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November / December, 1998


CREUTZFELDT JAKOB DISEASE (CJD) AND BLOOD

Arell Shapiro, M.D.


INTRODUCTION

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 surgical instruments.

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 products.

BACKGROUND

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 disease.8

 

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.

 

SUMMARY

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.

 

References

  1. 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.
  2. Surveillance for Creutzfeldt-Jakob Disease—United States, Morbidity and Mortality Weekly Report, Vol. 45 No. 31, August 9, 1996
  3. "Revised Precautionary Measures to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease (CJD) by Blood and Blood Products" FDA Memorandum, December 11, 1996.
  4. "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.
  5. Esmonde, T.F. et al, "Creutzfeldt-Jakob disease and Blood Transfusion" Lancet 1993; 341:205-7.
  6. Will, R.G. et al "A new variant of Creutzfeldt-Jakob disease in the UK" Lancet 1996; 347:921-925.
  7. Klein, M.A., et al A Crucial Role for B Cells in Neuroinvasive Scrapie, Nature 390:18, December 25, 1997.
  8. 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 Medicine


Copies of the Transfusion Medicine Update can be obtained by calling Deborah Small at (412)209-7320; or by e-mail: dsmall@itxm.org

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