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      Can Hydroxychloroquine Cause G6PD-Related Hemolysis? A Case Study

      case-report

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          Abstract

          During the pandemic of COVID-19, which started in December 2019, hydroxychloroquine, the drug which was first introduced as antimalarial medication, was widely used to treat this new viral infection, and it was reported in the literature as a safe drug for use in patients with G6PD deficiency; here, we report a 64-year-old male who was started on hydroxychloroquine as treatment for COVID-19 that led to hemolysis, and further investigation showed that the patient is deficient for glucose-6-phosphate dehydrogenase.

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          The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis.

          Ella T Nkhoma, Charles Poole, Vani Vannappagari … (2015)
          Glucose-6-phosphate deficiency is the most prevalent enzyme deficiency, with an estimated 400 million people affected worldwide. This inherited deficiency causes neonatal hyperbilirubinemia and chronic hemolytic anemia. Although most affected individuals are asymptomatic, exposure to oxidative stressors such as certain drugs or infection, can elicit acute hemolysis. To characterize the global prevalence of G6PD deficiency, we conducted a systematic review of the G6PD deficiency literature, drawing studies from various databases, including MEDLINE/Pubmed and Biosis. Selected studies included cross-sectional and longitudinal studies published between 1960 and 2008. Additionally, meta-analytic procedures were employed to assess the degree of heterogeneity amongst prevalence estimates and, where appropriate, pool them. The searches yielded a total of 280 prevalence estimates, corresponding to 88 countries. The highest prevalence rates were reported among Sub-Saharan African countries, even after adjusting for assessment method. Meta-analysis revealed a high degree of heterogeneity for regional and global prevalence estimates. This heterogeneity in reported estimates appeared to be due to differences in G6PD deficiency assessment and diagnostic procedures. The magnitude and variation in global, regional, and country-level prevalence rates of G6PD deficiency are of public health import, particularly in planning programs to improve neonatal health and in the distribution of various medications, especially antimalarial drugs, as G6PD deficiency is most prevalent in malaria-endemic areas.
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            Glucose-6-phosphate dehydrogenase deficiency and antimalarial drug development.

            Stephan Duparc, Ernest Beutler, (2007)
            Glucose-6-phosphate dehydrogenase (G6PD) deficiency is relatively common in populations exposed to malaria. This deficiency appears to provide some protection from this infection, but it can also cause hemolysis after administration of some antimalarial drugs, especially primaquine. The risk of drug-induced G6PD deficiency-related hemolysis depends on a number of factors including the G6PD variant, the drug and drug dosage schedule, patient status, and disease factors. Although a great deal is known about the molecular biology of G6PD, determining the potential for drug-induced hemolysis in the clinical setting is still challenging. This report discusses the potential strategies for assessing drug-induced G6PD deficiency-related hemolytic risk preclinically and in early clinical trials. Additionally, the issues important for conducting larger clinical trials in populations in which G6PD deficiency is prevalent are examined, with a particular focus on antimalarial drug development.
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              G6PD: population genetics and clinical manifestations.

              E Beutler (1996)
              The glucose-6-phosphate dehydrogenase (G6PD) gene is X-linked. There are numerous mutations that cause a deficiency of this enzyme in erythrocytes. G6PD deficiency can produce anemia, both when drugs are administered and under the stress induced by infection. Functionally severe variants cause hereditary non-spherocytic hemolytic anemia, i.e. anemia even in the absence of stress. Neonatal jaundice occurs in G6PD deficiency, but it is likely that it is largely due to impairment of liver function, rather than to hemolysis. It has been suggested that there are clinical manifestations of G6PD deficiency that are related to other tissues, but the existence of these is not well documented. Some mutations that produce G6PD deficiency in red cells exist at polymorphic frequencies. Individuals with such mutations seem to have enjoyed a selective advantage because of resistance to falciparum malaria. Different mutations, each characteristic of certain populations, are found, and have been characterized at the deoxyribonucleic acid (DNA) level. G6PD A-(202A376G) is the most common African mutation. G6PD Mediterranean(563T) is found in Southern Europe, the Middle East and in the Indian subcontinent. Several other mutations are common in Asia. Genetic variability of G6PD has played an important role in the understanding of a variety of developmental processes.
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                Author and article information

                Journal
                Journal ID (publisher-id): DMJ
                Title: Dubai Medical Journal
                Publisher: S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH–4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                ISSN (Electronic): 2571-726X
                Publication date (Electronic): 17 November 2020
                Pages: 1-3
                Affiliations
                [1 ] aMedical Education Department, Hamad Medical Corporation/Hamad General Hospital, Doha, Qatar
                [2 ] bHematology Department, Hamad Medical Corporation/National Center for Cancer Care & Research, Doha, Qatar
                Author notes
                *Khaldun Obeidat, Medical Education, Hamad Medical Corporation, Al Rayan Street, Doha 3050 (Qatar), dr.khaldun.obeidat@ 123456gmail.com
                Article
                Publisher ID: dmj-0001
                DOI: 10.1159/000511688
                PMC ID: 7705928
                SO-VID: 211b5fc1-9767-4dec-9e3d-4b388994c14e
                Copyright © Copyright © 2020 by S. Karger AG, Basel
                License:

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 11 July 2020
                Date accepted : 16 September 2020
                Page count
                Figures: 1, References: 10, Pages: 3
                Categories
                Subject: Case Report

                Keywords: hydroxychloroquine,covid-19,glucose-6-phosphate dehydrogenase,sars-cov-2,hemolysis
                Data availability:
                Keywords: hydroxychloroquine, covid-19, glucose-6-phosphate dehydrogenase, sars-cov-2, hemolysis

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