Rasburicase Induced Hemolytic Anemia
Rasburicase is a recombinant uric acid oxidase that is used to rapidly reduce plasma uric acid levels in patients with hyperuricemia due to tumor lysis syndrome. Rasburicase converts urate to allantoin and hydrogen preroxide. Allantoin is water soluble and rapidly excreted by the kidney.
Although rasburicase is generally well tolerated, hemolytic anemia may occur in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is the most common red cell enzyme deficiency, affecting approximately 400 million people worldwide. It is an X-linked inherited disorder, most commonly affecting persons of African, Southeast Asian, and Mediterranean ethnicity with a gene frequency of 5% to 25%. In the United States, African American males are most commonly affected, with a prevalence of approximately 10%. Given the risks of hemolysis, screening of patients at high risk of G6PD deficiency has been recommended prior to the administration of rasburicase. Although G6PD testing is recommended prior to rasburicase administration, it is often not practical because of disease acuity.
Patients with G6PD deficiency are unable to convert glucose-6-phosphate into 6-phosphogluconolactone. Consequently, they are unable to metabolize the hydrogen peroxide which is produced when rasburicase oxidizes uric acid to allantoin. Hemoglobin is oxidized to methemoglobin and the accumulation of denatured hemoglobin causes hemolysis.
Patients may develop hypoxia, hyperkalemia and methemoglobinemia within 24 hours of administration. Examination of a peripheral blood smear will often show bite cells, helmet cells , blister cells and increased nucleated red blood cells. A methylene blue-stained peripheral smear will show Heinz bodies. Other laboratory findings include decreased hemoglobin, increased bilirubin, increased lactate dehydrogenase, decreased haptoglobin and hemoglobinuria.
References
Ferguson D and Kovach AE. Rasburicase-induced hemolytic anemia in previously undiagnosed G6PD deficiency. Blood 2018;132:673.
Nguyen AP and Ness GL. Hemolytic anemia following rasburicase administration: A review of published reports. J Pediatr Pharmacol Ther. 2014;19:310-16.
