Red blood cell transfusions can induce proinflammatory cytokines in preterm infants

Dani, Carlo; Poggi, Chiara; Gozzini, Elena; Leonardi, Valentina; Sereni, Alice; Abbate, Rosanna; Gori, Anna Maria

doi:10.1111/trf.14080

Cited by 69 publications

(70 citation statements)

References 42 publications

(78 reference statements)

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“…As our recent study demonstrated that anemia alone correlated with NEC irrespective of RBC transfusion, these results guided the focus of the current study. However, given the present findings and recent studies suggesting that transfusion may also impact neonatal immune function, future studies will be needed to decipher appropriate hemoglobin thresholds and optimal transfusion protocols to reduce or prevent anemia‐induced intestinal inflammation and injury.…”

Section: Discussionmentioning

confidence: 94%

Anemia induces gut inflammation and injury in an animal model of preterm infants

et al. 2019

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BACKGROUND While very low birth weight (VLBW) infants often require multiple red blood cell transfusions, efforts to minimize transfusion‐associated risks have resulted in more restrictive neonatal transfusion practices. However, whether restrictive transfusion strategies limit transfusions without increasing morbidity and mortality in this population remains unclear. Recent epidemiologic studies suggest that severe anemia may be an important risk factor for the development of necrotizing enterocolitis (NEC). However, the mechanism whereby anemia may lead to NEC remains unknown. STUDY DESIGN AND METHODS The potential impact of anemia on neonatal inflammation and intestinal barrier disruption, two well‐characterized predisposing features of NEC, was defined by correlation of hemoglobin values to cytokine levels in premature infants and by direct evaluation of intestinal hypoxia, inflammation and gut barrier disruption using a pre‐clinical neonatal murine model of phlebotomy‐induced anemia (PIA). RESULTS Increasing severity of anemia in the preterm infant correlated with the level of IFN‐gamma, a key pro‐inflammatory cytokine that may predispose an infant to NEC. Gradual induction of PIA in a pre‐clinical model resulted in significant hypoxia throughout the intestinal mucosa, including areas where intestinal macrophages reside. PIA‐induced hypoxia significantly increased macrophage pro‐inflammatory cytokine levels, while reducing tight junction protein ZO‐1 expression and increasing intestinal barrier permeability. Macrophage depletion reversed the impact of anemia on intestinal ZO‐1 expression and barrier function. CONCLUSIONS Taken together, these results suggest that anemia can increase intestinal inflammation and barrier disruption likely through altered macrophage function, leading to the type of predisposing intestinal injury that may increase the risk for NEC.

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Section: Discussionmentioning

confidence: 94%

Anemia induces gut inflammation and injury in an animal model of preterm infants

et al. 2019

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“…Additionally, significant immunomodulation occurs in infants after transfusion of allogeneic RBCs, leading to increased expression of proinflammatory cytokines [e.g. interleukin (IL)‐1, IL‐8] and markers of endothelial activation (Keir et al , ; Dani et al , ). Studies have shown that continuation of enteral feed during RBC transfusion blunts post‐prandial mesenteric hyperaemia for up to 48 h after transfusion (Marin et al , ).…”

Section: When Do We Give Rbc Transfusions For Anaemia Of Prematurity?mentioning

confidence: 99%

Management of anaemia in pre‐term infants

Saito-Benz

Flanagan²,

Berry

2019

Br J Haematol

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Pre-term infants have one of the highest transfusion requirements within the hospital-setting. The vast majority of blood transfusions performed in Neonatal Intensive Care Units (NICUs) are for medically stable pre-term infants with anaemia of prematurity, with the aim of improving oxygen delivery to the vital organs during the crucial phase of growth and development. However, despite the frequency of transfusion in this population, the potential benefits and harms of 'top up' transfusion are not fully understood, leading to practice variation between clinicians, institutions and countries. Significant advances have been made in the prevention of anaemia of prematurity, with recent emphasis on optimising infants' circulatory volume at birth via placental transfusion and preserving infants' own blood volume through innovative minimal sampling techniques. More research is urgently needed to establish optimal transfusion thresholds for these high-risk pre-term infants, for whom benefits as well as adverse outcomes may have consequences that extend for decades throughout the recipients' life-course. In this review, we will discuss some of the consensus and controversies regarding optimal management of anaemia in pre-term infants and highlight potential areas for future research.

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“…Dani et al [76] prospectively examined 20 infants with a gestational age < 32 weeks and measured serum levels of various cytokines before and at various time points after RBCT up to 48 h post-RBCT. That small study showed a significant increase in IL-1β, IL-8, IFN-γ, IL-17, MCP-1, IP-10, and ICAM-1 after RBCT.…”

Section: Anaemia Blood Transfusion and Necmentioning

confidence: 99%

Red Blood Cell Transfusion in Preterm Infants: Current Evidence and Controversies

2018

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The current evidence regarding the indication, advantages and risks of red blood cell transfusion (RBCT) for preterm infants is discussed. This is an important area in Neonatology to be examined given that 90% of extremely low birth weight infants receive RBCT and many controversies remain regarding when to transfuse and the risks of RBCT. The various treatment thresholds and guidelines used are presented and we compare the short-term clinical benefits of liberal and restrictive RBCT in preterm infants; the majority of these are equivocal and sadly long-term outcome data is limited. The latest evidence on how anaemia and blood transfusion affect organ perfusion in preterm infants is presented. This is important when trying to establish the optimal trigger threshold for RBCT in preterm infants, especially because the knowledge about the adaptive physiological responses to anaemia in very low birth weight infants and the effects of RBCT at various levels of anaemia is also inadequate. Further research into the physiological adaptive response to anaemia of varying degrees and to RBCT at different levels of anaemia in preterm infants of different gestational and post-natal ages is needed before we can conclusively guide the optimal timing and trigger thresholds for RBCT in preterm infants.

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Red blood cell transfusions can induce proinflammatory cytokines in preterm infants

Cited by 69 publications

References 42 publications

Anemia induces gut inflammation and injury in an animal model of preterm infants

Anemia induces gut inflammation and injury in an animal model of preterm infants

Management of anaemia in pre‐term infants

Red Blood Cell Transfusion in Preterm Infants: Current Evidence and Controversies

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