Adverse reactions and other factors that impact subsequent blood donation visits.

BACKGROUND: The importance of adverse reactions in terms of donor safety recently has received significant attention, but their role in subsequent donation behavior has not been thoroughly investigated. STUDY DESIGN AND METHODS: Six REDS-II blood centers provided data for this analysis. Summary minor and major adverse reaction categories were created. The influence of adverse reactions on donation was examined in two ways: Kaplan-Meier curves were generated to determine the cumulative pattern of first return, and adjusted odds ratios (AORs) for demographic and other factors positively and negatively associated with return were estimated using multivariable logistic regression. RESULTS: Donors who had major reactions had longer times to return than donors with minor or no reactions. The AOR of returning for donors with major reactions was 0.32 (95% confidence interval [CI], 0.28-0.37) and with minor reactions 0.59 (95% CI, 0.56-0.62) when compared to donors who did not have reactions. Conversely, the most important factors positively associated with return were the number of donations in the previous year and increasing age. Subsequent return, whether a major, minor, or no reaction occurred, varied by blood center. Factors that are associated with the risk of having adverse reactions were not substantial influences on the return after adverse reactions. CONCLUSION: Having an adverse reaction leads to significantly lower odds of subsequent donation irrespective of previous donation history. Factors that have been associated with a greater risk of adverse reactions were not important positive or negative predictors of return after a reaction.

The frequency and specificity of human neutrophil antigen antibodies in a blood donor population.

BACKGROUND: Transfusion-related acute lung injury (TRALI) has been associated with both human leukocyte antigen (HLA) and human neutrophil antigen (HNA) antibodies. HNA antibody frequency, specificity, and demographic associations have not been well defined in the blood donor population. STUDY DESIGN AND METHODS: A subset of 1171 donors (388 nontransfused males, 390 HLA antibody-negative females with three or more pregnancies, and 393 HLA antibody-positive females with three or more pregnancies) from a larger Leukocyte Antibody Prevalence Study was tested for immunoglobulin (Ig)G and IgM HNA antibody using a granulocyte immunofluorescence flow cytometry assay. Additional testing on selected samples included monoclonal antibody immobilization of granulocyte antigen-flow cytometry and granulocyte genotyping. RESULTS: Eight samples were HNA antibody positive (prevalence, 0.7%; 95% confidence interval [CI], 0.3%-1.3%]). Three HNA antibodies (one IgG and two IgM) were found in nontransfused males (prevalence, 0.8%; 95% CI, 0.2%-2.2%); all were panreactive or nonspecific. One HLA antibody-negative previously pregnant female had an IgG HNA antibody with HNA-1a specificity (prevalence, 0.3%; 95% CI, 0.01%-1.4%). Four HLA antibody-positive previously pregnant females demonstrated HNA antibodies, three IgG and one IgM (prevalence, 1%; 95% CI, 0.3%-2.6%). Two of these were HNA-1a specific, one HNA-4a specific, and one nonspecific. CONCLUSIONS: HNA antibodies occur with low frequency in the donor population and are present in both male and female donors. Despite the implementation of TRALI reduction strategies, HNA antibodies are still present in donor blood products. Although our data do not create a case for urgent implementation of donor HNA antibody testing, future new developments for high-throughput HNA antibody screening, including for HNA-3a, may warrant reconsideration.

Blood donations from previously transfused or pregnant donors: a multicenter study to determine the frequency of alloexposure.

BACKGROUND: Transfusion-related acute lung injury (TRALI) mitigation strategies include the deferral of female donors from apheresis platelet (PLT) donations and the distribution of plasma for transfusion from male donors only. We studied the implications of these policies in terms of component loss at six blood centers in the United States. STUDY DESIGN AND METHODS: We collected data from allogeneic blood donors making whole blood and blood component donations during calendar years 2006 through 2008. We analyzed the distribution of donations in terms of the sex, transfusion and pregnancy histories, and blood type. RESULTS: A TRALI mitigation policy that would not allow plasma from female whole blood donors to be prepared into transfusable plasma components would result in nearly a 50% reduction in the units of whole blood available for plasma manufacturing and would decrease the number of type AB plasma units that could be made from whole blood donations by the same amount. Deferral of all female apheresis PLT donors, all female apheresis PLT donors with histories of prior pregnancies, or all female apheresis PLT donors with histories of prior pregnancies and positive screening test results for antibodies to human leukocyte antigens (HLAs) will result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations, respectively. CONCLUSION: A TRALI mitigation policy that only defers female apheresis PLT donors with previous pregnancies and HLAs would result in an approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate a large proportion of components that are associated with TRALI.

The Leukocyte Antibody Prevalence Study-II (LAPS-II): a retrospective cohort study of transfusion-related acute lung injury in recipients of high-plasma-volume human leukocyte antigen antibody-positive or -negative components.

