Haemolytic anaemia methyldopa

Worlledge, S.M., Carstairs, K.C., and Dacie, J.V., Autoimmune haemolytic anaemia associated with alpha-methyldopa therapy, Lancet 288, 135, 1966. 

The Yellow Card Scheme was soon beginning to pay dividends. In early 1966, the YeUow Card Scheme had identified methyldopa as a cause of haemolytic anaemia and an appropriate advice was issued. Another success was the detection of a faulty batch of a particular product, which the manufacturer immediately withdrew, underlining the value of an efficient procedure for tracing a batch. During June 1967, the Committee distributed a leaflet on the use of aerosols in asthma. This was prompted by the death rate amongst asthmatic patients aged 5 to 34 years that had risen some 300% above the level in 1959-60 when such preparations were introduced. By September 1968, the rate had dropped to only 50% above that seen in 1959-60 despite sales having dropped only 20%. 

Type II reactions antibody-dependent cytotoxic type. The drug or metabolite combines with a protein in the body so that the body no longer recognises the protein as self, treats it as a foreign protein and forms antibodies (IgG, IgM) that combine with the antigen and activate complement which damages cells, e.g. penicillin- or methyldopa-induced haemolytic anaemia. 

In between 5 and 30% of cases treated with a-methyldopa for more than 6 months a positive Coombs test can be found. High dosage favours its development. In only 0.5—3% of these cases does a haemolytic anaemia develop at any time, the clinical picture often being precipitated by an intercurrent illness (3, 7 IF, 12, 18, 3V). In such cases, besides the positive Coombs test, typical warm reactive IgG antibodies are found which react with normal red cells in the absence of the drug. As in idiopathic IgG-induced warm reactive haemolysis the antibody is directed against the rhesus nucleus substance and the principal site of haemolysis is the spleen (38, 39, 40 ). 

Of-Methyldopa haemolytic anaemia may continue for a variable period of time after the use of the drug has been stopped. Treatment with corticosteroids is, however, rarely indicated. The Coombs test may remain positive for months, as may some of the other induced autoimmune phenomena (12 ). Granulocytopenia (18 ) as well as thrombocytopenia (3, 18, 42 =, 43 ) have been recorded in isolated instances. 

Djaldetti, M., Bessler, H., Lewinski, U. and Mandel, E M. (1974) Inhibition of uridine incorporation in proerythroblasts of patients with a-methyldopa induced haemolytic anaemia. Brit. J. Haematol, 27, 579. 

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