Amy Keir

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

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.

A systematic review of transfusion-associated graft-versus-host disease.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication of blood transfusion. The clinicolaboratory features of TA-GVHD and the relative contributions of recipient and component factors remain poorly understood. We conducted a systematic review of TA-GVHD reports. The HLA relationship between donor and recipient was classified as D = 0 when no donor antigens were foreign to the recipient vs D ≥ 1 when ≥1 donor antigen disparity occurred. We identified 348 unique cases. Criteria for component irradiation were met in 48.9% of cases (34.5% immune-compromised, 14.4% related-donor), although nonirradiated components were transfused in the vast majority of these (97.6%). Components were typically whole blood and red cells. When reported, component storage duration was ≤10 days in 94%, and 23 (6.6%) were leukoreduced (10 bedside, 2 prestorage, and 11 unknown). Among 84 cases with HLA data available, the category of D = 0 was present in 60 patients (71%) at either HLA class I or II loci and was more common among recipients without traditional indications for component irradiation. These data challenge the historic emphasis on host immune defects in the pathogenesis of TA-GVHD. The dominant mechanism of TA-GVHD in both immunocompetent and compromised hosts is exposure to viable donor lymphocytes not recognized as foreign by, but able to respond against, the recipient.

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

Objective There is increasing awareness that allogeneic transfusion is potentially harmful in preterm neonates secondary to transfusion related immunomodulation (TRIM). Non-transferrin bound iron (NTBI) may contribute to TRIM by promoting oxidative damage and pro-inflammatory cytokine release. The current study aimed to determine if transfusion early in the neonatal period resulted in an increase in circulating NTBI, oxidative stress and immune activation. Design Prospective observational study. Setting One transfusion event was studied in infants ≤28 weeks gestation between 2 and 6 weeks postnatal age (n=33) admitted to a tertiary neonatal intensive care unit. Methods Serum NTBI, inflammatory cytokines and malondialdehyde (MDA) were measured from the donor pack, prior to and at 2–4 and 24 h post-transfusion. Results Median (range) age at transfusion was 17 (14–39) days with the pretransfusion haemoglobin level 9.6 (7.4–10.4) g/dl. NTBI was detectable in 18 (51%) of the transfusion packs. NTBI levels were higher after transfusion (p<0.01) returning to pretransfusion levels by 24 h. Post-transfusion NTBI level correlated with the age of transfused blood (p<0.001) and was positively correlated with plasma MDA (p=0.01) but not IL-1β, IL-6, IL8 or TNFα. Conclusions Circulating NTBI is transiently elevated following blood transfusion in preterm newborns. This increase was related to the age of blood transfused and correlated with increases in oxidative stress but not pro-inflammatory cytokines. While further studies are necessary to determine whether these transient effects influence clinical outcome, the current data do not support a significant role in the very preterm neonate for NTBI in TRIM.

Beyond the borderline: Outcomes for inborn infants born at ≤500 grams

To report survival, morbidity and neurodevelopmental outcome in a cohort of extremely low birthweight infants.

Question 1 * do feeding practices during transfusion influence the risk of developing necrotising enterocolitis in preterm infants?

An otherwise well 4-week-old 28-week gestation male infant has a haemoglobin level of 69 g/l associated with a low reticulocyte count. He is currently on full enteral feeds. The medical plan is to give him a blood transfusion, but the nursing staff ask whether feeding should be stopped around the time of transfusion to reduce his chance of developing complications. What is the evidence that feeding practices during transfusion influence the risk of developing transfusion-associated necrotising enterocolitis (TANEC)? In a preterm infant [patient] with anaemia of prematurity, do feeding practices [intervention] during blood transfusion reduce the risk of developing TANEC [outcome]? MEDLINE (1966–2012), SUMsearch2, the Cochrane library and the Pediatric Academic Societies abstract archive (2000–2011) were searched using the terms: infant, newborn infant, preterm AND necrotising enterocolitis AND transfusion AND feeding, limited to human biology and paediatric population where possible. A total of 342 articles were identified, of which …

Communication skills training in paediatrics

A discussion of the importance of clear and sensitive communication by all members of the medical profession is followed by an examination of how those who train paediatricians can best teach the skills necessary to their trainees.

