April The American Red Cross experience with TRALI Richard J Benjamin MD PhD Chief Medical Officer American Red Cross, Biomedical Headquarters Washington DC

April Suspected TRALI Fatalities ( ): 72 reported Fatalities ( ) Eder et al Transfusion 47(4): ;2007

April Independent Review of TRALI Fatalities: Association with leukocyte antibodies P <0.001  2 - test Recipient Fatalities Eder et al Transfusion 47(4): ;2007

April Probable TRALI by Implicated Component: Eder et al Transfusion 47(4): ;2007

April Rate of Probable TRALI Fatality per 10 6 Distributed Units Fatality is correlated with female plasma exposure Proportion 48%35%48%48%48% female donors O.R.12.5* O.R. 7.9* * P<0.001

April Strategies to Reduce TRALI  Appropriate use of Blood products  Selective use of Male products  Donor history of transfusion or pregnancy  Testing for HLA and HNA antibodies  Others Pool & store platelets Platelet additive solutions Solvent detergent plasma

April Plasma Production in the ARC System (2005)

April Red Cross Pilot Program  ARC instituted a pilot program in 3 of 10 divisions to produce predominantly male plasma frozen within 24 hours (FP24) on October 1 st  Program assessed the manufacturing issues, not the clinical efficacy.  Products were temporarily labeled with gender at collection and triaged on receipt at manufacturing.  Process instituted as a business practice final product was not labeled customers were not notified used female AB plasma as needed.

April Tucson Birmingham Oakland Los Angeles Little Rock PortlandBoise St Louis Omaha Madison St Paul Nashville Louisville Atlanta Charlotte Columbia Roanoke Johnstown Columbus Ft Wayne Lansing Toledo Detroit Farmington Baltimore Cleveland Philadelphia Dedham West Henrietta San Juan Tulsa Wichita Mobile Peoria Wilkes-Barre Norfolk Male Predominant 24-hour Plasma Pilot: December % male 95.2% male 98.0% male 97.6% male Overall 72.7% FP24 Male

April  FFP (<8 hrs), FP24 (<24 hrs), and Cryo Poor Plasma  Selective use of male products achieving >95% male plasma distributions by November 2007 Longer term goal is 100% male plasma Leeway reserved to ensure availability  Currently collect enough AB plasma to ensure 92% Male  Will need to move to >80% FP24 (<24 hrs)  FFP (<8 hours) will become a specialty product  Final Product will not be labeled with Donor Gender  Apheresis Plasma (Auto-C, excluding concurrent)  Donor history + Testing (details still under evaluation) by November 2007  Apheresis Platelets and Concurrent Plasma  Donor history + Testing (details still under evaluation) by November 2008 Overview of Red Cross Approach 95% 5% Share of transfusable plasma distributions

April Overview: Impact on Customers FY02FY07 (YTD) FY08 FFPFP24 To achieve 95% male distributions and maintain fill rates, the American Red Cross will need to substantially increase the proportion of FP24 distributed (from 45% today). Specific messaging to Hospitals is being developed to notify and educate customers.

April % 67% 90% 53% 67% 63% Approach to Apheresis Products (in development) Proportion of Male Apheresis Donors

April Approach to Apheresis Products (in development)  Prestorage pooled whole blood-derived platelets are being developed as an alternative  We assume that we must test, though donor history may play a role  REDS II LAPS alloantibody data needed to define who should be screened What is the prevalence in untransfused males?  If a significant proportion of untransfused males harbor antibodies, will this necessitate universal testing? What is the incremental prevalence with transfusion? What is the incremental prevalence with pregnancy?

April Issues Regarding Testing for Alloantibodies  No FDA licensed assays for donor screening  No suitable technology for routine Human Neutrophil Antibody (HNA) screening  U.S. manufacturers are developing automated HLA class I and class II antibody screening technologies  Uncertainties remain What is the appropriate screening strategy? How do we define a clinically relevant positive test? What is the appropriate donor deferral? Are product recalls and withdrawals appropriate?

April Summary  Prudent measures to reduce patient exposure to alloantibodies may markedly reduce risk.  Availability issues with AB plasma and apheresis platelets argue against product gender labeling and the use of only male plasma-rich products.  Uncertainty regarding the etiology of TRALI, the lack of available antibody screening technology and a poor understanding of the role of specific antibodies prevents and argues against universal history and/or antibody screening at this time.