Case Presentation: A 64-year-old woman with essential thrombocytosis presented with dyspnea. Clinical examination demonstrated a diagnosis of acute congestive heart failure that was confirmed by cardiomegaly on chest X-ray and an elevated brain natriuetic peptide. Chest CT excluded pulmonary embolism. She responded well to diuresis and her dyspnea resolved.
A peripheral smear revealed thrombocytosis with blasts, raising concern for acute myeloid leukemia with a blast crisis. A bone marrow biopsy was performed. Given the risk for hyper-uricemia secondary to tumor lysis, rasburicase was prescribed.
On the second hospital day, she developed refractory hypoxia initially thought to be due to worsening heart failure. This diagnosis was refuted by an arterial blood gas that revealed a PaO2 of 300 mmHg despite an arterial saturation of 80% which suggested an abnormal hemoglobin. Methemoglobinemia was suspected based upon recent rasburicase exposure. This was confirmed, methylene blue and ascorbic acid were administered, and she was transferred to the ICU for ventilatory support.
On the following day, there was an acute drop in hemoglobin concentration – attributed to hemolytic anemia. G6PD deficiency was confirmed as the cause, likely precipitated by the administration of the methylene blue. Attempts were made to establish an exchange transfusion, but her condition deteriorated rapidly, resulting in a cardiac arrest and death.
Discussion: Tumor lysis is one of the more common complications in patients with cancer, especially for those patients with a high tumor burden. Given the frequency with which these patients are admitted to the hospital, the prophylactic administration of agents such as rasburicase and allopurinol is often done without consideration for potential side effects from these medications.
Methemoglobinemia occurs in less than one percent of patients who take rasburicase; the incidence is the same in patients with G6PD deficiency. The treatment for methemoglobinemia is methylene blue. In the setting of methylene blue administration, patients with G6PD deficiency are highly susceptible to acute hemolytic anemia.
An FDA warning recommends screening populations with high incidences of G6PD deficiencies prior to treatment with methylene blue. The practical reality, however, is that when methemoglobinemia presents, prompt initiation of therapy is required which precludes time for screening. The only way to prevent this scenario is awareness of the patient’s G6PD status prior to beginning methylene blue therapy.
Exchange transfusion is the only alternative when a patient requires methylene blue for methemoglobinemia but is succumbing to hemolytic anemia secondary to G6PD deficiency.
Conclusions: Hospitalists frequently encounter patients with myeloproliferative disorders. While oncologists are primarily responsible for the administration of chemotherapy, the hospitalist is tasked with the vigilance for and management of common side-effects of these agents.