Hemolysis methyldopa

Acute intravascular hemolysis has been described in a single case, and in this instance there were antibodies to hydrochlorothiazide methyldopa, which had been given concurrently, might have facilitated antibody formation (15). 

Overall, however, the reason that only some patients develop autoantibodies, and that only some of those have hemolytic disease, is not known. In an effort to explain why patients may have a positive result from a Coombs test and no hemolysis, Kelton demonstrated that methyldopa impairs the abihty of these patients to remove antibody-sensitized cells. In Coombs-positive patients receiving methyldopa, patients with impairment of the reticuloendothelial system could not clear the RBCs coated with autoantibodies from their bloodstream, and therefore hemolysis did not occur. Patients with hemolysis had no impairment of the reticuloendothelial system. Procainamide has also been reported to cause a positive result on the direct anti-human globulin test and hemolytic anemia. Other drugs that have been reported to cause autoimmune hemolytic anemia include levodopa, mefenamic acid, and diclofenac. ... 

Methyldopa can cause hemolytic anemia. At least 20% of patients who receive methyldopa for a year develop a positive Coombs test due to autoantibodies directed against the Rh antigen on erythrocytes. This does not necessitate drug discontinuation 1—5% of these patients will develop a hemolytic anemia that mandates prompt drug discontinuation. The Coombs test may remain positive for as long as a year cffter discontinuation of methyldopa, but the hemolytic anemia usually resolves within a matter of weeks. Severe hemolysis may be attenuated by treatment with glucocorticoids. Rarer adverse effects include leukopenia, thrombocytopenia, red cell aplasia, lupus erythematosus—like syndrome, lichenoid and granulomatous skin eruptions, myocarditis, retroperitoneal fibrosis, pancreatitis, diarrhea, and malabsorption. 

Some other drugs produce an autoimmune hemolytic anemia in which the antibodies are directed towards native antigens on the red cell surface, while the drug does not seem to function as a hapten in the reaction. This type of autoimmune hemolytic anemia has been described following treatment with levodopa, methyl-dopa, and mefenamic acid (Worrledge et al. 1966 Worrledge 1973). With a-methyldopa, clinically significant hemolysis develops in less than 1 % of individuals... 

There was concern, at one stage, about a number of reports demonstrating a positive antiglobulin test in patients who had been treated for more than 6 months with methyldopa. The incidence of this finding was established at about 5%-25% of treated patients (Gillies 1974 Corbett 1972 Seed at and Vawda 1972). It was expected that these patients would subsequently exhibit immune hemolysis and clinical anemia. This, however, proved not to be very few patients developed anemia (0.3%-5%) and then it was often precipitated by another factor such as infection. 

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