Recommended Citation
Fletcher N, Katwala K, Roy M. Rasburicase repercussions: methemoglobinemia and hemolytic anemia in an African American male with undiagnosed glucose-6-phosphate dehydrogenase deficiency. Presented at: American College of Physicians (ACP) Illinois Chapter 2025 Illinois Northern Resident & Student Day; November 12, 2025; Berwyn, IL.
Presentation Notes
Presented at: American College of Physicians (ACP) Illinois Chapter 2025 Illinois Northern Resident & Student Day; November 12, 2025; Berwyn, IL.
Award Information
Winner of Best in Presentation Award
Abstract
Introduction Rasburicase, a recombinant urate oxidase, effectively lowers nephrotoxic uric acid levels in tumor lysis syndrome (TLS). However, its use produces oxidative byproducts that can precipitate hemolysis and methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD). Although G6PD screening is recommended prior to use in high-risk populations, emergent presentations often preclude timely testing. We report a rare case of simultaneous rasburicase-induced methemoglobinemia and hemolytic anemia in a patient with previously undiagnosed G6PD deficiency. Case Presentation: A 74-year-old African American man with an indeterminate plasma cell dyscrasia and chronic kidney disease presented with 24 hours of abdominal pain, nausea, and emesis. Initial labs revealed elevated creatinine (2.81 mg/dL), BUN (47 mg/dL), uric acid (9.6 mg/dL) and phosphorus (6.3 mg/dL). Computed tomography (CT) of the abdomen and pelvis demonstrated omental carcinomatosis, lymphadenopathy, and distal esophagitis. Hematology consultation recommended rasburicase (3 mg IV) and concurrent G6PD testing for suspected TLS. Within 24 hours, the patient developed progressive asymptomatic hypoxemia requiring 6 L/min supplemental oxygen. Arterial blood gas revealed methemoglobinemia (6.8%) with a hemoglobin decline from 10.4 g/dL to 8.0 g/dL. Shortly after, hemolysis studies revealed indirect-predominant hyperbilirubinemia (2.4 mg/dL), elevated LDH (322 U/L), and evidence of iron overload. However, haptoglobin was initially preserved and repeat peripheral smears showed no schistocytes, Heinz bodies, or bite cells. Ascorbic acid (1,500 mg IV every 6 hours) was initiated and fluid resuscitation reduced due to pulmonary edema. Over the next 48 hours, oxygenation improved but hemoglobin declined to 6.3 g/dL requiring 4 total units of packed red blood cells. By days 3-4, LDH peaked at 532 U/L, haptoglobin fell to < 8 mg/dL, and initial quantitative G6PD assays yielded intermediate deficiency (3.6 and 4.2 U/g Hb, 30-40% of population median). Methemoglobin levels normalized, hemolysis stabilized, and the patient was discharged after 7 days without continued ascorbic acid. Discussion: Rasburicase catalyzes uric acid oxidation, generating hydrogen peroxide that can overwhelm antioxidant defenses in G6PD-deficient erythrocytes, causing methemoglobinemia and hemolytic anemia. Although these risks are well documented, concurrent presentation is uncommon (fewer than 50 cases) and is associated with significant (10%) mortality. In emergent TLS, rasburicase is often administered before G6PD results are available, underscoring the need for proactive monitoring for hypoxemia and evolving hemolysis. Early hemolytic markers may be discordant or lag behind clinical deterioration, complicating timely diagnosis. Standard methemoglobinemia therapies, such as methylene blue and hyperbaric oxygen, are contraindicated in G6PD deficiency because of their oxidative potential. In this case, high-dose intravenous ascorbic acid safely corrected methemoglobinemia without worsening hemolysis, supporting its role as an alternative when conventional therapies are unsuitable./ Conclusion: This case illustrates the dual risk of hemolysis and methemoglobinemia with rasburicase in unrecognized G6PD deficiency. It emphasizes the need for pre-treatment G6PD screening in at-risk populations, the potential for discordant early laboratory findings in hemolytic anemia, and the role of ascorbic acid as a therapeutic option when standard treatments are contraindicated
Type
Oral/Podium Presentation