The Pathogenetic Background of Transfusion-Associated Acute Lung Injury Cannot Be Confined to the Passive Transfer of Donor Leucocyte Antibodies to Transfusion Recipients

Abstract

When considering severe life-threatening transfusion complications, the transfusion-associated acute lung injury (TRALI) syndrome is currently the most outstanding challenge to transfusion medicine. Several haemovigilance systems in the UK, in France and in the USA identified TRALI to be the most frequent cause of transfusion-associated death, even if cases of ABO mistransfusion are included [1]. Data from the UK, accumulated 1996 through 2005 by the British Serious Hazards of Transfusion (SHOT) initiative, reported on 38 cases of transfusion-associated death at least possibly due to TRALI [2]. According to SHOT, for the observation period 1999 through 2005 the residual risk for components implicated in severe TRALI with an imputability level of ‘highly likely/probably’ was 1:76,000 for plasma-rich components (e.g. fresh frozen plasma (FFP) and platelet concentrates (PC)) and 1:440,000 for plasma-poor components (e.g. red cell concentrates (RCC) in additive solution) [3]. The French Health Products Safety Agency registered 10 transfusion-associated deaths at least ‘probably’ attributable to TRALI from 2002 to 2005 [4]. The American Red Cross TRALI surveillance study revealed 38 fatalities of probable TRALI between 2003 and 2005 [5]. For the USA, the risk of TRALI in transfusion recipient fatalities was calculated to be in the range of 1:2.5 Mio for RCC transfusion, 1:203,000 for FFP transfusion, 1:321,000 for apheresis PC transfusion and 1:2.1 Mio for whole blood-derived pooled PC transfusion. In Germany, an intensified surveillance study was performed by the Paul Ehrlich Institute (PEI) from January 2006 to July 2007. During this period 31 severe TRALI cases with 7 fatalities were observed. Of note, in the majority of transfusion recipients with severe TRALI, females with a history of at least one previous pregnancy (many of them with detectable antibodies to leucocyte antigens (LC-AB)) were identified as donors of the implicated blood components. This was a uniform finding in haemovigilance systems and TRALI studies as demonstrated by data from the SHOT initiative (2003–2005 41 TRALI cases highly likely or probable; 29/41 LC-AB-positive females (70%)), the ARC surveillance study (2003–2005 38 fatalities due to TRALI; 27/38 LC-AB-positive females (71%)) or the PEI surveillance study (2006–2007 31 TRALI cases highly likely; 21/31 LC-AB-positive females (68%)).