Quality and Biologic Characteristics of Red Blood Concentrates Obtained From Individuals With Elevated Ferritin.

Iron overload in hereditary hemochromatosis (HH) is treated by phlebotomy. It is unclear, if individuals with hyperferritinemia due to hereditary hemochromatosis or to secondary causes are suitable as blood donors. The study investigates hemolysis and several other quality parameters of red blood cell concentrates (RBC) obtained from 80 individual with ferritin >500 ng/mL - due to hereditary hemochromatosis or secondary - and 20 healthy blood donors as control.

Study Overview

• Status: Enrolling by invitation
• Conditions: Hereditary Hemochromatosis; Hyperferritinemia
• Intervention / Treatment: Procedure: Venipuncture

Detailed Description

Iron overload in hereditary hemochromatosis is treated by phlebotomy. In Switzerland and in many other coutries, these individuals are not accepted for blood donation until ferritin values and phlebotomy intervals are in the normal range.

Individual with secondary hyperferritinemia, e. g. related to metabolic syndrome, are accepted as blood donors according to their clinical situation.

It is unclear if the quality of blood products issued from individuals with hyperferritinemia due to hereditary hemochromatosis or to secondary causes is comparable with the quality of those issued from healthy blood donors, and if their characteristics comply with the international standards.

The study investigates the hemolysis rate and several other quality parameters in RBC obtained from 80 individual with ferritin >500 ng/mL - due to hereditary hemochromatosis or secondary - and 20 healthy blood donors as control. For this purpose, whole blood donations are manufactured according to the standard processes applied in the blood bank. Several standard quality parameters as well as biologic, rheologic, and oxydative stress-related variables are measured and compared, both with the current regulations and with those of the control group.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland
    • Blutspendedienst SRK beider Basel
  • Berne, Switzerland, 3008
    • Interregionale Blutspende SRK

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age:18-75 years
• Body weight > 50 Kg
• Haemoglobin ≥ 135 g/l (males), ≥ 125 g/l (females)
• In subjects of the HH and non-HH group: ferritin values >500 ng/ml, which must have been measured in the last three months before the inclusion in the study (either at the Blood Donation service or elsewhere), not followed by a blood donation or a phlebotomy
• In subjects of the HH group: genetic test demonstrating the presence of p.C282Y homozygous or p.C282Y/p.H63D compound heterozygous HFE-gene mutation
• In subjects of the control group: ferritin values < 300 ng/ml (males) or < 200 ng/ml (females)
• Written informed consent to the participation in the study

Exclusion Criteria:

• Inadequate vein access for whole blood collection
• Body weight < 50 kg
• Chronic viral infection (hepatitis B or C, HIV)
• Previous acute coronary heart disease
• Previous or current history of epilepsy
• Other severe conditions that could significantly increase the phlebotomy risk, based on individual medical evaluation
• No informed consent
• Pregnancy (according to the information on the standard blood donor questionnaire)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hereditary hemochromatosis; Individual with ferritin >500 ng/mL and documented homozygous or compound heterozygous HFE-gen mutation.	Procedure: Venipuncture; Bloodletting of 450 mL, followed by separation of the whole blood in 2 blood components: 1 red blood cell concentrate and 1 plasma. Measurement of the outcomes in the red blood cell concentrate.
Experimental: secondary hyperferritinemia; Individual with ferritin >500 ng/mL, not fulfilling the criteria for hereditary hemochromatosis.	Procedure: Venipuncture; Bloodletting of 450 mL, followed by separation of the whole blood in 2 blood components: 1 red blood cell concentrate and 1 plasma. Measurement of the outcomes in the red blood cell concentrate.
Other: healthy blood donor with normal ferritin value.; Healthy comparator.	Procedure: Venipuncture; Bloodletting of 450 mL, followed by separation of the whole blood in 2 blood components: 1 red blood cell concentrate and 1 plasma. Measurement of the outcomes in the red blood cell concentrate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemolysis rate vs regulatory standards.	To verify that the hemolysis rate in % at the end of storage (day 42) of RBC from individuals with elevated ferritin is within the current accepted European standard of 0.8%.	After 42 days of storage

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemolysis hyperferritinemia vs controls end of storage.	Comparison of haemolysis rate in % at day 42 in RBC from individuals with elevated ferritin of any cause and those with normal ferritin levels.	After 42 days of storage
Hemolysis hereditary hemochromatosis (HH) vs secondary hyperferritinemia entd of storage.	Comparisons of hemolysis rate in % at day 42 in RBC from individuals with HH and those with secondary hyperferritinemia.	After 42 days of storage
Hemolysis hyperferritinemia vs controls day 1.	Comparisons of hemolysis rate in % at day 1 in RBC from individuals with hyperferritinemia and those with normal ferritin.	After 42 days of storage

Collaborators and Investigators

• Sponsor: Interregionale Blutspende SRK

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2023
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: February 14, 2023
• First Posted (Estimate): February 23, 2023

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 14, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Iron Metabolism Disorders; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Iron Overload; Hemochromatosis; Hemosiderosis; Hyperferritinemia
• Other Study ID Numbers: 2022-00274

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No