Rasburicase-induced methemoglobinemia: The eyes do not see what the mind does not know

Abstract

Rasburicase is indicated for the prevention and treatment of tumor lysis syndrome which can be a potentially life-threatening emergency. The drug has oxidizing potential and as an adverse effect, it can convert the ferrous form of iron in erythrocytes to its ferric form resulting in the formation of methemoglobin which makes the heme component incapable of carrying oxygen. Patients with glucose-6-phosphate dehydrogenase enzyme deficiency are at high risk of methemoglobinemia from oxidizing agents. Symptoms of methemoglobinemia range from none to life-threatening hypoxemia, cyanosis and respiratory compromise. Treatment is indicated at levels above 20% and at lower levels if the patient is significantly anemic. We present a case of a 60-year-old male with diffuse large B cell lymphoma at high risk of tumor lysis syndrome. Rasburicase was administered to prevent renal failure and further rise in uric acid. Twenty-four hours later, a bedside pulse oximetry showed an oxygen saturation ranging from 60 to 65% with minimal cyanosis. Co-oximetry revealed a methemoglobin level of 9.8%. Methylene blue was administered and the methemoglobin level decreased to 2.6%. However, the patient developed hemolysis several hours later, likely secondary to rasburicase and methylene blue, requiring transfusion support. We discuss this potentially fatal and initially asymptomatic adverse effect of rasburicase along with diagnostic and treatment considerations, and review the cases described in the current literature.

Rasburicase Induced Severe Hemolysis and Methemoglobinemia in a Caucasian Patient Complicated by Acute Renal Failure and ARDS

“…He also had a drop of around 5.5mg/dl of hemoglobin in 36 hours which also gave us another clue that the patient has a complication from the rasburicase. Screening patients at high risk of glucose-6phosphate dehydrogenase (G6PD) deficiency, individuals of African and Mediterranean descent, is recommended prior to initiation of rasburicase even if it is not done frequently in practice [2,3,7,9,10]. We were aware that methylene blue is contraindicated in patients with G6PD deficiency but considering patient being Caucasian of European descent and low risk for it and his deteriorating respiratory condition, it was decided to offer the treatment for him.…”

Rasburicase induced severe hemolysis and methemoglobinemia in a Caucasian patient complicated by acute renal failure and ARDS

“…He also had a drop of around 5.5mg/dl of hemoglobin in 36 hours which also gave us another clue that the patient has a complication from the rasburicase. Screening patients at high risk of glucose-6-phosphate dehydrogenase (G6PD) deficiency, individuals of African and Mediterranean descent, is recommended prior to initiation of rasburicase even if it is not done frequently in practice [2,3,7,9,10]. We were aware that methylene blue is contraindicated in patients with G6PD deficiency but considering patient being Caucasian of European descent and low risk for it and his deteriorating respiratory condition, it was decided to offer the treatment for him.…”

“…We were aware that methylene blue is contraindicated in patients with G6PD deficiency but considering patient being Caucasian of European descent and low risk for it and his deteriorating respiratory condition, it was decided to offer the treatment for him. On the other hand, it is also suggested that a high index of suspicion of G6PD deficiency is also crucial in a patient who develops methemoglobinemia or hemolytic anemia following rasburicase therapy, irrespective of ethnic origin [1,2,10,12,13].…”

Update on the prevention and treatment of tumor lysis syndrome

“…First, patients must be tested for catalase and glucose-6-phosphate dehydrogenase deficiency prior to treatment with rasburicase, as those populations are at risk of life-threatening rasburicase-induced methemoglobinemia. [125][126][127][128] Second, in the setting of rasburicase use, urinary alkalinization is contraindicated due to association with acute renal failure. 129 Third, rasburicase remains active ex vivo, so when monitoring serum UA levels in patients on rasburicase, all blood samples must immediately be placed on ice before being sent to the laboratory for UA quantification.…”