LAUSR

Dear Editor, We read with interest the recent report by Montgomery and Booth, who described a case of methemoglobinemia in a 50-year-old, G6PD-deficient African American man with newly diagnosed T-cell lymphoblastic leukemia being treated with rasburicase for tumor lysis syndrome. Due to ongoing hemolysis and refractory hypoxia, the authors performed a one blood volume erythrocytapheresis with a 45% decrease in methemoglobin (14.6%–8%). Surprisingly, the patient continued to be hypoxic with subjective dyspnea, bilateral pleural effusions, and mildly elevated methemoglobin levels (7.5–11%) for 36 h post-exchange. We would like to share our experience in a nearly identical patient several years ago, in whom we observed an immediate improvement in symptoms following erythrocytapheresis. The patient was a 64 kg, 15-year-old African-American male with a 2-week history of fever, Bell’s palsy, lymphadenopathy, nausea, and abdominal pain due to new T-cell lymphoblastic leukemia. His initial laboratories showed a mildly elevated WBC count (11.6 K/lL, range 13.7–17) with 40% circulating blasts, anemia (hemoglobin 11.4 g/dL), elevated lactate dehydrogenase ([LDH] 8375 IU/L, range 120–240 IU/L), hyperuricemia (29.5 mg/dL, range 3.5–7.8), and acute renal failure (creatinine 4.8 mg/dL, range, 8–20). While in the emergency room, he received 6 mg rasburicase for tumor lysis syndrome. Within 3 h of receiving rasburicase, he became hypoxic with O2 saturation 70-80% despite escalating O2 supplementation, accompanied by falling hemoglobin and methemoglobinemia (16%, range 0–1.5%). The patient was transfused 1 unit RBC and given a 25% test dose of methylene blue with no clinical improvement, worsening anemia, tachypnea (21–27 breaths/minute), and ongoing methemoglobinemia. Within 12 h of admission, the patient required intubation with O2 saturations5 60% on 100% FiO2, methemoglobin5 23%, lactate5 5 mmol/L (range, 0.4–2.2), hemoglobin5 7.9 g/dL, LDH5 12,699 IU/L, and acidosis (pH5 7.2). The patient subsequently underwent emergent erythrocytapheresis for methemoglobinemia and presumed G6PD-deficiency. The procedure was performed on a COBE Spectra at a whole blood: anticoagulant ratio of 7:1, 30% fraction cell remaining, an end hematocrit of 30%, and 8 units group O RBC (2693 mL) for replacement. The patient had a brisk clinical response to erythrocytapheresis with O2 saturations >90% by the end of the procedure. He was extubated approximately 4 h post-procedure with a methemoglobin5 5% and O2 saturation5 95% on 2 L supplemental oxygen. By day 3, the patient had normal O2 saturation on room air and a methemoglobin5 2.3%. Subsequent testing confirmed that the patient was G6PD-deficient. This is the fifth report of refractory methemoglobinemia treated by either whole-blood exchange or erythrocytapheresis,1–4 and the third case following rasburicase administration in G6PD-deficient patients. Like carbon monoxide poisoning, methemoglobinemia causes a left-shift in the O2 dissociation curve, leading to a progressive and refractory hypoxia that is exacerbated and amplified in the setting of anemia. Patients with symptomatic methemoglobinemia are typically treated with supplemental oxygen, RBC transfusion, and methylene blue, which helps restore glutathione levels. In G6PDdeficient patients, however, methylene blue can independently precipitate hemolysis and methemoglobinemia. This case shows a prompt improvement in oxygenation with erythrocytapheresis in the setting of methemoglobinemia and G6PDdeficiency, in whom methylene blue is contra-indicated.