Case Report: Hemolysis in a G6PD-deficient patient, a dose-dependent effect of metformin

Glucose-6-phosphate deficiency is an X-linked genetic disorder, which predisposes erythrocytes to oxidative stress, resulting in hemolysis. It is the most common enzymatic deficiency, and typically affects African, Asian, Mediterranean, and Middle Eastern lineages. It can be induced by some medications, chemicals, and foods. Metformin is an uncommon drug to cause hemolysis in G6PD-deficient patients. \r\nWe report a case of a 52-year old African American male with G6PD-related hemolysis secondary to toxic metformin accumulation with acute kidney injury (AKI). The patient was a type-2 diabetic and was taking metformin (500mg twice daily) for three years. He presented to the ER with nausea, vomiting, and diarrhea for last three days with severe hemodynamic instability. Labs revealed hemoglobin 15mg/dl, white blood count 28 mm3/L, creatinine 10 mg/dl, blood urea nitrogen 100 mg/dl, bicarbonate 7 mEq/L, lactic acid 17 mg/dl, pH 6.8, pCO2 21mmHg, metformin 41 mcg/ml, albumin-globulin 41. Severe sepsis protocol was activated; IV fluids 30ml/kg bolus and antibiotics were given. CT abdomen revealed colitis. The patient was started on continuous renal replacement therapy. The next day, the patient’s hemoglobin dropped to 12.6 mg/dl. A hemolytic panel was unswerving with hemolysis and G6PD levels reported low at 1.72. The patient improved with antibiotics, but the hemolysis continued. Metformin toxicity induced hemolysis was suspected. The patient’s hemoglobin dropped to 6g/dl and he received blood transfusions. His hemoglobin started to improve with hemodialysis sessions, as metformin levels started to normalize, emphasizing the fact that patient was clearing metformin. \r\nUnlike most cases reported, in which hemolysis occurs within days to months of starting metformin, in our patient it occurred due to the cumulative effect of metformin because of the patient’s underlying AKI. This led us to propose that the hemolytic effect of metformin may not only be time-dependent but also dose-dependent.