Brief Report: Hydroxychloroquine does not induce hemolytic anemia or organ damage in a "humanized" G6PD A- mouse model

Benjamin E. Zuchelkowski; Ling Wang; Sebastien Gingras; Qinzi Xu; Minying Yang; Darrell Triulzi; Grier P. Page; Victor R. Gordeuk; Daniel B. Kim-Shapiro; Janet S. Lee; Mark T. Gladwin

doi:10.1371/journal.pone.0240266

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Brief Report: Hydroxychloroquine does not induce hemolytic anemia or organ damage in a "humanized" G6PD A- mouse model

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Brief Report: Hydroxychloroquine does not induce hemolytic anemia or organ damage in a "humanized" G6PD A- mouse model

Benjamin E. Zuchelkowski, Ling Wang, Sebastien Gingras, Qinzi Xu, Minying Yang, Darrell Triulzi, Grier P. Page, Victor R. Gordeuk, Daniel B. Kim-Shapiro, Janet S. Lee, …

PloS one, Vol.15(10), pp.e0240266-e0240266

10/02/2020

DOI: 10.1371/journal.pone.0240266

PMCID: PMC7531777

PMID: 33007039

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Abstract

Background Hydroxychloroquine (HCQ) is widely used in the treatment of malaria, rheumatologic disease such as lupus, and most recently, COVID-19. These uses raise concerns about its safe use in the setting of glucose-6-phosphate dehydrogenase (G6PD) deficiency, especially as 11% of African American men carry the G6PD A- variant. However, limited data exist regarding the safety of HCQ in this population. Study design and methods Recently, we created a novel "humanized" mouse model containing the G6PD deficiency A- variant (Val68Met) using CRISPR technology. We tested the effects of high-dose HCQ administration over 5 days on hemolysis in our novel G6PD A- mice. In addition to standard hematologic parameters including plasma hemoglobin, erythrocyte methemoglobin, and reticulocytes, hepatic and renal function were assessed after HCQ. Results Residual erythrocyte G6PD activity in G6PD A- mice was similar to 6% compared to wild-type (WT) littermates. Importantly, we found no evidence of clinically significant intravascular hemolysis, methemoglobinemia, or organ damage in response to high-dose HCQ. Conclusions Though the effects of high doses over prolonged periods was not assessed, this study provides early, novel safety data of the use of HCQ in the setting of G6PD deficiency secondary to G6PD A-. In addition to novel safety data for HCQ, to our knowledge, we are the first to present the creation of a "humanized" murine model of G6PD deficiency.

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Title: Subtitle: Brief Report: Hydroxychloroquine does not induce hemolytic anemia or organ damage in a "humanized" G6PD A- mouse model
Creators: Benjamin E. Zuchelkowski - University of Pittsburgh
Ling Wang - University of Pittsburgh
Sebastien Gingras - University of Pittsburgh
Qinzi Xu - Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, Pittsburgh, PA, United States of America.
Minying Yang - Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, Pittsburgh, PA, United States of America.
Darrell Triulzi - University of Pittsburgh
Grier P. Page - RTI International
Victor R. Gordeuk - University of Illinois at Chicago
Daniel B. Kim-Shapiro - Wake Forest University
Janet S. Lee - University of Pittsburgh
Mark T. Gladwin - University of Pittsburgh
Resource Type: Journal article
Publication Details: PloS one, Vol.15(10), pp.e0240266-e0240266
DOI: 10.1371/journal.pone.0240266
PMID: 33007039
PMCID: PMC7531777
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library Science
Number of pages: 7
Grant note: 5R01HL098032 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Vitalant Blood Sciences Foundation Hemophilia Center of Western Pennsylvania
Language: English
Date published: 10/02/2020
Academic Unit: Orthopedics and Rehabilitation
Record Identifier: 9984304684202771

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