Should Blood Donors Be Routinely Screened for Glucose-6-Phosphate Dehydrogenase Deficiency? A Systematic Review of Clinical Studies Focusing on Patients Transfused With Glucose-6-Phosphate Dehydrogenase–Deficient Red Cells

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Abstract

The risk factors associated with the use of glucose-6-phosphate dehydrogenase (G6PD)–deficient blood in transfusion have not yet been well established. Therefore, the aim of this review was to evaluate whether whole blood from healthy G6PD-deficient donors is safe to use for transfusion. The study undertook a systematic review of English articles indexed in COCHRANE, MEDLINE, EMBASE, and CINHAL, with no date restriction up to March 2013, as well as those included in articles' reference lists and those included in Google Scholar. Inclusion criteria required that studies be randomized controlled trials, case controls, case reports, or prospective clinical series. Data were extracted following the Preferred Reporting Items for Systematic Reviews using a previously piloted form, which included fields for study design, population under study, sample size, study results, limitations, conclusions, and recommendations. The initial search identified 663 potentially relevant articles, of which only 13 studies met the inclusion criteria. The reported effects of G6PD-deficient transfused blood on neonates and children appear to be more deleterious than effects reported on adult patients. In most cases, the rise of total serum bilirubin was abnormal in infants transfused with G6PD-deficient blood from 6 hours up to 60 hours after transfusion. All studies on neonates and children, except one, recommended a routine screening for G6PD deficiency for this at-risk subpopulation because their immature hepatic function potentially makes them less able to handle any excess bilirubin load. It is difficult to make firm clinical conclusions and recommendations given the equivocal results, the lack of standardized evaluation methods to categorize red blood cell units as G6PD deficient (some of which are questionable), and the limited methodological quality and low quality of evidence. Notwithstanding these limitations, based on our review of the available literature, there is little to suggest that G6PD-deficient individuals should be excluded from donating red blood cells, although transfusions of such blood may potentially have negative impacts on premature neonates or patients who need repeated transfusions, and thus, for this group, screening for G6PD deficiency may be appropriate.

Section snippets

Protocol

This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (Fig 1 and Table 1) (http://prisma-statement.org/).

Eligibility Criteria: Inclusion and Exclusion Criteria

The focus of the review is on articles that examine clinical settings involving individuals receiving whole blood or packed RBCs from healthy G6PD-deficient individuals. The studies eligible for inclusion, therefore, included randomized controlled trials, case controls, case reports, or prospective clinical series that

Level of Evidence and Data Quality

The strength of evidence reported within the 13 identified studies was then assessed using the hierarchy of evidence framework, focusing on the appropriateness and feasibility of the study, which is also reported in Table 3 [19]. The following grading was used, as proposed by Evans [19]: excellent, multicenter studies; good, randomized controlled trials, observational studies, and interpretative studies; fair, descriptive studies, before and after design, and focus groups; and poor, expert

Study Characteristics and Samples

Although the initial search identified 663 potentially relevant articles, only 13 studies met the inclusion criteria. Studies reviewed were from various countries such as Brazil (n = 1), China (n = 1), Iran (n = 2), India (n = 4), Israel (n = 2), Nigeria (n = 1), and United States (n = 2) and regions such as Americas (n = 3), Asia (n = 5), and Africa/Middle East (n = 5). Five of the research articles focused on the effects of G6PD-deficient blood transfused to adult patients, and 8 focused on the effects of

Studies Among Neonates and Children

Zekavat et al [21] undertook a clinical series study of 114 patients aged from 4 to 15 years admitted to a hospital for G6PD deficiency hemolytic anemia after broad bean ingestion. The authors examined the residual blood in transfusion blood bags, and of the 114 transfusion blood bags used across patients, 100 had G6PD-sufficient RBCs (ie, normal) and 14 had G6PD-deficient red cells. The hemoglobin level was checked after 6 hours. In both groups, hemoglobin levels rose significantly before and

Studies Among Adults

Raciti et al [29] assessed the consequences of transfusing RBC units that are G6PD deficient and contain hemoglobin variants on a 27-year-old woman with SCD. The woman attended an outpatient apheresis unit at a tertiary care medical center for scheduled RBC exchange transfusions (RBCEx) for secondary prophylaxis of stroke (blood type: O + with negative red cell antibody screen). She had been receiving RBCEx every 1.5 to 2 months as an outpatient as part of her medical treatment plan, and her last

Discussion

From the review of these 13 studies, it appears that results differed depending on the study population. The effects of G6PD-deficient transfused blood on neonates and children appear to have been more deleterious than those on adult patients. In most cases, the rise of TSB was abnormal in infants transfused with G6PD-deficient blood from 6 hours up to 60 hours after transfusion. Generally, there was also an increase in the median duration of phototherapy and a need for repeat exchange

Conclusion

Globally, most blood services do not currently consider G6PD deficiency systematically as an issue associated with sourcing blood donations. However, the potentially negative effects associated with transfused G6PD-deficient blood on recipients have received considerable comment and recommendations but, unfortunately, have been infrequently studied directly. Over a period of 40 years, only 13 studies have been identified as relevant to the subject. However, there is no conclusive evidence on

Acknowledgments

A/Prof. Andre Renzaho is supported by an ARC Future Fellowship. We would like to acknowledge Associate Professor Erica Wood, a Transfusion Medicine Specialist, and Head of the Transfusion Research Unit at the Department of Epidemiology and Preventive Medicine, for commenting on the draft.

References (42)

  • M.K. Alabdulaali et al.

    Prevalence of glucose-6-phosphate dehydrogenase deficiency and sickle cell trait among blood donors in Riyadh

    Asian J Transfus Sci

    (2010)
  • C.D. Padilla et al.

    Newborn screening in the Asia Pacific region

    J Inherit Metab Dis

    (2007)
  • World Health Organization. Blood Donor Selection: Guidelines on Assessing Donor Suitability for Blood Donation 2012....
  • M.R. Deyhim et al.

    An evaluation of glucose-6-phosphatedehyrogenase (G6PD) deficiency in blood donors in Mazandaran province, in Iran by spot test and enzymatic methods

    Vox Sang

    (2011)
  • W. Riley et al.

    The United States' potential blood donor pool: estimating the prevalence of donor-exclusion factors on the pool of potential donors

    Transfusion

    (2007)
  • M. Kaplan et al.

    Exchange transfusion for neonatal hyperbilirubinemia with glucose-6-phosphate–deficient blood

    Pediatr Health

    (2009)
  • Australian Institute of Health and Welfare

    Australia's Health 2012

    (2012)
  • Australian Department of Health and Ageing, Analysis of Cost Drivers and Trends in the Blood Sector Options to Manage...
  • Brown University, Division of Biology and Medicine
  • P.S. Swerdlow

    Red cell exchange in sickle cell disease

    Hematology Am Soc Hematol Educ Program

    (2006)
  • K.E. King et al.

    Delayed hemolytic transfusion reactions in sickle cell disease: simultaneous destruction of recipients' red cells

    Transfusion

    (1997)
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    Eliette Husser conducted the initial search and data extraction and performed the data analysis and summary as well as drafting the first manuscript. Andre Renzaho supervised the conduct of the study. He independently verified the data extraction, provided intellectual input into the data analysis and summary and the drafting of the article, and critically reviewed the manuscript. All authors have approved its submission.

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