Aged versus fresh autologous platelet transfusion in a two-hit healthy volunteer model of transfusion-related acute lung injury

Abstract

Background: Transfusion-related acute lung injury (TRALI) is a severe complication of blood transfusion that is thought of as a two-hit event: first the underlying patient condition (e.g., sepsis), and then the transfusion. Transfusion factors include human leukocyte antigen antibodies or biologic response modifiers (BRMs) accumulating during storage. Preclinical studies show an increased TRALI risk with longer stored platelets, clinical studies are conflicting. We aim to discover whether longer platelet concentrate (PC) storage time increases TRALI risk in a controlled human experiment.

Study design and methods: In a randomized controlled trial, 18 healthy male volunteers received a first hit of experimental endotoxemia (2 ng/kg lipopolysaccharide), and a second hit of fresh (2-day old) or aged (7-day old) autologous PC, or physiological saline. After 6 h, changes in TRALI pathways were determined using spirometry, chest X-ray, and bronchoalveolar lavage (BAL).

Results: All subjects reacted adequately to lipopolysaccharide infusion and satisfied SIRS criteria (increased pulse [>90/min] and temperature [>38°C]). There were no differences between the saline, fresh, and aged PC groups in BAL-fluid protein (95 ± 33 μg/ml; 83 ± 21 μg/ml and 104 ± 29 μg/ml, respectively) and relative neutrophil count (1.5 ± 0.5%; 1.9 ± 0.8% and 1.3 ± 0.8%, respectively), nor in inflammatory BAL-fluid BRMs (Interleukin-6, CXCL8, TNFα $,$ and myeloperoxidase), clinical respiratory parameters, and spirometry results. All chest X-rays were normal.

Conclusions: In a human endotoxemia model of autologous platelet transfusion, with an adequate first hit and platelet storage lesion, transfusion of 7-day-old PC does not increase pulmonary inflammation compared with 2-day-old PC.

Keywords: autologous blood transfusion; bronchoalveolar lavage; platelet activation; platelet transfusion; transfusion-related acute lung injury.

FIGURE 1

Aged platelets were significantly more activated than fresh platelets. Platelet activation (A/B: CD62P and C/D: CD63) and apoptosis (E/F: phosphatidylserine) markers were measured after storage, after biotinylation of 50 ml platelet concentrate out of a total volume of 300–350 ml, but prior to transfusion. Markers were measured using flow cytometry. Significance levels: *p < .05; **p < .01.

FIGURE 2

All subjects reacted adequately to a first hit of lipopolysaccharide. The light gray area represents the time before transfusion, and the dark gray area represents the time after transfusion. Data were analyzed using repeated measurements analysis of variance, with an interaction term for time and treatment allocation.

FIGURE 3

Blood cell counts and inflammatory biomarkers changed after infusion of lipopolysaccharide. The light gray area represents the time before transfusion, and the dark gray area represents the time after transfusion. Data were analyzed using repeated measurements analysis of variance, with an interaction term for time and treatment allocation.

FIGURE 4

BAL‐fluid protein content and neutrophil count did not differ between groups. Boxplots show the median and interquartile ranges for bronchoalveolar lavage (BAL) fluid protein content (A) and BAL‐fluid relative neutrophil count (B). Individual measurements are shown as small dots, while group means are shown as ♦.