Plasma cytokines and markers of endothelial activation increase after packed red blood cell transfusion in the preterm infant

Abstract

Background: Transfusion of packed red blood cells (PRBcs) saves lives in the neonatal critical care setting and is one of the most common interventions in the preterm infant. The number and volume of PRBc transfusions are associated with several major neonatal morbidities, although a direct causal link between transfusion and major neonatal morbidity is still to be proven. Transfusion-related immunomodulation (TRIM) may underlie these adverse outcomes, yet it has received little attention in the high-risk preterm infant. Methods: One transfusion event was studied in infants ≤28 wk gestation between 2 and 6 wk postnatal age (n = 28). Plasma inflammatory cytokines and markers of endothelial activation were measured in the infants before and 2-4 h after transfusion, as well as in the donor pack. results: Median (range) age at transfusion was 18 (14-39) days with the pretransfusion hemoglobin level at 9.8 (7.4-10.2) g/dl. Interleukin (IL)-1β (P = 0.01), IL-8 (P = <0.001), tumor necrosis factor-α (P = 0.008), and monocyte chemoattractant protein (P = 0.01) were increased after transfusion. a similar elevation in markers of endothelial activation was seen after transfusion with increased plasma macrophage inhibitory factor (P = 0.005) and soluble intracellular adhesion molecule-1 (P = <0.001). conclusion: Production of inflammatory cytokines and immunoactivation of the endothelium observed after the transfusion of PRBcs in the preterm infant may be a manifestation of TRIM. The implications of this emerging phenomenon within the preterm neonatal population warrant further investigation. t ransfusion of blood products is not benign. In adults, transfusion is an independent predictor of death and is associated with an increased incidence of multiorgan system failure, length of hospital stay, infection risk, and modulation of the immune system (1,2). Although the mechanisms underlying these associations are yet to be comprehensively characterized, a two-hit model of posttransfusion injury has been proposed (3). In the clinical setting of an underlying inflammatory state priming the recipient's immune system, transfusion of packed red blood cells (PRBCs) may trigger immune cell activation and related immunomodulation, resulting in frank inflammation (4). This transfusion-related immunomodulation (TRIM), encompassing not only adverse proinflammatory and immunosuppressive responses but also the whole spectrum of posttransfusion effects on organs and tissues, has been proposed to underlie much of the increased transfusionassociated morbidity and mortality seen in adults (4).In the neonatal population, there is an increasing awareness of the excess morbidity and mortality associated with PRBC transfusions (5,6). PRBC transfusions have been implicated in the development of problems not encountered in the adult population, including chronic lung disease (7), retinopathy of prematurity (8), and necrotizing enterocolitis (9,10), with the incidence and severity of these conditions correlating with the number and volume of PRBC tran...

Haemostatic function and biomarkers of endothelial damage before and after RBC transfusion in patients with haematologic disease

“…1 The correlations between RBC product storage time and 1 h delta R-time (borderline significant) and 1 h delta angle respectively, indicating that increased storage time was associated with decreased change in R-time and increased change in angle. study in neonates [21]. However, at 1 h after transfusion, the levels of most endothelial biomarkers were slightly reduced (about 5%).…”

Does non-transferrin bound iron contribute to transfusion related immune-modulation in preterms?

“…Age related alterations in PRBCs that impair their ability to meet tissue oxygen needs8 33 and pro-inflammatory effects of bioactive materials that accumulate during storage7 34 have been proposed to underlie the association between PRBC transfusion and adverse clinical sequelae. Retrospective studies in adult populations have suggested that transfusion of older RBCs is associated with an increased incidence of transfusion related adverse outcomes, including sepsis, pneumonia, multi-organ failure, myocardial infarction, acute renal failure, thrombosis and mortality 35.…”

“…Further, the incidence and severity of these conditions have been reported to correlate with the number and volume of transfusions received 3 6. It has been proposed that this transfusion associated morbidity and mortality are secondary to transfusion related immunomodulation (TRIM) 7 8…”

“…However, these interventions designed to prevent TRIM have not been definitively proven to ameliorate the risk of adverse outcomes 12–14. As such, other bioactive substances which may be associated with storage related changes in red blood cells (RBCs)12–14 are likely contributors to the alterations in immune function observed following PRBC transfusion 7 12 15…”

Short-Term Effects of Blood Transfusions on Hepcidin in Preterm Infants

“…However, there might be a small direct effect of free iron as non-transferrin-bound iron, which builds up in the extracellular medium of stored packed cells [14] and is measurable in the blood of premature babies after RBC transfusion [15]. Additionally, the observed increase in Hep S could, in part, be related to the increase in inflammatory cytokine concentrations that was previously observed shortly after RBC transfusion in preterm infants [16]. Theoretically, Hep S might also increase after RBC transfusion due to ‘hepcidin transfusion' but, unfortunately, we did not measure hepcidin concentrations in the packed RBC units.…”