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17.3% at 3SD and 27.4% at NBG 2.2 in our study), 5.9% in never pregnant nor transfused women (vs. history of previous pregnancy (n=3992). The prevalence of HLA antibodies increased in women with greater numbers of pregnancy: 1.7%(zero), 11.2%(one), 22.5%(two), 27.5%(three) and 32.2%(four or more pregnancies), p<0.0001. Conclusion HLA class I and class II antibodies are detectable at low prevalence in male donors regardless of transfusion and in female donors without known immunizing events. The prevalence of HLA antibodies increases significantly with more pregnancies. These data will allow blood centers to estimate the impact of HLA antibody testing as a potential TRALI risk-reduction measure. Keywords: Betulinaldehyde HLA antibody, pregnancy, transfusion, transfusion related acute lung injury Introduction Human leukocyte antigen (HLA) antibodies mediate a number of important clinical effects including platelet transfusion refractoriness1 and hyperacute, acute, and chronic organ rejection.2 More recently HLA antibodies in donated blood have been implicated as the likely causative agent of most cases of transfusion related acute lung injury (TRALI).3,4 TRALI is a syndrome consisting of Betulinaldehyde non-cardiogenic pulmonary edema with hypoxia occurring during or within 6 hours of transfusion.5,6 TRALI is now the leading reported cause of transfusion-related mortality in the U.S.7 Among blood donors, HLA antibodies are found most frequently in multiparous women.8C10 In 2003 the United Kingdom (UK) began a TRALI risk-reduction effort by supplying transfusable fresh frozen plasma (FFP) that was predominantly from male donors; this measure resulted in a substantial decline in reported TRALI cases in the UK.11 A passive surveillance study of TRALI cases reported to the American Red Cross (ARC) from 2003C2005 indicated that 71% of the 38 reported probable TRALI-related fatalities and 75% (18/24) of the fatalities from transfused plasma were from leukocyte antibody positive female donors.12 The UK and ARC data prompted the AABB to publish an Association Bulletin (November 2006) outlining recommended measures to reduce the risk of TRALI and a timeline for implementation.13 In addition to using blood components only when indicated, the Bulletin recommended that blood collection facilities implement interventions to minimize the preparation of high-plasma volume components from donors known to be leukocyte alloimmunized or at increased risk of alloimmunization. High plasma volume components were defined as plasma components or apheresis platelets. The policy of supplying FFP or frozen plasma-24 hours (FP24) from predominantly male donors has now been widely implemented in the US. In comparison, defining and implementing the appropriate measures to mitigate the risk of TRALI from apheresis platelets remain problematic. Specifically, diverting all female platelet apheresis donors to whole blood donation would likely seriously affect the apheresis platelet supply and impact the commitment of long time donors. Another potential strategy is to selectively divert a subset of apheresis donors who are most likely to have HLA antibodies; donors could be screened for a history of pregnancy or transfusion, and donors with a positive history could be deferred or tested for HLA antibodies. HLA alloimmunization in blood donors is known to be associated with pregnancy8C10 Published studies have consistently demonstrated increasing HLA antibody prevalence with increasing parity although the number of donors in these studies is relatively small, and only Betulinaldehyde the study by Powers et al10 used current, more sensitive testing methods. Because of the small number of donors in these previous studies, it was not possible with confidence to compare HLA antibody prevalence for each parity level, to identify an independent effect of transfusion, or determine the effect of the time since the immunizing event. The Leukocyte Antibody Prevalence Study (LAPS) was designed to measure the prevalence of HLA class I and class II antibodies in a large number of donors with or without a history of Betulinaldehyde pregnancy or transfusion.14 Human neutrophil antigen antibody testing was also performed in a subset of donors and will be the subject of a subsequent publication. Methods LAPS was conducted between December 2006 and May 2007 as a prospective cross-sectional multi-center study by the National Heart, Lung, Mouse monoclonal to SORL1 and Blood Institute’s (NHLBI) Retrovirus Epidemiology Donor Study C II (REDS-II) program. All six REDS-II blood centers participated in the study; these included the American Red Cross New England Region (Dedham, MA), American Red Cross.