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

Abstract

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.

Fig. 1

LAPS-II timeline. Components in the control arm were matched by the donor's sex, parity, center, and time period to the components in the study arm.

Fig. 2

Flow chart of data acquisition at various stages of retrospective medical record review. CXR = chest X-ray; Tx = transfusion.

Fig. 3

Results for LAPS-II component tracing and recipient medical record review in study and control arms. Boxes indicate number of recipients progressing through each stage of data collection. Circles indicate number of recipients completing data review at each stage and provide further details about recipients not progressing to the next stage of data collection. Due to space limitations, circles are displayed on either side of the primary flow chart. Within each circle, numbers in parentheses indicate study and control arm recipients. Split components are donations that were divided into two or more components that were transfused to different LAPS-II recipients, duplicate recipients are recipients who received more than one LAPS-II component and were excluded from the study for that reason, and other component types are components that were initially classified as high-plasma-volume components but which were volume reduced before transfusion. The percentage of study arm and control arm recipients who completed data collection at various junctures of the protocol was equivalent by exact p value of likelihood ratio statistic: (a) p = 0.98 for study or control arm by posttransfusion chest X-ray or no posttransfusion chest X-ray; (b) p = 0.26 for study or control arm by pulmonary edema or no pulmonary edema; (c) p = 0.23 for study or control arm by full or partial extended review; (d) p = 0.32 for study or control arm by expert panel review or no expert panel review. CXR = chest X-ray; Tx = transfusion.

Fig. 4

HLA antibody NBG screening value and number of single-antigen bead (SAB) reactivities in LAPS-II donations that were transfused into recipients who developed TRALI or did not develop TRALI. (∎) No TRALI; (◻) TRALI. There was no significant difference (using Kruskal-Wallis test) between TRALI and non-TRALI cases for NBG signal strength or number of SAB reactivities. Of the seven study arm recipients with TRALI, one received a LAPS-II component with Class I (CLI) antibody only, three received LAPS-II components with Class II (CLII) antibody only, and three received LAPS-II components with Class I and Class II antibody.

Fig. 5

Median number of other components transfused within 6 hours of the first pulmonary finding. (∎) Plasma; (◻) all components. There was no significant difference among the three groupings (TRALI, possible TRALI, TRALI/TACO) in terms of the median number of plasma components (p = 0.11), nor in terms of the median number of all types of components (p = 0.05).