NR AKRC
AU Seghatchian,J.
TI nvCJD and leucodepletion: an overview.
QU Transfusion Science 2000 Feb-Apr; 22(1-2): 47-8
PT journal article
VT
A variant of "Creuzfeldt Jacob Disease'', was identified in 1996 and related to harbouring a new variant of prion protein (PrP), possibly transported via lymphocytes harbouring the PrP to the nervous system causing nvCJD. Up to now 40 cases have been reported. While the risk or the transmission of nvCJD through blood transfusion still remains to be proven, in the UK however, a planned strategy for universal leucodepletion has been adopted as a risk reduction measure. This is in response to a recent announcement by the Secretary of State for Health in July 1997 that we should take all feasible precautions to reduce the theoretical risk of transmission of nvCJD by blood transfusion.
In February 1998 the National Blood Service in consensus with the UK Standing Advisory Committee on Blood components (SAGBC) agreed not to alter the current definition of leucocyte depletion as stated in the current UK guidelines (i.e. <5 x 10^6). This was in recognition that most of the current leucoreduction processes may not be able to achieve a lower standard with 100% consistency and that the "critical dose'' of leucocytes with regard to nvCJD transmission was unknown and that leucocyte depletion is only a risk reduction strategy.
Accordingly for an effective implementation program in the UK, a target date of 1 November 1999 was set for all blood components to be leucodepleted at source, within 24 h of collection. It was felt essential that the filtration process be carried out in a controlled environment that allows adequate process monitoring to ensure the filtration process is under control and that the derived products contain less than 5 x 10^6 per adult therapeutic dose with more than 99% consistency and 95% confidence limit. Thus a national approach to statistical process monitoring, "SPM'', was launched for analysis of leucocyte content in leucodepleted blood components to ensure reproducibility and consistency of the process.
While the virtue of a universal leucodepletion approach has not been universally accepted as discussed in this international forum, there is still no clear evidence as to the minium levels of residual leucocytes or lymphocyte subsets needed to prevent certain immunomodulatory effects and transmission of infection including CMV and HTLV. It was felt that this was a good opportunity to undertake further clinical trails to relate the clinical impact of universal leucodepletion to both filtration-induced untoward effects and bacterial retention/growth, as it is possible that the filtration process may remove cell-associated viruses and bacteria either directly or indirectly. Contact activation and changes in hemostatic parameters and functional integrity/ aggregation states of cellular components may also occur. In this respect a comparative analysis of leucodepleted products produced with or without WBC filtration, in terms of new quality parameters such as changes in cellular integrity, subpopulation and microvesiculation would be of interest.
The true distribution of abnormal prion in various blood components is still unknown. The possible roles played by cell-derived fragments and microvesicles in leucofiltered products also need in depth analysis as some filters may retain and others may generate cellular fragments and microvesicles due to shear induced injury. In addition there is also some evidence that in certain donation/filter combination, possibly due to high levels of microvesicles or large cells/cellular aggregate or "pinched'' and/or structurally/functionally abnormal WBC, frequently lead to membrane blockage or filtration failure. This is of particular relevance to sickle cell trait. A comprehensive evaluation of donor related issues and filtration failure and recurrent blockage is also urgently needed so that a national evidence-based policy can be established throughout the NBS.
Finally, while the concept of multi-component system is pursued with enthusiasm, it is important to define the practical sensitivity of leucocyte counting techniques for leucodepleted blood components at the levels relevant to the "decision making point'' as currently applied by the UK guidelines and the Council of Europe. In this respect the use of IMAGN 2000 may be a good option as the reagents and procedure are standardised making results comparable among various sites. This, nevertheless, needs to be supported by a high frequency proficiency testing scheme.
This International Forum focuses on the current position on selective/universal leucodepletion; and the extent of knowledge gathered so far on the potential utility of various laboratory and clinical strategies of universal leucodepletion programme under four interrelated topics:
1. Leucodepletion and transfusion transmitted infection
2. International perspectives on universal/selective leucodepletion
3. Validation of some leucodepletion processes
4. Quality Monitoring and statistical process monitoring
I am grateful to our speakers who are sharing their expertise with us on topics of their interest and to supportive manufacturers as without their help this meeting would not be realised. I also with to express my sincere thanks to Dr Pranee Krailadsiri, Margaret charleston and Kim Smith for their unreserved help in the organisation of the meeting and the timely preparation of the proceeding.
MH Annexin V/blood; Blood Component Removal/*methods/standards; Blood Platelets; Creutzfeldt-Jakob Syndrome/*blood; Erythrocytes; Great Britain; Human; *Leukocytes; Prions/blood; Quality Control
AD National Blood Service, North London, Colindale Avenue, London, UK, Tel.: +44-181-258-2839; fax: +44-181-258-2970; E-mail address: jerhard.seghatchian@nbs.nhs.uk (J. Seghatchian)
SP englisch
PO England