Effect of G6PD Deficiency on Red Blood Cell Storage

Effect of Glucose-6-phosphate Dehydrogenase Deficiency on Donor Red Blood Cell Storage

The proposed study will determine whether G6PD-deficient RBCs store differently than normal RBCs under standard blood banking conditions. The investigators plan to screen a large number of healthy male volunteers for G6PD deficiency in order to identify 10 G6PD deficient and 30 matched normal individuals using a blood sample obtained from a finger-stick. The identified individuals will then be asked to donate a unit of blood that will be stored for up to 42 days and various tests will be performed on these units during storage. At 6 weeks of storage a portion of the unit will be radioactively labeled and re-infused into the volunteer. Blood samples will be drawn before, during, and after the infusion to measure how well or poorly the red blood cells survive after transfusion.

Study Overview

• Status: Completed
• Conditions: G6PD Deficiency
• Intervention / Treatment: Drug: Sodium Chromate Cr51

Detailed Description

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency, affecting approximately 400 million people world-wide. It manifests as red blood cell (RBC) destruction in response to oxidative stress, which can be precipitated by infection, and by the ingestion of certain medications and foods. The prevalence of G6PD deficiency varies among populations and is most commonly found in individuals from sub-Saharan Africa, the Mediterranean region, and south-east Asia. Although in most studies G6PD-deficient individuals have normal RBC survival at steady-state, this may vary based upon the G6PD variant present, and some individuals may have shortened RBC survival. While it is not routine practice to screen blood donors for G6PD deficiency, G6PD deficient donor RBCs may store more poorly than normal RBCs. In addition, the transfusion of stored G6PD-deficient RBCs may result in decreased RBC survival after transfusion compared to RBCs from normal donors.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
    • New York, New York, United States, 10065
      • New York Blood Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Healthy male volunteers will be screened for G6PD deficiency in order to identify 10 G6PD deficient and 30 matched normal individuals using a blood sample obtained from a finger-stick.

Description

Inclusion Criteria:

• Male
• Weight greater than 110 pounds
• Hemoglobin greater than 11.5 g/dL
• African (e.g., Afro-American, Afro-Caribbean, Sub-Saharan), Asian, Hispanic, Middle Eastern, or Mediterranean (e.g., Italian, Greek) based on mother's ancestry
• English speaking

Exclusion Criteria:

• Presence of hemoglobin variant
• Ineligible for donation based on the New York Blood Center donor autologous questionnaire
• Systolic blood pressure >180 or <90 mm Hg, diastolic blood pressure >100 or <50 mm Hg
• Heart rate <50 or >100
• Temperature >99.5°F prior to donation
• Temperature >100.4°F or subjective feeling of illness prior to transfusion (this criterion is to avoid concurrent illness affecting post-transfusion measurements)
• Positive results on standard blood donor infectious disease testing

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
G6PD-normal; Donated blood from G6PD-normal subjects	Drug: Sodium Chromate Cr51; Sodium Chromate Cr 51 will be used to perform a red blood cell recovered study 24 hours post-transfusion.; Other Names: Chromitope
G6PD-deficient; Donated blood from G6PD-deficient subjects	Drug: Sodium Chromate Cr51; Sodium Chromate Cr 51 will be used to perform a red blood cell recovered study 24 hours post-transfusion.; Other Names: Chromitope

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour post-transfusion red blood cell recovery	Percentage of radio-labeled red blood cells remaining 24 hours after infusion	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In vitro hemolysis rate	Percent hemolysis in the red blood cell unit in vitro	42 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of samples with metabolites detected	Metabolomics analysis: metabolites that are representative of major metabolic pathways will be measured in the red blood cells or supernatant during storage. Quantitative measurements will be performed using high performance liquid chromatography and mass spectrometry and the data obtained will be analyzed to detect correlations with the primary outcome measure of 24-hour post-transfusion red blood cell recovery.	Pre-donation to 42 days after donation

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: New York Blood Center
• Investigators: Principal Investigator: Richard O Francis, MD, PhD, Columbia University

Publications and helpful links

General Publications

• Francis RO, D'Alessandro A, Eisenberger A, Soffing M, Yeh R, Coronel E, Sheikh A, Rapido F, La Carpia F, Reisz JA, Gehrke S, Nemkov T, Thomas T, Schwartz J, Divgi C, Kessler D, Shaz BH, Ginzburg Y, Zimring JC, Spitalnik SL, Hod EA. Donor glucose-6-phosphate dehydrogenase deficiency decreases blood quality for transfusion. J Clin Invest. 2020 May 1;130(5):2270-2285. doi: 10.1172/JCI133530.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: September 5, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (Actual): September 9, 2019

Study Record Updates

• Last Update Posted (Actual): September 17, 2019
• Last Update Submitted That Met QC Criteria: September 16, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: transfusion; post-transfusion recovery
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Glucosephosphate Dehydrogenase Deficiency
• Other Study ID Numbers: AAAJ6862

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will share all individual study data results upon request once the study is published.
• IPD Sharing Time Frame: upon request once the study is published
• IPD Sharing Access Criteria: email study PI to request data
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No