The case against universal white blood cell reduction

Both basic and clinical studies have documented the efficacy of white blood cell (WBC) reduction in reducing the risk of three complications of allogeneic blood transfusion (ABT). These are: (1) febrile, non-haemolytic transfusion reactions (FNHTRs); (2) refractoriness to random-donor platelet transfusion that is due to HLA alloimmunization; and (3) transmission of Cytomegalovirus (CMV) [1]. These benefits from WBC reduction can be secured through selective WBC reduction of the cellular blood components destined for transfusion to specific categories of patients, i.e. (1) patients with a history of FNHTRs; (2) patients at risk of platelet refractoriness because of the receipt of multiple platelet transfusions; or (3) patients at risk of CMV disease [1]. Savings realized by the benefits accrued by these three categories of patients are sufficient to offset the cost of selective WBC reduction for such patients [2,3], but they cannot offset the cost of universal WBC reduction of all transfused cellular blood components. WBCs in units of non-WBC-reduced blood components do not contribute to product efficacy, and may be regarded as contaminants that potentially reduce transfusion safety. Prestorage WBC reduction of cellular blood components removes donor WBCs before they undergo apoptosis or necrosis, and before they release breakdown products at 4 ° C or cytokines at room temperature. Furthermore, although adverse transfusion reactions have been associated with the use of WBC reduction filters [4–6], it has been concluded that aside from specific device (filter) failures, there are no clinically significant adverse effects associated with leucocyte reduction. In fact, the reported severe hypotensive reactions to WBCreduced blood components have been associated only with the transfusion of blood components filtered at the bedside [7]. Blood components that are WBC-reduced by prestorage filtration do not cause hypotensive reactions, and – based on current knowledge – the transfusion of these blood components is free from complications associated with the use of WBC reduction filters. For these reasons, in the absence of considerations of cost, many transfusion medicine professionals readily endorse the implementation of universal WBC reduction by prestorage filtration. It is often assumed that such a policy can extend to all patients the three proven benefits of WBC reduction [8]. Although patients who have not suffered FNHTRs, are not receiving long-term platelet transfusions, and are not at risk of developing CMV disease may derive no immediate benefit from prestorage WBC reduction, it is theorized that these patients may accrue a tangible benefit in the future. In 1999, the United Kingdom, Ireland, and Portugal implemented universal WBC reduction of all transfused cellular blood components, based on the hypothesis that this practice would prevent the then theoretical risk of transmission by transfusion of the agent of variant Creutzfeldt-Jakob disease (vCJD) [9,10]. France and Canada also implemented universal WBC reduction in 1999, primarily to enhance overall transfusion safety [10]. Following these developments, public debate began in the US and elsewhere regarding the appropriateness of introducing universal WBC reduction. In the US, the debate focused mainly, but not exclusively, on an examination of the efficacy of WBC reduction in preventing adverse immunomodulatory effects of ABT. This was because the prevention of the deleterious clinical effects of ABT-related immunomodulation (TRIM) [11–14] would apply to all patients and would thus justify universal WBC reduction. This review examines whether: (1) it is reasonable to implement universal WBC reduction in order to extend the three proven benefits of WBC reduction to all transfused patients; (2) sufficient evidence has accumulated from randomized controlled trials (RCTs) of the adverse TRIM effects to justify introduction of universal WBC reduction for the abrogation of these purported ABT effects; and (3) it is reasonable to invoke the precautionary principle in order to justify the introduction of universal WBC reduction for the prevention of adverse TRIM effects.