The distribution of infectivity in blood components and plasma derivatives in experimental models of transmissible spongiform encephalopathy

BACKGROUND: The administration of blood components from donors who subsequently develop Creutzfeldt‐Jakob disease has raised the issue of blood as a possible vehicle for iatrogenic disease. STUDY DESIGN AND METHODS: We examined infectivity in blood components and Cohn plasma fractions in normal huma...

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Bibliographic Details
Published in:	Transfusion (Philadelphia, Pa.) Vol. 38; no. 9; pp. 810 - 816
Main Authors:	Brown, P., Rohwer, R. G., Dunstan, B. C., MacAuley, C., Gajdusek, D. C., Drohan, W. N.
Format:	Journal Article
Language:	English
Published:	Edinburgh, UK Blackwell Science Ltd 01-09-1998 Blackwell Publishing
Subjects:	Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Biological and medical sciences Blood Component Removal Blood Component Transfusion - adverse effects Blood Donors Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis Creutzfeldt-Jakob Syndrome - transmission Cricetinae Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Humans Medical sciences Mice Neurology Plasma Prion Diseases - transmission Risk Assessment Scrapie - transmission Transfusions. Complications. Transfusion reactions. Cell and gene therapy Blood product Human Animal model Plasma Nervous system diseases Rodentia Transmission Blood Cerebral disorder Infection Vertebrata Blood cell Mammalia Mouse Animal Blood donation Central nervous system disease Risk factor Degenerative disease Prion Spongiform encephalopathy Creutzfeldt Jakob disease
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Summary:	BACKGROUND: The administration of blood components from donors who subsequently develop Creutzfeldt‐Jakob disease has raised the issue of blood as a possible vehicle for iatrogenic disease. STUDY DESIGN AND METHODS: We examined infectivity in blood components and Cohn plasma fractions in normal human blood that had been “spiked” with trypsinized cells from a scrapie‐infected hamster brain, and in blood of clinically ill mice that had been inoculated with a mouse‐adapted strain of human transmissible spongiform encephalopathy. Infectivity was assayed by intracerebral inoculation of the blood specimens into healthy animals. RESULTS: Most of the infectivity in spiked human blood was associated with cellular blood components; the smaller amount present in plasma, when fractionated, was found mainly in cryoprecipitate (the source of factor VIII) and fraction I+II+III (the source of fibrinogen and immunoglobulin); almost none was recovered in fraction IV (the source of vitamin‐K‐dependent proteins) and fraction V (the source of albumin). Mice infected with the human strain of spongiform encephalopathy had very low levels of endogenous infectivity in buffy coat, plasma, cryoprecipitate, and fraction I+II+III, and no detectable infectivity in fractions IV or V. CONCLUSION: Convergent results from exogenous spiking and endogenous infectivity experiments, in which decreasing levels of infectivity occurred in cellular blood components, plasma, and plasma fractions, suggest a potential but minimal risk of acquiring Creutzfeldt‐Jakob disease from the administration of human plasma protein concentrates.
Bibliography:	ArticleID:TRF5411 istex:E8B4A23F08629D41702A760DE5E397BB0C5A8E7F ark:/67375/WNG-7LSHLFT8-2 Claudia MacAuley, LAT, General Manager, TSE Validation Laboratory, Baltimore Research and Education Foundation, Veterans Affairs Medical Center, Medical Research Service. Robert G. Rohwer, PhD, Director, Molecular Neurovirology Laboratory, Veterans Affairs Medical Center, Medical Research Service; and Assistant Research Professor, Neurology, University of Maryland, Baltimore, MD. D. Carleton Gajdusek, MD, Laboratory Chief, Laboratory of CNS Studies (retired). Bryan C. Dunstan, BA, Baltimore Research and Education Foundation, Veterans Affairs Medical Center, Medical Research Service. William N. Drohan, MD, Senior Director, Plasma Development, Jerome H. Holland Laboratory, American Red Cross, Rockville, MD. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0041-1132 1537-2995
DOI:	10.1046/j.1537-2995.1998.38998408999.x