CREUTZFELDT JAKOB DISEASE (CJD) AND
Arell Shapiro, M.D.
Creutzfeldt Jakob Disease (CJD) is a rare, rapidly fatal dementing
illness characterized by spongiform degeneration of the Central Nervous System (spongiform
encephalopathy). Cases are generally either sporadic or familial. However, CJD
transmission has been associated with receipt of human-derived pituitary growth hormone,
transplantation of infected dura mater and corneal grafts, contaminated EEG electrodes and
Despite the fact that no case of transmission through blood transfusion
or blood derivative has been documented, nor has it been linked to hemophilia, concern
about transmission of this disease has led to the permanent deferral of blood donors who
have family members diagnosed with CJD.1
Numerous Blood Product Advisory Committee meetings have discussed the
issue of the possibility of transmission of CJD by blood components and plasma
derivatives. Overall their conclusions are that the risk is theoretical, but appropriate
precautions are indicated. Aside from the deferral of donors with risk, quarantine of
in-date products and lookback is performed on units which are donated by individuals who
are later recognized to have a risk for CJD such as family members with CJD, having
received a dura mater transplant graft or human derived pituitary growth hormone.3
Finally, quarantine of plasma and plasma derivatives when donors are later found to have
risk, has led to severe shortages of vital factor concentrates and immune globulin
The etiologic agent of spongiform encephalopathies is believed to be a
prion. The name prion is coined from proteinaceous infectious particle. It is believed to
be devoid of nucleic acid, encoded by a single copy host gene (PRNP) present at the short
arm of chromosome 20. The function of normal cellular isoform (PrPC) is
unknown; there are both membrane and secreted forms. Neurons contain high concentrations
of PrPC .
The modified form PrPSc is pathologic due to resistance to
proteolytic digestion, and spontaneous aggregation to produce rod-like or fibrillary
particles. This protein can be isolated from brains of animals and humans with spongiform
degenerative diseases. Tests to detect infection with CJD are currently research level
assays of unknown sensitivity and specificity.
Concerns About New Variant CJD
New Variant CJD was first reported in the United Kingdom April,1996,
upon recognition of 10 of 207 cases of CJD which were distinguishably different.6
The patients median age was 29 and the clinical manifestations were early behavioral
changes, absence of typical EEG pattern seen with classic CJD. A UK advisory committee
concluded that the agent responsible for mad cow disease, bovine spongiform encephalopathy
(BSE) may be responsible for the new variant CJD, even though no epidemiologic link to BSE
has been identified.
Epidemiologic and Lookback Studies
A study performed in England and Wales between 1980-84 and 1990-92
found that the frequency of blood transfusions or donations did not differ between CJD
cases and matched controls.5 Lookback studies of blood recipients who received
blood from donors subsequently diagnosed with CJD, show no development of CJD nor CNS
What is next?
An article by Klein, et al examining, the role of the white blood cell
in CJD transmission has received much attention.7 In a mouse model, they
identified B cells as a limiting factor in the development of scrapie after peripheral
inoculation. The suspicion that B cells may play a role in spongiform encephalopathies has
lead to a international trend toward leukoreduction of all blood and blood components. At
the Sept.98 Blood Products Advisory Committee meeting of the FDA the idea of
"universal" leukoreduction was embraced, but for reasons other than the
prevention of CJD transmission.
CJD and possibility of its transmission through blood continues to be a
topic of great interest in this country and internationally. The risk continues to be only
theoretical despite multiple lookback and surveillance studies. More definitive answers
will be long in coming given the very low incidence of CJD, its long incubation period and
lack of diagnostic tests to detect its presence or latent phase in humans.
- Guidance on Notifying Recipients of Blood Components from a Donor Who Subsequently Was
Diagnosed as Having Creutzfeld-Jakob Disease (CJD) and/or CJD Risk Factors, AABB
Association Bulletin #96-4, May 3, 1996.
- Surveillance for Creutzfeldt-Jakob DiseaseUnited States, Morbidity and Mortality
Weekly Report, Vol. 45 No. 31, August 9, 1996
- "Revised Precautionary Measures to Reduce the Possible Risk of Transmission of
Creutzfeldt-Jakob Disease (CJD) by Blood and Blood Products" FDA Memorandum, December
- "Guidance on Notifying Recipients of Blood Components from a Donor Who Subsequently
Was Diagnosed as Having Creutzfeldt-Jakob Disease (CJD) and/or CJD Risk Factors",
AABB Association Bulletin #96-4.
- Esmonde, T.F. et al, "Creutzfeldt-Jakob disease and Blood Transfusion" Lancet
- Will, R.G. et al "A new variant of Creutzfeldt-Jakob disease in the UK" Lancet
- Klein, M.A., et al A Crucial Role for B Cells in Neuroinvasive Scrapie, Nature 390:18,
December 25, 1997.
- Sullivan, M.T. et Creutzfeldt-Jakob Disease Investigational Lookback Study, Abstract
AABB Annual Meeting 1996.
For questions regarding the CJD and
Transfusion Risk, please contact the Blood Center Physicians at
CBB (412) 209-7320 or
LifeSource at (847) 803-7825.
Copyright © 1998, Institute For Transfusion
Copies of the Transfusion Medicine Update can be obtained by calling
Deborah Small at (412)209-7320; or by e-mail: email@example.com
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