Hemolysis, drug induced

Decreasing G-6-PDH activity in aging erythrocytes has been described (L4, L8). This finding becomes important in hereditary G-6-PDH deficiency, explaining the self-limiting effect of drug-induced hemolysis (B9, BIO, Bll). 

Since that time many investigations have been made to elucidate the mechanism of this drug-induced hemolysis [recently reviewed by Beutler (B7)]. The hemolytic symptoms were recognized to be hereditary and race linked. They were found to be due to lack of G-6-PDH activity in erythrocytes and other cellular blood compounds, and the mechanisms of the consequently appearing metabolic failures were emphasized. 

When in the past 10 years the mechanism of drug-induced hemolysis was studied, the implication of an enzyme system in the integrity-maintaining principle of the red cell became evident as did the probability of its interacting in the processes of maturation and senescence (B8, SI). 

Hypersensitivity is most frequently manifested by pruritus and skin rashes. Severe drug induced immune thrombocytopenia can occur. Hemolysis may occur in patients with G6PD deficiency. 

A. The patient will continue to be resistant to drug-induced hemolysis after six months or longer. 

Drug-induced hemolysis and muscular tissue damage can be reduced. 

Besides this hapten or penicillin-type of drug-induced hemolysis, a second less frequent mechanism, the so-called innocent bystander mechanism can occur (46,49,50). Penicillin-antibody complexes are only loosely bound to erythrocytes and activate complement, which can be detected on the erythrocyte surface with the complement antiglobulin test ( complement or nongamma type). This mechanism plays a part in immune hemolytic anemias due to various drugs other than penicillins. The hemolytic reaction can continue for weeks after withdrawal of penicillin, that is as long as sufficient penicillin-coated erythrocytes and specific antibodies remain in circulation. 

The severity of drug-induced immune hemolytic anemia is usually a function of the rate of hemolysis. Hemolytic anemia caused by drugs via the hapten/adsorption and autoimmune mechanisms tend to be slower in onset and mild to moderate in severity. Conversely, hemolysis prompted via the neoantigen mechanism (innocent bystander) phenomenon may have a sudden onset, lead to severe hemolysis, and result in renal failure. The treatment of drug-induced immune hemolytic anemia includes the removal of the offending agent and supportive care. Glucocorticoids are usually unnecessary, and practitioners have questioned their efficacy. ... 

Removal of the offending drug is the primary treatment for drug-induced oxidative hemolytic anemia. No other therapy is usually necessary, as most cases of drug-induced oxidative hemolytic anemia are mild in severity. Patients with these enzyme deficiencies should be advised to avoid medications capable of inducing the hemolysis. 

Kirkman HN. 1968. Glucose-6-phosphate dehydrogenase variants and drug-induced hemolysis. Ann NY Acad Sci 151 753-764. 

Uekama, K.. Irie, T., Sunada, M., Otagiri, M. and Tsubaki, K., Protective effects of cyclodextrins on drug-induced hemolysis in vitro, J. Pharm. Dyn., 4, 142-144 (1981). 

Gehrie E, Neff A, Giombor K, Harris N, SeegmiUer AC, Young PP. Profound piperacUUn-mediated drug-induced immune hemolysis in a patient with cystic fibrosis. Transfusion 2012 52 4r-5. 

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