Methyldopa hemolytic anemia with

The answer is a. (Katzung, p 162.) Many drugs can cause an immunohemolytic anemia. Methyldopa may cause a positive Coombs test in as many as 20% of patients, along with hemolytic anemia. Other drugs with similar actions on red blood cells are penicillins, quinidine, procainamide, and sulfonamides. These form a stable or unstable hapten on the red cell surface, which induces an immune reaction I immunoglobulin G (IgG) antibodies] and leads to dissolution of the membrane. 

Autoantibodies to red blood cells and autoimmune hemolytic anemia have been observed in patients treated with numerous drugs, including procainamide, chlor-propaminde, captopril, cefalexin, penicillin, and methyldopa (Logue et al., 1970 Kleinman et al., 1984). Hydralazine- and procainamide-induced autoantibodies may also result in SLE. Approximately 20% of patients administered methyldopa for several weeks for the treatment of essential hypertension developed a dose-related titer and incidence of autoantibodies to erythrocytes, 1% of which presented with hemolytic anemia. Methlydopa does not appear to act as a hapten but appears to act by modifying erythrocyte surface antigens. IgG autoantibodies then develop against the modified erythrocytes. 

Other important adverse effects of methyldopa are development of a positive Coombs test (occurring in 10-20% of patients undergoing therapy for longer than 12 months), which sometimes makes cross-matching blood for transfusion difficult and rarely is associated with hemolytic anemia, as well as hepatitis and drug fever. Discontinuation of the drug usually results in prompt reversal of these abnormalities. 

Rapid exacerbation (1-21 days) or delayed (3-38 months) de novo appearance of immune hemolytic anemia has been reported after initiation of interferon alfa treatment in nine patients with lymphoproliferative disorders (220). However, this rare event was identified in only 1% of 581 patients receiving interferon alfa alone or as part of a chemotherapeutic regimen for chronic myelogenous leukemia (221). A mechanism close to that observed with alpha-methyldopa has been thought to be involved (208). The direct antiglobulin test was positive in 32% of 28 chronic myeloid leukemia patients after a median of 1 year of treatment with interferon alfa (222). 

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 (antiglobulin test) that is due to autoantibodies directed against the Rh antigen on erythrocytes. The development of a positive Coombs test is not necessarily an indication to stop treatment with methyldopa ... 

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. 

Methyldopa is the only antihypertensive drug associated with hemolytic anemia (usually preceded by a positive Coombs test). Hydralazine is also associated with autoimmune toxicity, but this takes the form of a lupus-like syndrome with butterfly facial rash, fever, joint and muscle pains, and antinuclear antibodies. The answer is (D). 

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... 

Worlledge SM, Carstairs KC, Dacie JV (1966) Autoimmune hemolytic anemia associated with alpha-methyldopa. Lancet 2 135... 

L-Dopa produces some of the same manifestations that a-methyldopa produces, including sensitization of red cells by antibody (with or without hemolytic anemia), drug fever, rash, and leukopenia, but all of these manifestations are rare. The hemolytic anemia produced by L-dopa is very rare. It appears to be of the autoimmune type, involving Rh determinants analogous to the much more common hemolytic anemia seen with a-methyldopa therapy (Worlledge 1973). L-Dopa has also been reported to produce an acute non-hemolytic anemia (Alkalay and Zi-POLi 1977). 

Hemolytic anemia is particularly associated with quinidine and methyldopa. The one case induced by quinidine (Freedman et al. 1956) was in a 69-year-old male with a past history of syphilis who developed signs of a purpuric eruption 4 days after starting treatment. The patient was treated with adrenocorticotrophic hormone and the red blood cell count had returned to normal by day 20. 

Hematologic Methyldopa-induced hemolytic anemia has been described in a young woman with hypertension [97" ]. 

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