Authors' objectives:

Leukocytes, as part of transfusions, can cause a variety of side-effects such as febrile reactions, platelet refractoriness, and transmission of viruses like the cytomegalovirus. In addition, transfused leukocytes may suppress the recipient's immune response thereby increasing the risk of infection or malignancy. Therefore, reduction of leukocytes in blood and platelet transfusions may potentially reduce the frequency of these adverse events and save costs.

Currently, third generation adhesion filters exist which can achieve a three log reduction of the original leukocyte load. This study examines the efficacy of various filtration techniques and compares their costs and their potential savings. More specifically, it compares the efficacy of various filtration techniques in reducing the leukocyte load of transfused blood components (apheresis platelets, pooled platelets and red blood cells), their cost, as well as the savings associated with a reduction in treating the adverse vents related to transfused leukocytes.

Authors' results and conclusions: Clinical Efficacy Non Hemolytic Febrile Transfusion Reactions: Non Hemolytic Febrile Transfusion Reactions (NHFTR) are the most common leukocyte-related adverse effects of blood transfusions. Pre-or post-storage filtered transfusions prevent most febrile reactions to red blood cell transfusions and in this respect, the advantage of pre-storage filtration has not been proven in a randomized controlled trial. However, platelet transfusions are associated with a higher rate of adverse events, and post-storage filtration of platelets is not as effective as post-storage filtration of red blood cells. In the case of platelets, pre-storage filtration offers the advantage of preventing the production of some leukocyte mediated cytokines during the storage period. Infections: the risk of transmission of leukocyte born viruses such as the cytomegalovirus (CMV) via transfusion of red blood cells and platelets is markedly decreased by leukofiltration. Consequently, leukofiltration is increasingly accepted as an alternative to CMV screening of blood components. However, for other viral or bacterial/protozoal infections, we found no evidence that leukofiltration is an alternative to existing screening programs. Thus, apart from CMV, the impact of leukofiltration on the prevention of transfusion-related infections remains unknown. Platelet-refractoriness: To prevent thrombocytopenic bleeding due to high dose chemotherapy, prophylactic platelet transfusions are usually given. The ability of these transfusions to increase the platelet count can be inhibited if the recipient has an immune response due to prior HLA- alloimmunization to donor blood components, mainly leukocytes. Leukofiltration reduces the incidence of alloimmunization and therefore platelet refractoriness particularly in desensitized patients. However, despite several experimental and retrospective studies, no randomized controlled trial exists that has demonstrated an advantage of pre- over post-storage filtration. Immunomodulation: an immunomodulatory effect of blood transfusions in humans is still controversial. A recent meta-analysis of unconfounded randomized controlled trials concluded that any possible effect would be smaller than 25% (relative risk reduction of postoperative infection, cancer recurrence after surgery). At present, there is no evidence from clinical trials that the timing of filtration influences immunomodulation. Cost Comparison The cost of each of the nine filtration techniques was assessed in both single and multi- transfused patients. This cost included the cost of filters, the cost of related activities such as inventory management and overhead costs and the cost of treating adverse reactions. The cost of treating adverse events is itself dependent on the number of transfusions, the efficacy of the leukoreduction technique and the cost of treating the particular adverse reaction. We then calculated the cost impact for three main strategies, the first being filtering all blood components in a blood centre, the second, filtering all components in a hospital blood bank, and the third, filtering all blood components at the patient bedside. This analysis focused on the costs associated with filtration and does not take into account the cost of producing different blood components. Thus the cost of one apheresis platelet cannot be compared directly with the cost of one pooled platelet. In addition, health-related-quality-of-life under different techniques were not examined. Costs are presented in 1997 Canadian dollars and have been estimated from the perspective of the health care system. For the purpose of the cost comparison, the benefit of the doubt was given to pre-storage filtration. A higher efficacy for pre-storage was used than for post-storage filtration in reducing adverse events although this has not been proven in randomized controlled trials. It was assumed that leukofiltration can prevent alloimmunization and thus platelet refractoriness in a certain percentage of patients at risk. Febrile reactions were assumed to occur more frequently in multi-transfused patients than single-episode transfused patients. This analysis revealed that the implementation of a 100% filtration strategy in a blood centre would cost $46.37 million and takes into account the savings resulting from a decrease in adverse events. Filtration at a hospital blood bank would cost $25.95 million, and at a hospital bedside, this cost would total $20.19 million. The much higher cost of pre-storage leukofiltration is mainly due to two factors that are specific to pre-storage filtration. Firstly, with pooled platelets, five filters have to be used instead of a single one for the production of one platelet concentrate. Also, since more blood components are produced than actually transfused to patients, 30% more pooled platelet concentrates have to be filtered in a blood centre level compared to hospital filtration. An examination of the cost of each filtration technique reveals that the impact of red blood cell filtration drives the overall cost of strategies. When looking at apheresis platelets in isolation, leukofiltration is cost saving regardless of the timing of leukofiltration. For pooled platelets, the case is different. Post-storage blood bank or bedside techniques are cost saving compared to pre-storage filtration. The fact that savings can be achieved with platelet transfusions is not surprising since around 70% of all platelet components are directed at multi-transfused patients. This is the patient group who benefit most from leukofiltration. On the other hand, 90% of all red blood cells are directed at single-transfused patients such as surgical or obstetric patients. This patient group does not benefit as much from leukofiltration, and as a result the savings achieved by filtration do not outweigh its costs. Since the impact of an immunomodulatory effect of transfused leukocytes is now not known the results could change if this effect is better understood. An extensive sensitivity analysis was performed and it showed that these results were robust.

Authors' recommendations: It can be concluded that a 100% filtration strategy is not cost-saving, whatever the timing of leukofiltration. However, for certain patient groups, notably those who require either frequent red blood cell or platelet transfusions, leukofiltration can be cost saving.

Authors' methods: Systematic review

Project Status: Completed

URL for project: https://www.ccohta.ca/pubs/english/leukoreduct/index.html

Year Published: 1998

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Canada

Organisation Name: Canadian Coordinating Office for Health Technology Assessment

Contact Address: 600-865 Carling Avenue, Ottawa, ON K1S 5S8 Canada. Tel: +1 613 226 2553, Fax: +1 613 226 5392;

Contact Name: requests@cadth.ca

Contact Email: requests@cadth.ca

Copyright: Canadian Coordinating Office for Health Technology Assessment, 1998