A Rare Case of Acetaminophen Toxicity Causing Acute Hemolysis in G6PD Deficiency

INTRODUCTION: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the human enzyme defect causing hemolytic anemia after exposure to specific triggers. We present a case of acetaminophen toxicity inducing hemolysis in G6PD deficiency. CASE REPORT: A 46 year old African American male with history of alcohol abuse was admitted with acute pancreatitis. Initial labs showed total bilirubin 2.6, alkaline phosphatase 105 and aminotransferases AST/ALT 2000/4000. After 2 days there was acute elevation in his liver tests especially in AST 18000 and ALT 7000 with total bilirubin 9.9, Hb 11.4, INR 1.2. On detail history, patient told that prior to hospitalization, he was consuming acetaminophen (>6-7 g/day) for about a week. Patient was started on N-acetyl cysteine (NAC). Within 2 hours of starting NAC, patient became dyspneic. Chest X ray, arterial blood gas, CT head, doppler lower extremity and transthoracic ECHO was unremarkable. Patient was transferred to ICU and received high dose oxygen treatment but remained hypoxemic. Labs revealed drop in Hb to 8.7 and further to 5.6 with methemoglobulin 7.5%. Pt continued to have hyperbilirubinemia, mainly indirect bilirubin along with evidence of hemolysis. Patient had marked reticulocytosis, non-detectable haptoglobulin and elevated LDH. Peripheral blood smear revealed presence of bite cells. G6PD was normal as it reflects the young reticulocytes during acute phase. An enzymopathy with a drug-induced acute episode of hemolytic anemia was suspected. DISCUSSION: Acetaminophen is a safe antipyretic analgesic if maximum dose of 4 g/day is not exceeded, though higher doses >20 g/day may be fatal. It can be hepatotoxic even with daily doses of 2-6 g/day when associated with chronic alcoholism. It results in increased N-acetyl p benzoquninoneimine production causing depletion of reduced glutathione reserves. G6PD plays an important role in repletion of reduced-glutathione concentrations and minimizing oxidative damage hence low G6PD activity results in low reduced glutathione leading to acute hemolytic anemia. It is usually precipitated by an acute event (e.g., infection, drug reaction, ingestion of fava beans). Hemoglobin is converted to methemoglobin and precipitated as Heinz bodies. The spleen pinches off the Heinz body leaving a bite cell. Hence we concluded that acetaminophen overdose may act as an oxidative stress factor in G6PD deficiency by depleting reduced glutathione causing acute hemolysis.