title: Universal leucodepletion: an overview of some unresolved issues and the highlights of lessons learned.
abstract: Universal leucodepletion (ULD) has been introduced in several countries based on the evidence that selective leucodepletion improves the clinical safety of blood components and based on animal studies that TSE infectivity is 5-7 times higher in the buffy coat than in plasma. Therefore it is perceivable that the removal of the buffy coat, by filtration, removing both leucocytes and platelets, may prove beneficial in reducing the potential risk of transmission of variant CJD by blood components. The implementation of a ULD policy has created some new requirements: Validation/standardisation of various leucodepletion processes to ensure compliance with set specifications. Standardisation/harmonisation of sampling and low leucocyte counting technologies to ensure the interchangeability of results nationally. The establishment of external quality assessment schemes on 'real' leucodepleted products where the cells come in contact with the filter matrix, to monitor the low leucocyte counting performance, nationally. Assessment of filtration-induced generation/retention of major biological response modifiers (BRM), having potential for the development of transfusion reactions. Using these approaches we have identified that, while the overall leucodepletion performance has improved following harmonisation/standardisation of the operational and counting technologies, there are still some unresolved problems and ULD alone may not provide complete protection from some viral transmission such as HTLV and CMV infections or reduction of bacterial sepsis and generation of some BRM. Moreover, ULD has not fully abrogated febrile non-haemolytic transfusion reactions (FNHTR). Therefore the key issue is not the 3-4 log(10) reduction of residual leucocytes but the design of new generation filters or leucodepletion processes with better performance characteristics, to further reduce some specific leucocyte subsets and their fragments as well as reduce the activation of coagulation/complement/kinin and inflammatory systems. Efforts should also be made to reduce the rapid development of apoptotic/necrotic cells and the residual risk associated with plasma, which often contains a vast array of BRM, responsible for residual transfusion reactions. These could only be effectively achieved by working in cooperation with the suppliers of blood component technologies. This overview briefly highlights some of the unresolved issues related to ULD, based on the experience in the UK. Technical details can be found in the reading list provided at the end.
authors.affiliation: Blood Component Technology and Thrombosis/Haemostasis consultancy, 50 Primrose Hill Road, London NWS 3AA, UK. jseghatchian@btopenworld.com
authors.forename: Jerard
authors.initials: J
authors.lastname: Seghatchian
mesh_terms: D016207:Cytokines / Q000097:blood; D004868:Equipment Failure; D017707:Erythrocyte Transfusion / Q000009:adverse effects / Q000379:methods* / Q000706:statistics & numerical data; D005334:Fever / Q000209:etiology / Q000517:prevention & control; D005374:Filtration / Q000379:methods; D006680:HLA Antigens / Q000097:blood; D006801:Humans; D007937:Leukapheresis / Q000379:methods / Q000592:standards*; D007958:Leukocyte Count
chemical_list: D016207:Cytokines; D006680:HLA Antigens