Drug Induced Hemolytic Anemia

Many drugs have been directly linked to immune hemolytic anemia. There are three types of reactions that can occur and result in hemolysis.

AUTOANTIBODY INDUCTION a-Methyldopa is the prototype drug of this reaction, and 10 to 20 percent of patients taking moderate-to-high doses will develop a positive direct Coombs' test. In this drug reaction, the RBCs become coated with an IgG that is directed against the Rh complex. Other drugs that can cause this are L-dopa, procainamide, ibuprofen, diclofenac, and thioridazine. Generally, it takes an extended period of drug exposure to develop the positive Coombs' test, and only a small number of those patients will develop severe hemolysis. The hemolysis ceases after the drug is stopped, but the Coombs' test may remain positive for a year or more.

HAPTEN-INDUCED IMMUNE HEMOLYSIS Penicillin is the classic drug associated with this reaction. Immune hemolysis can develop in patients receiving large intravenous doses of penicillin or penicillin-type antibiotics and usually starts 1 to 2 weeks after the therapy begins. The patient forms an antibody against the offending drug; then the antibody combines with the drug-RBC complex and causes hemolysis. Other drugs that can cause hemolysis by this mechanism include oxacillin, ampicillin, carbenicillin, and some cephalosporins. The hemolysis stops when the drug is discontinued.

INNOCENT BYSTANDER IMMUNE HEMOLYSIS Quinidine is the prototype drug for this reaction. Antibodies (IgG or IgM) are formed against the drug; then the drug-antibody complex binds to the RBC and hemolyzes it. Other drugs linked to this mechanism include quinine, isoniazid, sulfonamides, hydrochlorothiazide, antihistamines, insulin, chlorpromazine, tetracycline, acetaminophen, hydralazine, cephalosporins, fenoprofen, and sulindac. Even a small dose of the drug can cause hemolysis; however, these drugs are very commonly prescribed and the associated hemolysis is very rare.

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