Metformin-Induced Hemolytic Anemia

Kırkız, Serap; Yaralı, Neşe; Bilir, Özlem; Tunç, Bahattin

doi:10.1159/000356149

Cited by 17 publications

(13 citation statements)

References 7 publications

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“…Nonetheless, its use should be avoided in patients with severe renal and/or liver dysfunction. As for all drug treatments, physicians should be vigilant for the occurrence of rare side effects [ 34 , 35 , 36 , 37 ]. It is possible that the high toxicity of phenformin compared to metformin is related to the much greater affinity of phenformin (>50) for mitochondrial membranes and subsequent suppression of oxidative phosphorylation, although other mechanisms may also contribute [ 38 , 39 ].…”

Section: The Pharmacokinetics Of Metforminmentioning

confidence: 99%

Metformin: An Old Drug for the Treatment of Diabetes but a New Drug for the Protection of the Endothelium

Kinaan¹,

Ding²,

Triggle³

2015

Med Princ Pract

1,105

124

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The anti-diabetic and oral hypoglycaemic agent metformin, first used clinically in 1958, is today the first choice or ‘gold standard' drug for the treatment of type 2 diabetes and polycystic ovary disease. Of particular importance for the treatment of diabetes, metformin affords protection against diabetes-induced vascular disease. In addition, retrospective analyses suggest that treatment with metformin provides therapeutic benefits to patients with several forms of cancer. Despite almost 60 years of clinical use, the precise cellular mode(s) of action of metformin remains controversial. A direct or indirect role of adenosine monophosphate (AMP)-activated protein kinase (AMPK), the fuel gauge of the cell, has been inferred in many studies, with evidence that activation of AMPK may result from a mild inhibitory effect of metformin on mitochondrial complex 1, which in turn would raise AMP and activate AMPK. Discrepancies, however, between the concentrations of metformin used in in vitro studies versus therapeutic levels suggest that caution should be applied before extending inferences derived from cell-based studies to therapeutic benefits seen in patients. Conceivably, the effects, or some of them, may be at least partially independent of AMPK and/or mitochondrial respiration and reflect a direct effect of either metformin or a minor and, as yet, unidentified putative metabolite of metformin on a target protein(s)/signalling cascade. In this review, we critically evaluate the data from studies that have investigated the pharmacokinetic properties and the cellular and clinical basis for the oral hypoglycaemic, insulin-sensitising and vascular protective effects of metformin.

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Section: The Pharmacokinetics Of Metforminmentioning

confidence: 99%

Metformin: An Old Drug for the Treatment of Diabetes but a New Drug for the Protection of the Endothelium

Kinaan¹,

Ding²,

Triggle³

2015

Med Princ Pract

1,105

124

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“…A literature search was performed concerning the side effects of metformin and its connection with G6PD related hemolytic anemia. Metformin-induced hemolysis in G6PD patients is very rare and, to the best of our knowledge, only seven cases are reported in the literature [3][4][5][6][7][8][9][10] . Discontinuation of metformin resulted in the recovery of most cases, except one which had a fatal outcome (hemoglobin drop of 11.4mg/dl) regardless of metformin discontinuation 5 .…”

Section: Discussionmentioning

confidence: 99%

“…Patients with North African, Jewish descent had low G6PD activity with a negative anti-globin test, showing the connection between G6PD-induced hemolytic anemia secondary to the use of metformin as seen in two cases prior in addition to our case 4,6 . Other cases with positive antiglobulin test 3,5,7 increased the possibility of drug-induced hemolytic anemia secondary to antibody formation. Supportive treatment was given in all cases, except in the case of metformin poisoning 9 and our case, which required continuous renal replacement therapy and blood transfusion.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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. We 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. Unlike 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.

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“…Here, the drug attaches covalently to proteins on the erythrocyte membrane. Hemolytic reaction in vivo necessitates the presence of the drug and stops shortly after discontinuation [7].…”

Section: Dear Editor;mentioning

confidence: 99%