Rasburicase-induced hemolytic anemia and methemoglobinemia: a systematic review of current reports

Since the FDA’s approval of rasburicase use for treatment of tumor lysis syndrome (TLS), multiple cases of rasburicase-induced methemoglobinemia and hemolytic anemia have been reported among patients with G6PD deficiency. This study aims to provide a systematic review of cases reporting such adverse reactions to rasburicase. A literature review of published cases in PubMed, Embase, Cochrane, and Web of Science was conducted. Descriptive studies reporting cases of rasburicase-induced methemoglobinemia and/or hemolytic anemia in English were analyzed and summarized in this study. Forty-three cases, including a case from our institution, were included in this study. Most cases (60.5%) received rasburicase for TLS treatment. Almost all patients (93.8%) were tested for G6PD after rasburicase administration. The median time to symptom onset was 24 h. The median methemoglobin level was 10%, peaking after a median of 24 h. The median hemoglobin nadir was 6.1 g/dL, and most patients (n = 32) required blood transfusion. Out of 39 cases with reported outcomes, 35 patients (89.7%) recovered, while four patients (three females and one male) died. The median time to recovery was 4.5 days while the median time to death was 8 days. Screening for G6PD deficiency among high-risk patients is important but not practical in acutely severe settings. When prior screening for G6PD deficiency is not feasible, close monitoring for methemoglobinemia and hemolytic anemia is recommended. Exchange transfusion is increasingly reported as a potentially successful therapeutic modality. Ascorbic acid may provide limited benefits. Methylene blue should be avoided as it may exacerbate hemolysis among these patients.