the danish blood donor study - extending the gift of donation€¦ · 1. blood donation improves...

The Danish Blood Donor Study - extending the gift of donation: Give blood, save lives and create knowledge.

Christian Erikstrup

Chief physician, Associate Professor

Head of Blood Production and HIV/Hepatitis Testing

Dept. of Clinical Immunology

Aarhus University Hospital, Denmark

Why perform research in a blood bank?

• Natural extension of our work in the blood bank• Necessary for the study of health impact of

blood/plasma donation• Very cost efficient setup• Feasible for the study of generic research questions?

The Danish Blood Donor Study

Infrastructure for large population studiesAccess to participants: Mail, phone, homepage

Collection sites: Close to participants

Educated staff: Information, interviews, samples

Transport: Time, temperature

Laboratories: Sample handling, analysis

Storage Facilities: -80C freezers, preferably automated


Blood bank/donor organisation infrastructure✓ Access to participants: 250.000 blood donations

annually

✓ Collection sites: 200 sites nationally

✓ Educated staff: Nurses, tecnicians, physicians, public relations experts

✓ Transport: Look-back samples from each donation

✓ Laboratories: Extensive sample handling and analysis

✓ Storage Facilities: -20C automated freezer, -80C freezers


36 temporary inclusion sites

206 permanent inclusion sites

Examples of inclusion sites


Blood donorBlood

donationBlood for

transfusion Patient

Extending the gift of donation

Blood donorBlood

sample/questionnaire

Medical research

Future patients

Donor gift 1

Donor gift 2


The Danish Blood Donor Association (DBDA)• In DK, DBDA takes care of donor recruitment• The Danish Blood Donor Study:

tight collaboration between blood banks and DBDA• The Danish Blood Donor Study:

now part of the strategy for DBDA to use in the recruitment and retention of donors • Because research is important


OrganisationThe Danish Blood Donor Study

Databank

Steering GroupStudy responsibles

BLOOD BANK

Biobank Biobank:Whole blood (DNA)Plasma

Data Bank:ConsentQuestionnaire

Register data

BoardThe Danish Blood Donor Association Blood Bank Chiefs

Blood donation and healthBlood donor mortality reduced by 30% compared to the general populationHigh frequency donor mortality was lower than mortality for low frequency donors

SCANDAT225 million donationsfrom 1.6 million donorsto 2.2 million patients


Is blood donation healthy?2 possible explanations:1. Blood donation improves health2. Blood donors are more healthy – therefore they can/will

donate.The most healthy donors continue to donate – therefore they become high frequency donors

The effect of blood donation on health is still unknownA main aim of the study is to assess the effect of blood donation on healthPlasmapheresis: a new intervention to be studied


Inclusion of donor• Blood donors are informed about the study at

signup or while being bled• Nearly everybody (>95%) accepts• Routine tubes are marked for retrieval• Donor signs consent form• Donor fills questionnaire• Consent forms, questionnaires are sent to

blood centre• Marked archive samples, viral testing sample is

scanned and stored in biobank


Broad consentPermission to store samples in biobank(plasma and DNA)

Permission to collect info (questionnaire)

Permission to collect data from public registersNational Patient Register

ICD-10 codes from all contacts with hospitalsNational Prescription Register

ATX codes from all filled prescriptionsSocioeconomic data

Permission to contact donor again

Access to recipient data through SCANDAT and national registers


Questionnaire version 1

• Self reported health (Short Form 12)• Smoking status• Alcohol consumption• Physical activity• Diet• Iron intake• Height, weight, and waist• Contraception• Menopausal status.


StatusInitiated March 2010100,000 blood donors have been includedCurrent work dataset, merged and uploaded to StatisticsDenmark:81,898 participants256,097 person-years of follow-up by Dec 31 2014All baseline samples transferred to automated sample management system>500,000 plasma archive samples from every donation availablefor research

10 articles published – a lot in the pipeline


DiseaseDonationDonation DonationDonationDonation/inclusion

The Danish Blood Donor Association has helped with media relations


Blood donor study and research infrastructure

Research questions:Blood donor health questionsTransfusion medicine questionsGeneric health research questions

Infrastructure:Donor and recipient databaseNational health registersQuestionnaire databaseBiobank


Examples - Donor healthBlood donation and iron deficiency

Iron storage:Ferritin levels amongdonors predicted by donation frequency, sex and age. Limited effect of diet.

No effect of irondepletion on self reported health


Donations previous 3 years

Low ferritin is the strongest predictorof low hemoglobin


How can we assure that it is safe to donate?

