DICLOFENAC-INDUCED IMMUNE HEMOLYTIC-ANEMIA - SIMULTANEOUS OCCURRENCE OF RED-BLOOD-CELL AUTOANTIBODIES AND DRUG-DEPENDENT ANTIBODIES

During the last 5 years me hare identified a total of 17 patients (nin e females and eight males aged between 53 and 85 years) with immune ha emolytic anaemia related to diclofenac (a nonsteroidal anti-inflammato ry drug). AU patients developed acute intravascular haemolysis. Two pa tients died, and eight patients developed temporary renal failure that required haemodialysis. The direct antiglobulin test was positive wit h anti-IgG and anti-C3d in all cases, with anti-IgA in 4/10 cases test ed, and negative with anti-IgM. The indirect antiglobulin test was mod erately or weakly positive in 11 cases, and IgG autoantibodies could b e eluted from the red blood cells (RBCs) of all patients. Initially, t he diagnosis of autoimmune haemolytic anaemia of warm type was suggest ed in all cases. All patients had simultaneously developed autoantibod ies and drug-dependent antibodies. The majority of drug-dependent anti bodies (n=13) reacted with urine containing the drug and its metabolit es (ex vivo antigen), the native drug, and diclofenac-treated RBCs. Th e antibodies in the remaining four cases were detectable only in the p resence of ex vivo antigen. Diclofenac appears to bind only weakly to RBCs in the absence of the drug-dependent antibodies. We conclude that diclofenac forms neoantigens with RBCs that may stimulate the product ion of autoantibodies and drug-dependent antibodies. The resulting hae molytic syndrome is very similar to autoimmune haemolytic anaemia of w arm type.