Mortality following rasburicase-induced methemoglobinemia

To report a case of mortality following rasburicase-induced methemoglobinemia.

A 62-year-old African American male with chronic lymphocytic leukemia and small lymphocytic lymphoma was admitted for tumor lysis syndrome and renal failure. He was treated with 2 doses of rasburicase, subsequently developed methemoglobinemia, and required intubation, multiple packed red blood cell (PRBC) transfusions, and 2 doses of methylene blue. A screen for glucose-6 phosphate dehydrogenase (G6PD) deficiency was negative. His course was complicated by hemolytic anemia, nosocomial pneumonia, Clostridium difficile infection, and septic shock. His methemoglobin concentrations normalized over several days; however, the patient eventually died on hospital day 16. An objective causality assessment revealed that the adverse drug reaction was probable.

Our case was similar to previously published cases, except that our patient died and his G6PD screen was negative. Although it was negative, it is likely that this was a false negative result because this blood was drawn shortly after PRBC transfusions and during active hemolysis. Both these are likely to cause false-negative results.

Methemoglobinemia is a rare adverse effect associated with the use of rasburicase and occurs most often in patients with G6PD deficiency. G6PD testing should not be ordered during active hemolysis or after blood transfusion because this may lead to false-negative results. Methylene blue should not be used as an antidote because it may worsen hemolytic anemia in patients with G6PD deficiency.