Preliminary Report
The British government has announced an incident in which a patient died after receiving blood six years earlier from a donor who later contracted variant Creutzfeldt-Jakob disease (vCJD). The case is the first report from anywhere in the world of the possible transmission of CJD via blood transfusion.
Case Report: In March 1996, a blood donor, who at the time was free of the signs of vCJD, donated blood to the National Blood Service. Shortly after, packed red cells from the donation were transfused into a patient over the age of 60 having surgery for a serious illness. The red cells were not subjected to a leuko-reduction procedure.
Although the donor showed no signs of vCJD at the time of donation, he subsequently developed vCJD and died in 1999. The recipient of the donation died in the autumn of 2003 and post-mortem examination of the recipient’s brain confirmed a diagnosis of variant CJD. The link between the donor and the recipient was first reported on December 9, 2003.
Further investigation revealed that the donor gave blood twice in 1996. The second recipient died six months following the transfusion due to a cause unrelated to variant CJD. Plasma from both donations was included in pools of plasma used in the manufacture of therapeutic blood components that included Factor VIII used by patients with hemophilia. It is unclear at this time, exactly who received plasma from the derivatives in the United Kingdom. Patients suspected of having received Factor VIII from these pools have been notified and are being monitored for signs of development of vCJD. No case of vCJD has been reported in any person with hemophilia.
Blood components from donors who subsequently developed vCJD have been transfused into 15 additional recipients, of which five received blood after leuko-depletion had been implemented. The earliest such transfusion was in 1993 and the latest in 2001. All are under health surveillance and to date, no signs of vCJD have developed.
Discussion: Although not proven, it is reasonable to assume that this incident represents a case of transmission of vCJD by blood transfusion for the following reasons: 1) Such transmission has been demonstrated in several animal species and is not unexpected. 2) The cellular components of blood contain the highest concentration of suspected infectious agent for vCJD and, therefore, are more likely to transmit the disease as compared with the other components or derivatives. 3) Leuko-depletion was not used on this donation. 4) The possible incubation period, six years, was appropriate for vCJD transmission via a peripheral route of infection (blood). 5) The age of the recipient was well outside the expected age range for acquired vCJD (15-40 years). 6) The probability of both donor and recipient acquiring the condition from eating contaminated beef would be quite small and is estimated to be 1:20,000 to 1:40,000.
Risk to patients receiving other blood products
The causative agent of vCJD, has been shown to be present in low concentration in the blood of experimental animal models of the disease. White blood cells (which are present in packed red cell transfusions) have a much greater concentration of infectivity than plasma). Plasma derivatives, such as clotting factor concentrates, are manufactured from plasma pools. The lower risk of infection from such concentrates is partly due to two factors: 1) the dilution of a contaminated donation by thousands of uncontaminated donations in the same plasma pool, and 2) the manufacturing process, which includes steps that are known from extensive laboratory studies to remove the infectious agent (e.g., precipitation, filtration, and column chromatography). Based upon animal experiments, the total reduction of infectious material in contaminated plasma has been calculated to be more than a million-fold (bulletin on this reduction - PDF format). As a result, health authorities have considered plasma derivatives to be among the lowest risk blood products for vCJD.
Geographic localization of risk
The risk of blood-borne transmission of vCJD is, for practical purposes, restricted to the U.K., where 145 people have died from the disease, and where by far the largest number of individuals have been potentially exposed to ‘mad cow disease’, the cause of the vCJD outbreak. Outside the U.K., only Europe and Japan have had cases of BSE, and the number of affected cattle is extremely small compared with the U.K.. Plasma collected from donors in the U.K. is not currently used for manufacturing plasma clotting factor concentrates. In addition, blood donor screening procedures used around the world have restrictions on donors who have resided in the U.K. and other countries where vCJD has been identified.
Exposure of hemophilia patients in the U.K. to vCJD
Plasma from a number of donors incubating vCJD was used in the U.K. to manufacture plasma-derived blood products prior to policy changes with regard to the use of U.K. plasma. As a result, several hundred hemophilia patients have used these products. These patients have been counseled and are under health surveillance for signs of developing vCJD. Reports indicate that currently, none have developed apparent vCJD.
Summary
- vCJD has occurred in a recipient of a donation of packed cells from a donor who subsequently developed vCJD.
- It is reasonable at this time to accept this as a possible blood transmission of vCJD. This occurrence would not be unexpected from the results of a number of animal experiments. (including transmission in sheep –the subject of previous WFH TSE Bulletins)
- The risk of such occurrences appears to be predominately a risk for recipients of blood components collected in the U.K.
- Donor screening procedures and blood banking policies initiated in countries throughout the world appear to be appropriate to reduce such transmissions to a minimum.
- Presently, clotting factor concentrates manufactured from plasma obtained outside the U.K. appear to carry a very low risk of transmission of vCJD because of the exclusion of potential donors incubating vCJD and the reduction of potential agents by the manufacturing processes. Continued vigilance is important to identify any changes in the level of suspected risk.
- WFH will continue to monitor this situation and we shall keep you informed.
This statement was prepared by the following members of the World Federation of Hemophilia TSE Task Force: Brian O'Mahony, Dr. Bruce Evatt, Dr. Paul Giangrande, and Dr. Paul Brown
December 19, 2003
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