The Effect of Blood Donation on Hematological and Iron Indices and Detection of Autologous Blood Transfusion

Study Overview
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Brief Summary
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Blood donations is a essential and crucial in the clinic. Normal biological variation of relevant biomarkers and hormones before the donation of 450 mL whole blood as well as the expected alterations in systemic levels of plasma iron indices and RBC measures up to 4 weeks after donation in healthy, non-anemic, young men and women is investigated Likewise, the possibilities for detecting autologous blood transfusion is investigated.

Detailed Description
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Blood donations is a essential and crucial in the clinic. A whole blood donation results in the loss of 450-525 mL whole blood in eight to ten minutes and is known to reduce body iron stores with 200-265 mg iron depending on the donor's age, hematocrit and sex and accounts for 25% of average tissue iron stores in men and up to 75% in women.In the present study, the investigators aimed at thoroughly evaluate normal biological variation of relevant biomarkers and hormones before the donation of 450 mL whole blood as well as the expected alterations in systemic levels of plasma iron indices and red blood cell measures up to 4 weeks after donation in healthy, non-anemic, young men and women Likewise, doping in sport is a major problem concerning both the health of the athletes and the integrity of sports. Despite major improvements in anti-doping work in recent years, it is still impossible to test for all existing and future doping strategies, such as manipulation with blood oxygen carrying capacity. A well-known doping strategy is autologous blood transfusion (ABT), and at present, the detection of ABT is a challenge for anti-doping authorities. The hypotheses for this study are that 1) ret% and abnormal blood profile score (ABPS) have higher sensitivity to micro-dose ABT compared to current variables in the Athlete Biological Passport (ABP); 2) The plasma concentration of hepcidin and erythroferrone (ERFE) is sensitive to micro-dose ABT; 3) Gender-specific variations in hematologic variables affect the interpretation of the athlete's biological passport.

Official Title
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The Effect of Blood Donation on Hematological and Iron Indices and Detection of Autologous Blood Transfusion

Conditions
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Healthy

Intervention / Treatment
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* Procedure: Blood donation and blood transfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relative maximum oxygen uptake (VO2-max) of at least 55 ml O2/min/kg for male participants and 50 ml O2/min/kg for female participants Exclusion Criteria: Age Insufficient fitness level Blood donation 3 months prior to enrollment Altitude exposure 2 months before enrollment Hypertension

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Explorative
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blood donation and transfusion<br>Donation and reinfusion of 1 unit whole blood and 130 mL packed red blood cells, respectively. Blood samples were collected at 8 weeks prior to donation for 12 subjects and 2 weeks prior to donation by 12 subjects. Blood samples were collected 3, 7, 14, 21, and 28 days after donation and 3, 6, 24 hours and 2, 3 and 6 days after reinfusion of blood. | Procedure: Blood donation and blood transfusion<br>* 24 subjects (12 female, 12 male) is phlebotomized and four weeks later  130 mL packed red blood cells are re-infused in the same subjects.<br>|
| No Intervention: Control group<br>Blood samples collected with same frequency as described in the intervention arm. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin centration | The effect of the intervention on [Hb] levels will be investigated | 6 days after reinfusion | 
| reticulocyte percentage | The effect of the intervention on ret% levels will be investigated | 6 days after reinfusion | 
| OFF-score | The effect of the intervention on OFF-score (an algorithm computed from reticulocyte percentage and hemoglobin concentration resulting in a arbitrary value) will be investigated | 6 days after reinfusion | 
| Homeostatic markers of iron metabolism | Markers of iron metabolism such as hepcidin and erythroferrone are collected and analyzed for evaluation of iron metabolism during and after donation and reinfusion of blood. | 6 days after reinfusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endurance exercise performance measured as a preloaded 400 kcal time-trial | Endurance exercise performance are measured in a subgroup of 13 subjects. | 6 days after reinfusion. | 
| Maximal oxugen uptake (VO2max) | Maximal aerobic capacity is measured via a maximal oxygen uptake incremental test in a subgroup of 13 subjects. | 6 days after reinfusion. | 
| Mean corpuscular concentration | Markers of red blood cell size and hemoglobin content are collected and analyzed for Determining the impact of donation and reinfusion of blood. | 6 days after reinfusion. | 
| Mean corpuscular hemoglobin concentration | Markers of red blood cell size and hemoglobin content are collected and analyzed for Determining the impact of donation and reinfusion of blood. | 6 days after reinfusion. | 
| Mean corpuscular volume | Markers of red blood cell size and hemoglobin content are collected and analyzed for Determining the impact of donation and reinfusion of blood. | 6 days after reinfusion. | 
| Dried Blood Spots | Dried blood spots will be analyzed for the CD71/Band3 concentration as well as transcriptomic markers for reticolucytes including the ALAS2 L and LC. | 6 days after reinfusion. |