COVID-19 and hydroxychloroquine side-effects: glucose 6-phosphate dehydrogenase deficiency (G6PD) and acute haemolytic anaemia

Chaney, Stephen G.; Basirat, Ahmad; McDermott, R.L.; Keenan, Natalie; Moloney, E

doi:10.1093/qjmed/hcaa267

Cited by 12 publications

(9 citation statements)

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“…Several factors can influence the clinical severity in patients with COVID-19. For example, in these patients, age is associated with elevated morbidity and mortality [ 15 ]. Aging not only affects the immune response, but also induces a pro-inflammatory state.…”

Section: Discussionmentioning

confidence: 99%

“…Chaney et al [ 15 ] detailed the case of a 57-year-old Nigerian male, who attended the emergency department with a 4 day history of fatigue, nausea, chills and anorexia. The man had a history of non-insulin dependent diabetes, hypertension, hypercholesterolaemia, glaucoma, gastro-oesophageal reflux disease and without known hematology history.…”

Section: Introductionmentioning

confidence: 99%

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Glucose-6-phosphate dehydrogenase deficiency and hydroxychloroquine in the COVID-19 era: a mini review

et al. 2021

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The coronavirus disease 2019 (COVID-19) is until today a global health emergency. In an immense effort, effective drugs against COVID-19 are searched and intensive researches on possible repurposing of antiviral agents are performed. Since chloroquine (CQ) and hydroxychloroquine (HCQ) have shown in vitro anti- COVID-19 activities, the potential effect of CQ/HCQ to treat and/or prevent COVID-19 infection has caused global attention. However, concern regarding possible hemolysis in G6PD-deficient COVID-19 patients exists and for this reason, the association between HCQ and G6PD deficiency (G6PDD) is back in the limelight. This study aims to answer the question raised by Mastroianni et al. “Hydroxychloroquine: Culprit or Innocent Bystander in G6PD-Deficient Patients with COVID-19?” , reporting all cases of HCQ in G6PD deficient COVID-19 patients published on PubMed (pubmed.ncbi.nlm.nih.gov), in addition to the Mastroianni’s patient. In our opinion, after an accurate revision of these cases and responding the question raised by Mastroianni et al., we believe that it is difficult to reach a final verdict about the definitive role of HCQ in these patients. The COVID-19 pandemic has reopened attention on HCQ use and G6PDD. G6PD status is extremely important in modulating the level of reactive oxygen species and many cellular immune responses such as enhanced production of the pro-inflammatory cytokine and inflammasome activation. Since these processes are involved in COVID-19 infection, acute hemolytic anemia, a severe complication of the G6PDD, can occur in these patients. In this context, the role of HCQ, usually effective, safe, and well tolerated in G6PD deficient patients, must be redefined in these patients with COVID-19.As consequence, answering the question: “ Hydroxychloroquine: Culprit or Innocent Bystander in G6PD-Deficient Patients with COVID-19?” , we state that it is risky to believe that HCQ may be an “innocent bystander” in G6PD-deficient COVID-19 patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glucose-6-phosphate dehydrogenase deficiency and hydroxychloroquine in the COVID-19 era: a mini review

et al. 2021

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“…Methemoglobinemia has been reported in other COVID-19 cases [22] and antimalarial drugs known to induce hemolysis in G6PD def , hydroxychloroquine and chloroquine, have been used to treat COVID-19. To date, seven case studies reported hydroxychloroquine/chloroquine triggered hemolysis in G6PD def COVID-19 patients [23][24][25][26][27].…”

Section: Effect Of G6pd Def In Nonhemolytic Disordersmentioning

confidence: 99%

Treatment strategies for glucose-6-phosphate dehydrogenase deficiency: past and future perspectives