Blood donation is heritable


Example – generic health questionObesity and risk of infection

Obesity is associated with cardiovascular diseases and type 2 diabetes

Obesity is associated with surgical-site infections.

No studies on obesity related risk of all-cause infection among otherwise healthy individuals

Aim - To examine the association between obesity and risk of infection

Methods: 37,808 donors; 106,609 person-years


Results1,233 participants had hospital contact due to for infection during106,609 person-years of observation; adjusted for age, sex, smoking

15,856 participants filled a prescription of antimicrobials during 58,834 person-years of observation

Women Men

Site of infection N HR (95% CI) P N HR (95% CI) P

Infections overall 575 1.44 (1.13-1.84) 0.003 658 1.53 (1.23-1.91) <0.0001

Abscesses 105 2.28 (1.40-3.70) 0.001 139 2.33 (1.54-3.54) <0.0001

Infections of the skin and subcutaneous tissue

87 0.85 (0.39-1.85) 0.69 201 2.24 (1.57-3.18) <0.0001

Respiratory tractinfections 144 1.60 (1.00-2.55) 0.05 143 1.27 (0.78-2.09) 0.34


Obesity – increased risk of infection

EpidemiologyJuly 2015

Obesity was associated with both hospitalization for infection and use of antimicrobials overall. Specifically:• Abscesses (both sexes)• Respiratory tract infections (women)• Dicloxacillin/flucloxacillin (both sexes)• Penicillin V (both sexes)

Risk of infection should be added to the long list of diseases associated with obesity


Plasmapheresis and risk of infection• Incidence of infection (prescriptions) after

plasmapheresis• Compared to incidence after whole blood donation


Are neuroinflammatory infectionsassociated with psychiatric events?• Retrieval from automated biobank:

7,600 cases (psychiatric disease, suicide attempts, trafic accidents)5,000 matched controls• Antibodies towards: Toxoplasma gondii, Herpes

simplex virus type 1, Cytomegalo virus, Epstein-Barr virus, Human herpes virus type 6, and Gliadin


Studies within the study• A nasal swab has been obtained from 2,050 donors;

aim 10,000• Primary aim: to study the associations of S. aureus colonisation with

morbidity (infections, metabolic disorders, autoimmune diseases)

• Secondary aims:Nasal microbiome and donor morbidityS. aureus/nasal microbiome and recipient outcome

• First finding: S. aureus colonisation more prevalent than previous studies: 50%


Other studies• Genetic testing and iron depletion• Predictors of hemoglobin• Attention-Deficit/Hyperactivity Disorder ADHD

spectrum in healthy Danes • Combined oral contraception and low-grade

inflammation• Blood screening for cytokine autoantibodies• HLA and infections• Environmental factors and HLA in Allergy/Asthma• Self perceived health

and infections amongIgA deficiency donors


Response from the blood donors• Extremely forthcoming• Some donors call me to hear how they can

participate in the study• Very often suggestions to new studies: e.g. migraine


Electronic questionnaire:Folding questions and the possibility for sub-grouptargeted questions


International collaboration• The Interval Study (UK) • The Insight Study (Holland)• The Finnish Red Cross Study• The Danish Blood Donor Study

• US REDS-III Studies• Héma-Québec • Australian Red Cross Blood Service


Exend the collaboration even further? Blood bank in Guinea-Bissau


Give blood, save lives, create knowledge


Dept. of Clinical Immunology, Aarhus University Hospital:

• Kathrine Agergaard Kaspersen

• Sebastian Kotzé

• Mikkel Steen Petersen

• Bjarne Møller

• Khoa Manh Dinh

• Christina Stilling

Dept. of Clinical Immunology, Naestved Hospital:

• Ole Birger Pedersen

Dept. of Clinical Immunology, Aalborg University Hospital:

• Kaspar René Nielsen

The Blood Donors in Denmark

• Jesper Villumsen

• Poul Erik Herner Petersen

Dept. of Clinical Immunology, Copenhagen University Hospital:

• Henrik Ullum

• Erik Sørensen

• Lise Wegner Thørner

• Kristoffer Sølvsten Burgdorf

• Andreas Striboldt Rigas

• Jakob Hjorth Von Stemann

Dept. of Epidemiology Research, Statens Serum Institut:

• Henrik Hjalgrim

• Klaus Rostgaard

Dept. of Clinical Immunology, Odense University Hospital:

• Mie Topholm Bruun

Dept. of Clinical Microbiology, Aarhus University Hospital:

• Lise Tornvig Erikstrup


the danish blood donor study - extending the gift of donation€¦ · 1. blood donation improves...

Documents