BACKGROUND: We used a multicenter retrospective cohort study design to evaluate whether human leukocyte antigen (HLA) antibody donor screening would reduce the risk of transfusion-related acute lung injury (TRALI) or possible TRALI. STUDY DESIGN AND METHODS: In the Leukocyte Antibody Prevalence Study-II (LAPS-II), we evaluated pulmonary outcomes in recipients of 2596 plasma-rich blood components (transfusable plasma and plateletpheresis) sent to participating hospitals; half of the components were collected from anti-HLA-positive donors (study arm) and half from anti-HLA-negative donors (control arm) matched by sex, parity, and blood center. A staged medical record review process was used. Final recipient diagnosis was based on case review by a blinded expert panel of pulmonary or critical care physicians. RESULTS: TRALI incidence was 0.59% (seven cases) in study arm recipients versus 0.16% (two cases) in control arm recipients for an odds ratio (OR) of 3.6 (95% confidence interval [CI], 0.7-17.4; p = 0.10). For possible TRALI cases (nine study arm, eight control arm), the OR was 1.2 (95% CI, 0.4-3.0; p = 0.81), and for TRALI and possible TRALI aggregated together, it was 1.7 (95% CI, 0.7-3.7; p = 0.24). Transfusion-associated circulatory overload incidence was identical in the two arms (1.17 and 1.22%, respectively; OR, 1.0; p = 1.0). CONCLUSIONS: TRALI incidence in recipients of anti-HLA-positive components was relatively low for a lookback study (1 in 170) and was higher than in the control arm, but did not reach significance. Based on this trend, the data are consistent with the likelihood that TRALI risk is decreased by selecting high-volume plasma components for transfusion from donors at low risk of having HLA antibodies.

Prevalence of HLA antibodies in remotely transfused or alloexposed volunteer blood donors.

BACKGROUND: HLA antibody testing of previously transfused or pregnant donors may help reduce the risk of transfusion-related acute lung injury (TRALI). However, the prevalence of HLA antibodies in transfused donors has not been well characterized. STUDY DESIGN AND METHODS: Transfusion and pregnancy history was obtained from consenting donors. HLA Class I and II antibody testing was performed by multiantigen bead Luminex platform. Cutoff values for Class I and II antibodies used normalized background ratios of 10.8 and 6.9, respectively. Linear probability models were used to evaluate potential associations between HLA alloimmunization and donor characteristics. RESULTS: A total of 7920 donors (2086 males and 5834 females) were tested. HLA antibody prevalence did not significantly differ between 895 transfused (1.7%) and 1138 nontransfused males (1.0%; odds ratio [OR], 1.75; 95% confidence interval [CI], 0.80-3.82]. Prevalence in 45 transfused nulliparous females (4.4%; 95% CI, 0.1%-11.8%) was not different from the 1.6% prevalence in 1732 nontransfused nulliparous females (OR, 2.94; 95% CI, 0.68-12.74). Transfused parous females had higher prevalence than nontransfused counterparts (p = 0.004; OR, 1.39; 95% CI, 1.07-1.80). In a linear probability model, the estimated additive risk of transfusion-induced alloimmunization was only 0.8% (95% CI, -0.2% to 1.8%; p = 0.10). Donor transfusion history showed that 58% of transfusions occurred more than 10 years previously. CONCLUSION: Transfused volunteer blood donors do not appear to have a significantly higher prevalence of HLA antibodies than their nontransfused counterparts. Thus, in an effort to reduce TRALI risk, ascertaining past history of transfusion and testing these donors for HLA antibodies is not necessary.

The effect of previous pregnancy and transfusion on HLA alloimmunization in blood donors: implications for a transfusion-related acute lung injury risk reduction strategy.

BACKGROUND: Antibodies to human leukocyte antigens (HLA) in donated blood have been implicated as a cause of transfusion-related acute lung injury (TRALI). A potential measure to reduce the risk of TRALI includes screening plateletpheresis donors for HLA antibodies. The prevalence of HLA antibodies and their relationship to previous transfusion or pregnancy in blood donors was determined. STUDY DESIGN AND METHODS: A total of 8171 volunteer blood donors were prospectively recruited by six US blood centers from December 2006 to May 2007. Donors provided a detailed history of pregnancy and transfusion and a sample for HLA Class I and II antibody testing by multiantigen bead flow analysis. RESULTS: A total of 8171 donors were enrolled; 7920 (96.9%) had valid HLA antibody test results and 7841 (99%) of those had complete pregnancy and transfusion information. The prevalence of any HLA antibody was similar in nontransfused (n = 1138) and transfused (n = 895) men, 1.0% versus 1.7% (p = 0.16). HLA antibodies were detected in 17.3% of all female donors (n = 5834) and in 24.4% of those with a 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.