The AABB recommended to its constituency to take actions to mitigate TRALI by minimizing the distribution of high-plasma-volume blood components from donors who are potentially alloimmunized to WBCs by November 2008.5
Data on the prevalence of risk factors for WBC alloimmunization are needed to assess the extent of blood component losses associated with this policy. This study provides large-scale data on the frequency of risk factors for alloimmunization to WBC antigens among US blood donors from six geographically dispersed blood centers that are part of the REDS-II studies. It also allowed us to estimate the potential loss of blood products under different TRALI mitigation strategies.
Women accounted for 49.9% of whole blood donations and 37.1% of apheresis PLT donations at the six REDS-II centers. Whole blood donations are manufactured into plasma-rich components such as fresh-frozen plasma (FFP) and cryopoor plasma. Based on our data, we estimate that a policy for TRALI mitigation that would not allow plasma from whole blood donations from women to be prepared into transfusable plasma components would result in a 50% reduction in the number of the units of whole blood available for plasma manufacturing and would decrease the number of AB blood type plasma units made from whole blood by the same amount. While it may be possible to compensate for the loss of all female-derived transfusable plasma units, the loss of all apheresis PLTs from female donors would impact clinical care. Thus, alternative ways to eliminate PLTs units most likely to cause TRALI must be found.
Previous transfusions are a possible cause of WBC alloimmunization in blood donors. Our study revealed that between the 2006 through 2008 calendar years 3% to 4% of donors reported a history of a prior transfusion. In a previous study from the REDS-I that used data collected from 1991 to 2000, 4.9% of donations were made by donors with a history of a transfusion.6
However, the deferral of transfused blood donors is not considered to be an effective TRALI mitigation strategy since the prevalence of HLA antibodies among blood donors seems to be independent of the history of prior transfusions. According to another publication from the LAPS-I study, the prevalence of positive screening tests for HLA antibodies among blood donors is not significantly different between transfused men and nontransfused men and between transfused nulliparous women and nontransfused nulliparous women.7
Blood transfusions, when received many years ago as was the case in our donor population, do not seem to produce HLA antibodies that are detectable years later, and screening donors for a history of a prior transfusion does not appear to be an effective TRALI mitigation strategy based on LAPS-I data.
Pregnancy is another risk factor for HLA and/or HNA antibody formation. Before the primary LAPS-I publication,3
published data on the history of pregnancy in blood donors were limited. In a small study from the United States, a history of one or more pregnancies was obtained in 38.2% of 322 female apheresis PLTs donors.8
A more recent study of the pregnancy history of blood donors at a US hospital-based donation program revealed that 52.6% of 1009 female whole blood or apheresis PLTs donors had been pregnant.9
Using data from donations made to the REDS-II blood centers during calendar years 2006 through 2008, we report that 66.7% of 95,000 donations of apheresis PLTs from female donors were donated by women reporting a history of one or more pregnancies.
We used data from our study to estimate the impact of three different TRALI mitigation strategies for female apheresis PLT donors. REDS-II centers collect approximately 7.0% of the whole blood donations and 8.1% of the apheresis PLT donations of the United States and donors at the REDS-II centers were assumed to be representative of donors giving blood at other centers across the United States. One potential strategy would be the deferral of all female donors from future apheresis PLT donations. The most significant benefit from this policy would be a potential substantial reduction in the cases of TRALI. In the United Kingdom, where plasma for transfusion is now predominately manufactured from male donors, the risk for highly likely or probable TRALI cases has been reduced from 15.5 cases per 1 million units of FFP issued in 1999 through 2004 (when both male and female plasma was transfused) to 3.2 cases per 1 million units of FFP issued per year in 2005 through 2006,10
and the number of TRALI cases by year of transfusion has decreased from 32 cases in 2002 (before the introduction of preferential male plasma in late 2003) to 14 cases in 2009.11
Deferring all women from apheresis PLT donations could potentially have a similar effect on the incidence of TRALI. However, this approach may also result in an unacceptably high loss of more than one-third of apheresis PLT donations (37%).
An alternative policy that would only defer female donors who had at least one prior pregnancy could result in the loss of approximately one-fourth of the apheresis PLT donations (23%). In contrast, a deferral of previously pregnant apheresis PLT donors with HLA antibodies could limit this loss to an estimated 5% of all apheresis PLT donations. While these last two strategies would less severely impact the supply of apheresis PLTs than the deferral of all female donors, blood collection agencies would nonetheless still have to replace the 5% shortfall in PLT products either by increasing the production of PLT concentrates from whole blood or by replacing the deferred female apheresis donors with male donors, with never-pregnant female donors, or with ever-pregnant female donors without HLA antibodies.
We do not believe that the results of this study are affected by selection bias since the donors provided the demographic information on pregnancy and transfusion histories without any knowledge of the subject matter being studied. We had complete information on required demographic factors needed to accept a person for a blood donation (such as age, sex, donation type, and procedure type) from every donor and nearly complete information of the pregnancy and transfusion histories of the donors who agreed to provide that information. Therefore, the degree of information bias in the study should be small. We did not have data on the pregnancy and transfusion history of donors who were recently pregnant or transfused since donors who were transfused during a 12-month period before a blood donation attempt or were pregnant at the time of a donation attempt were deferred from donating blood. We did not include the potential donation losses from donors with HNA antibodies since the prevalence of HNA antibodies among blood donors is small in comparison to the number of donors with HLA antibodies.12
We found similar distributions of donations in terms of sex, transfusion histories, pregnancy histories, and blood type among donors of whole blood and apheresis PLTs among the six REDS-II blood centers and more variability in the blood types of the donors of apheresis plasma. It could be the case that other blood collection agencies will have a different distribution of donations in terms of sex, transfusion histories, pregnancy histories, and blood type and that percentage of components lost by other blood centers from donors deferred for being potentially alloimmunized to WBC antigens is different from the percentage of components lost by our centers. Therefore, each blood collection agency needs to study its donor base to determine which TRALI mitigation strategy is best suited to provide blood components for its customers.
In summary, a TRALI mitigation strategy that only defers previously pregnant female donors with HLA and/or HNA antibodies from making apheresis PLT donations would result in an approximately 5% decrease in the apheresis PLT inventory. Since 65% cases of TRALI (according to the UK SHOT Study10
) are estimated to be related to the presence of HLA antibodies in transfused components, such a strategy would be expected to reduce the risk of TRALI.