Jason P. Acker

Respiratory transfusion reactions represent some of the most severe adverse reactions related to receiving blood products. Of those, transfusion-related acute lung injury (TRALI) is associated with elevated morbidity and mortality. TRALI is characterized by severe lung injury associated with inflammation, pulmonary neutrophil infiltration, lung barrier leak, and increased interstitial and airspace edema that cause respiratory failure. Presently, there are few means of detecting TRALI beyond clinical definitions based on physical examination and vital signs or preventing/treating TRALI beyond supportive care with oxygen and positive pressure ventilation. Mechanistically, TRALI is thought to be mediated by the culmination of two successive proinflammatory hits, which typically comprise a recipient factor (1st hit—e.g., systemic inflammatory conditions) and a donor factor (2nd hit—e.g., blood products containing pathogenic antibodies or bioactive lipids). An emerging concept in TRALI research is the contribution of extracellular vesicles (EVs) in mediating the first and/or second hit in TRALI. EVs are small, subcellular, membrane-bound vesicles that circulate in donor and recipient blood. Injurious EVs may be released by immune or vascular cells during inflammation, by infectious bacteria, or in blood products during storage, and can target the lung upon systemic dissemination. This review assesses emerging concepts such as how EVs: 1) mediate TRALI, 2) represent targets for therapeutic intervention to prevent or treat TRALI, and 3) serve as biochemical biomarkers facilitating TRALI diagnosis and detection in at-risk patients.

Background Circulating CD71 + red blood cells (RBCs) have been reported to play an immunomodulatory role in vivo , which may contribute to adverse donor–recipient sex‐mismatched transfusion outcomes. However, it is not clear how CD71 + RBC quantity in red cell concentrates (RCCs) is affected by manufacturing methods and donor factors such as donor sex, donor age, pre‐donation hemoglobin (Hb), venous Hb (Hb v ) levels, and donation frequency. Methods We determined CD71 + RBCs and Hb levels in whole blood (WB) from healthy donors (42 male/38 female). Using small‐scale red cell filtration (RCF) and whole blood filtration (WBF) methods, leukoreduced RCCs were processed from WB samples ( n = 6) and the CD71 + RBCs were determined at days 1, 7, and 28. We examined uni‐ and multivariate associations among CD71 + RBCs, donor factors, and manufacturing method. Results Male donors had a higher CD71 + RBC concentration than females ( p < .001), especially male donors aged 17–50 years with 1 or 2 WB donations over the previous 12 months. Donors with a Hb v above 155 g/L had a higher CD71 + RBC concentration than an Hb v level below 140 g/L ( p < .05). There was a positive correlation between pre‐donation Hb and CD71 + RBC concentration (Pearson r = 0.41). WBF RCCs had a higher total number of CD71 + RBCs than RCF‐produced RCCs on day 1 ( p < .05). Discussion RCCs have variable numbers of CD71 + RBCs. This makes understanding the impact of donor factors and manufacturing methods on the immunomodulatory effect of CD71 + RBCs critical in exploring donor–recipient sex‐mismatched transfusions.