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

Abstract

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.

img1

img2

Figure 1

LAPS enrollment figures and distribution of donors by gender, transfusion, and pregnancy history. Targeted enrollment was used to enroll sufficient numbers of transfused male donors.

Figure 2

HLA antibody prevalence for class I, class II, class I and II and any HLA antibody at a 3SD cutoff in transfused and non-transfused males. The difference in HLA antibody prevalence was not statistically significant (p=0.16).

Figure 3

HLA antibody prevalence for class I, class II, class I and II and to any HLA antibody at a 3SD cutoff in never pregnant women and women with one or more pregnancies is shown. There is a statistically significant increase in the prevalence of class I, class II or any HLA antibody with an increasing number of pregnancies, from one to four or more (overall trend p<.0001). The first two pregnancies were associated with the greatest increase in prevalence of HLA antibodies.

Figure 4

Box plot of the distribution of the observed HLA class I NBG values above the cutoff of 10.8 in each donor group. The distribution of NBG values observed in transfused males, non-transfused males and never pregnant females is similar. Higher NBG values are seen in women with 2 or more pregnancies compared to women with one pregnancy.