no evidence to support that this is an autoimmune state involving the RBCs as is found with the use of methyldopa. The Coombs'' positive reactions found with methyldopa have blood-group specificity, free autoantibody in the serum, definite evidence of hemolysis, and active eluates. The evidence does support the concept that the Coombs'' positive reactions associated with cephalothin are related to nonspecific binding to the RBC surface. It is not possible to relate the positive direct Coombs'' test to a hemolytic state. Investigations are presently under way to confirm this hypothesis.