An association between decreased cardiopulmonary complications (TRALI and TACO) and implementation of universal leukoreduction of blood transfusions

Background—Cardiopulmonary adverse events after transfusion include acute lung injury (TRALI) and circulatory overload (TACO), which are potentially lethal and incompletely understood. Study Design and Methods—To determine whether the incidence of TRALI and TACO was affected by leukoreduction we conducted a retrospective, before and after study of acute transfusion reactions for the seven years prior to and after introduction of universal leukoreduction in 2000, involving 778,559 blood components. Results—Substantial decreases occurred in the rates of TRALI (−83%; from 2.8 cases per 100,000 components preto 0.48 post-universal leukoreduction; p=0.01), TACO (−49%; 7.4 to 3.8 cases per 100,000; p=0.03) and febrile reactions (−35%; 11.4 to 7.4 cases per 10,000; p<0.0001). The incidence of allergic reactions remained unchanged (7.0 per 100,000 preand post-universal leukoreduction). These outcomes were primarily attributable to decreased TRALI/ TACO associated with RBC and platelet transfusions (−64%) with notably smaller decreases associated with FFP or cryoprecipitate transfusions (−29%). The incidence of TRALI/TACO after 28,120 washed red cell and 69,325 platelet transfusions was zero. Conclusion—These data suggest novel hypotheses for further testing in animal models, in prospective clinical trials, and via the new US Hemovigilance System : (1) Is TACO or TRALI mitigated by leukoreduction? (2) Is the mechanism of TACO more complex than excessive blood volume? (3) Does washing mitigate TRALI and TACO due to platelet and RBC transfusions? Introduction Transfusion related acute lung injury (TRALI) 1 and transfusion associated circulatory overload (TACO) 2 are infrequent complications that are amongst the most commonly reported fatal events after blood transfusions. 3,4 The mechanism of TRALI has long been thought to be anti-white cell antibody (usually the donor’s) reacting with antigen positive cells, leading to a capillary leak syndrome. However, recent research suggests that other Correspondence to NB at: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 608, Rochester, NY 14642, Telephone 585/275-3189, [email protected]. Authorship Contributions NB had the initial idea for the study, analyzed the data and wrote the first and final drafts of the manuscript. KG and LBF collected data and edited the manuscript. All other authors contributed to the writing/editing of the manuscript. Disclosure of Conflicts of Interest NB and JMH have received lecture honoraria, consulting fees and research support from Pall Biomedical and Fenwal, manufacturers of leukoreduction filters, as well as from Caridian, manufacturers of cell washing equipment and supplies. The other authors declare they have no potential conflicts of interest. NIH Public Access Author Manuscript Transfusion. Author manuscript; available in PMC 2011 December 1. Published in final edited form as: Transfusion. 2010 December ; 50(12): 2738–2744. doi:10.1111/j.1537-2995.2010.02748.x. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript mechanisms, involving white blood cell (e.g., platelet activating factor) 5 and platelet derived (e.g., CD40L) mediators are important. 6 TACO has been presumed to be due to the inability of the recipient’s cardiovascular system to accommodate the volume infused. Universal leukoreduction has been associated, in one report, with a decreased incidence of adult respiratory distress syndrome in a cohort of critically ill patients. 7 The odds ratio for mortality in acute lung injury patients was 1.06 in recipients of leukoreduced red cells as compared with 1.14 in recipients of non-leukoreduced red cells in one recent cohort study. 8 In trauma patients in a randomized trial, no reduction in lung injury was associated with use of leukoreduced transfusions. 9 We initially hypothesized that leukoreduction might influence the overall incidence of TRALI, but not TACO. Pre-storage leukoreduction of blood components reduces the quantity of white cell and platelet derived mediators transfused. 10 We reasoned that universal leukoreduction, and subsequent removal of platelets (from transfused red cells), white blood cells (from both red cells and platelets) and their mediators, might decrease the risk of TRALI. We further hypothesized, based upon prior work of Silliman and colleagues, that saline washed red cells and platelets would be associated with a lower incidence of TRALI. 5 Recent findings support a role for white cell derived bioactive mediators such as IL-6 and TNF-α in heart failure,11 with which TACO shares some similarities. After initial review of the data, we further hypothesized that the incidence of TACO would also be influenced by leukoreduction of blood transfusions. We tested these hypotheses using retrospective analysis of transfusion reaction data.