Garcia

Koperniku

Ferreira

et al. 2021

Trends in Pharmacological Sciences

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Glucose-6-phosphate dehydrogenase (G6PD) maintains redox balance in a variety of cell types and is essential for erythrocyte resistance to oxidative stress. G6PD deficiency, caused by mutations in the G6PD gene, is present in ~400 million people worldwide, and can cause acute hemolytic anemia. Currently, there are no therapeutics for G6PD deficiency. We discuss the role of G6PD in hemolytic and nonhemolytic disorders, treatment strategies attempted over the years, and potential reasons for their failure. We also discuss potential pharmacological pathways, including glutathione (GSH) metabolism, compensatory NADPH production routes, transcriptional upregulation of the G6PD gene, highlighting potential drug targets. The needs and opportunities described here may motivate the development of a therapeutic for hematological and other chronic diseases associated with G6PD deficiency. G6PD deficiency as a hematological disorderGlucose-6-phosphate dehydrogenase (G6PD; see Glossary) regulates glycolytic flux through the pentose phosphate pathway (PPP) and plays a central role in redox homeostasis; it produces NADPH, an essential cofactor for glutathione (GSH) regeneration. G6PD is a major source of NADPH and loss of G6PD function is detrimental in erythrocytes; it causes G6PD deficiency (G6PD def ), a potentially hemolytic disorder [1]. HighlightsGlucose-6-phosphate dehydrogenase (G6PD) deficiency is better known as a hematological disorder. However, G6PD may play a role in other chronic disorders such as diabetes, cardiovascular disease, viral infectivity and complications, and neurodegeneration.

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“…The first case of severe hemolytic crisis was found in a seriously ill COVID-19 patient with G6PD deficiency following treatment with high doses of hydroxychloroquine [44]. Several other cases have subsequently been reported by others [45][46][47]. Nevertheless, Mastroianni et al [47] and Afra [48], concerning hydroxychloroquine use in G6PD-deficient patients, have indicated that it is difficult to assess the relationship between hydroxychloroquine and hemolysis in COVID-19 patients.…”

Section: Possible Reasons For Methemoglobinemia In Covid-19 Patientsmentioning

confidence: 99%

The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review

Scholkmann

Restin

Ferrari

et al. 2020

JCM

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Following the outbreak of a novel coronavirus (SARS-CoV-2) associated with pneumonia in China (Corona Virus Disease 2019, COVID-19) at the end of 2019, the world is currently facing a global pandemic of infections with SARS-CoV-2 and cases of COVID-19. Since severely ill patients often show elevated methemoglobin (MetHb) and carboxyhemoglobin (COHb) concentrations in their blood as a marker of disease severity, we aimed to summarize the currently available published study results (case reports and cross-sectional studies) on MetHb and COHb concentrations in the blood of COVID-19 patients. To this end, a systematic literature research was performed. For the case of MetHb, seven publications were identified (five case reports and two cross-sectional studies), and for the case of COHb, three studies were found (two cross-sectional studies and one case report). The findings reported in the publications show that an increase in MetHb and COHb can happen in COVID-19 patients, especially in critically ill ones, and that MetHb and COHb can increase to dangerously high levels during the course of the disease in some patients. The medications given to the patient and the patient’s glucose-6-phospate dehydrogenase (G6PD) status seem to be important factors determining the severity of the methemoglobinemia and carboxyhemoglobinemia. Therefore, G6PD status should be determined before medications such as hydroxychloroquine are administered. In conclusion, MetHb and COHb can be elevated in COVID-19 patients and should be checked routinely in order to provide adequate medical treatment as well as to avoid misinterpretation of fingertip pulse oximetry readings, which can be inaccurate and unreliable in case of elevated MetHb and COHb levels in the blood.

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COVID-19 and hydroxychloroquine side-effects: glucose 6-phosphate dehydrogenase deficiency (G6PD) and acute haemolytic anaemia

Cited by 12 publications

References 1 publication

Glucose-6-phosphate dehydrogenase deficiency and hydroxychloroquine in the COVID-19 era: a mini review

Glucose-6-phosphate dehydrogenase deficiency and hydroxychloroquine in the COVID-19 era: a mini review

Treatment strategies for glucose-6-phosphate dehydrogenase deficiency: past and future perspectives

The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review

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