Gustaf Edgren, MD, PhD; Henrik Hjalgrim, MD, PhD, DrMedSci; Klaus Rostgaard, MSc; Paul Lambert, PhD; Agneta Wikman, MD, PhD; Rut Norda, MD, PhD; Kjell-Einar Titlestad, MD, PhD; Christian Erikstrup, MD, PhD; Henrik Ullum, MD, PhD; Mads Melbye, MD, DrMedSci; Michael P. Busch, MD, PhD; Olof Nyrén, MD, PhD
Acknowledgment: The authors are greatly indebted to all of the blood banks in Sweden and Denmark that collected and contributed data to this study.
Grant Support: The assembly of the SCANDAT2 database and the conduct of this study were made possible through grants from the Swedish Research Council (2011-30405 and 2007-7469), the Swedish Heart-Lung Foundation (20090710), the Swedish Society for Medical Research (Dr. Edgren), and the Danish Council for Independent Research (2009B026).
Disclosures: Dr. Hjalgrim reports a grant from the Danish Council for Independent Research during the conduct of the study. Dr. Nyrén reports grants from the Swedish Research Council and the Swedish Heart-Lung Foundation during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-2421.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Edgren (e-mail, firstname.lastname@example.org).
Requests for Single Reprints: Gustaf Edgren, MD, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden; e-mail, email@example.com.
Current Author Addresses: Drs. Edgren and Nyrén: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden.
Drs. Hjalgrim and Melbye and Mr. Rostgaard: Department of Epidemiology Research, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen S, Denmark.
Dr. Lambert: Department of Health Sciences, University of Leicester, Adrian Building, University Road, Leicester LE1 7RH, United Kingdom.
Dr. Wikman: Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, C2:66 Huddinge, SE-177 77 Stockholm, Sweden.
Dr. Norda: Department of Immunology, Genetics and Pathology, Uppsala University, Akademiska Sjukhuset, SE-751 85 Uppsala, Sweden.
Dr. Titlestad: Department of Clinical Immunology, Odense University Hospital, Søndre Boulevard 29, DK-5000 Odense, Denmark.
Dr. Erikstrup: Department of Clinical Immunology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8000 Aarhus, Denmark.
Dr. Ullum: Department of Clinical Immunology, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Dr. Busch: Blood Systems Research Institute, 270 Masonic Avenue, San Francisco, CA 94118.
Author Contributions: Conception and design: G. Edgren, H. Hjalgrim, R. Norda, M.P. Busch, O. Nyrén.
Analysis and interpretation of the data: G. Edgren, H. Hjalgrim, K. Rostgaard, P. Lambert, A. Wikman, R. Norda, M. Melbye, M.P. Busch, O. Nyrén.
Drafting of the article: G. Edgren, R. Norda, M.P. Busch.
Critical revision of the article for important intellectual content: G. Edgren, H. Hjalgrim, K. Rostgaard, A. Wikman, K.E. Titlestad, C. Erikstrup, H. Ullum, M. Melbye, M.P. Busch, O. Nyrén.
Final approval of the article: G. Edgren, H. Hjalgrim, K. Rostgaard, P. Lambert, A. Wikman, R. Norda, K.E. Titlestad, C. Erikstrup, H. Ullum, M. Melbye, M.P. Busch, O. Nyrén.
Provision of study materials or patients: G. Edgren, R. Norda, C. Erikstrup, H. Ullum.
Statistical expertise: G. Edgren, H. Hjalgrim, K. Rostgaard, P. Lambert.
Obtaining of funding: G. Edgren, H. Hjalgrim.
Administrative, technical, or logistic support: G. Edgren, H. Hjalgrim, A. Wikman, C. Erikstrup.
Collection and assembly of data: G. Edgren, H. Hjalgrim, K. Rostgaard, R. Norda, K.E. Titlestad, C. Erikstrup, H. Ullum.
Edgren G, Hjalgrim H, Rostgaard K, Lambert P, Wikman A, Norda R, et al. Transmission of Neurodegenerative Disorders Through Blood Transfusion: A Cohort Study. Ann Intern Med. 2016;165:316-324. doi: 10.7326/M15-2421
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Published: Ann Intern Med. 2016;165(5):316-324.
Published at www.annals.org on 28 June 2016
The aggregation of misfolded proteins in the brain occurs in several neurodegenerative disorders. Aberrant protein aggregation is inducible in rodents and primates by intracerebral inoculation. Possible transfusion transmission of neurodegenerative diseases has important public health implications.
To investigate possible transfusion transmission of neurodegenerative disorders.
Retrospective cohort study.
Nationwide registers of transfusions in Sweden and Denmark.
1 465 845 patients who received transfusions between 1968 and 2012.
Multivariable Cox regression models were used to estimate hazard ratios for dementia of any type, Alzheimer disease, and Parkinson disease in patients receiving blood transfusions from donors who were later diagnosed with any of these diseases versus patients who received blood from healthy donors. Whether excess occurrence of neurodegenerative disease occurred among recipients of blood from a subset of donors was also investigated. As a positive control, transmission of chronic hepatitis before and after implementation of hepatitis C virus screening was assessed.
Among included patients, 2.9% received a transfusion from a donor diagnosed with one of the studied neurodegenerative diseases. No evidence of transmission of any of these diseases was found, regardless of approach. The hazard ratio for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy donors was 1.04 (95% CI, 0.99 to 1.09). Corresponding estimates for Alzheimer disease and Parkinson disease were 0.99 (CI, 0.85 to 1.15) and 0.94 (CI, 0.78 to 1.14), respectively. Hepatitis transmission was detected before but not after implementation of hepatitis C virus screening.
Observational study design, underascertainment of the outcome, and possible insufficient statistical power.
The data provide no evidence for the transmission of neurodegenerative diseases and suggest that if transmission does occur, it is rare.
Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Society for Medical Research, and Danish Council for Independent Research.
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