How to use: the direct antiglobulin test in newborns

The direct antiglobulin test (DAT) detects the presence of immunoglobulin, complement or both bound to the red blood cell membrane. The test, historically called the ‘Coombs test’, was first described in 1945 by Cambridge immunologist Robin Coombs. Suspected haemolytic disease of the newborn, due to either Rhesus disease or ABO incompatibility, is one of most common reasons for requesting a DAT in newborns. In this article, we discuss the physiological background and technological background of the DAT. We also provide a clinical framework for a rational approach to the use and interpretation of the DAT in newborns.

Neonatal Plasma Transfusion: An Evidence-Based Review

Several clinical scenarios for plasma transfusion are repeatedly identified in audits, including treatment of bleeding in association with laboratory evidence of coagulopathy, correction of disseminated intravascular coagulation, prevention of intraventricular hemorrhage, management of critically ill neonates (eg, during sepsis or as a volume expander), or correction of markers of prolonged coagulation in the absence of bleeding. The findings of at least one national audit of transfusion practice indicated that almost half of plasma transfusions are given to neonates with abnormal coagulation values with no evidence of active bleeding, despite the limited evidence base to support the effectiveness of this practice. Plasma transfusions to neonates should be considered in the clinical context of bleeding (eg, vitamin K dependent), disseminated intravascular coagulation, and very rare inherited deficiencies of coagulation factors. There seems to be no role for prophylactic plasma to prevent intraventricular hemorrhage or for use as a volume expander.

Fresh-frozen plasma should not be given to nonbleeding premature infants with "abnormal" coagulation tests.

We read with interest the recent study by Dani and colleagues describing a reduction in risk of developing retinopathy of prematurity (ROP) in premature infants who received two or more transfusions of fresh-frozen plasma (FFP) within the first week of life. The authors do not go so far as to suggest the use of early FFP to prevent ROP and state “the use of FFP for this purpose cannot be recommended.” Presumably this is a hypothesis-generating study but it is concerning that no discussion regarding the evidence base for use of FFP in premature infants is included. An unclear proportion of infants in the study received FFP after they were found to have “abnormal” coagulation tests (without active bleeding) taken within 2 hours of birth with others receiving FFP only if active bleeding occurred. It is this use of FFP as “prophylaxis” that is of most concern. A recent prospective observational study also published in TRANSFUSION demonstrated abnormal coagulation values at birth do not predict bleeding during the first week in premature infants. The authors of this study bring into question the value of coagulation screening of nonbleeding premature infants and use of prophylactic FFP in those with abnormal values. Evidence from randomized controlled trials does not support this prophylactic use of FFP in premature infants to improve either short-term or long-term outcomes. Despite this lack of evidence for its use, FFP remains a relatively common blood product transfused to premature infants. Retrospective studies are vulnerable to many methodologic problems including confirmation bias, unblinded assessment, and publication bias as well as confounding. Caution must be exercised when drawing conclusions from retrospective studies. A recent example of this is the increasingly common practice of withholding milk feeds during red blood cell transfusion with the theoretical aim to reduce the risk of necrotizing enterocolitis in premature infants based on limited evidence. While this study by Dani and colleagues describes an interesting association, it is no more than that. It is likely the authors did not intend for broader practice implications to be drawn from their study but in our desire to improve the outcomes of premature infants, some readers may. Careful consideration must be given before transfusing any blood product to a premature infant when the highest level of evidence available does not support it. CONFLICT OF INTEREST

Coinfusion of dextrose-containing fluids and red blood cells does not adversely affect in vitro red blood cell quality.

Transfusion guidelines advise against coinfusing red blood cells (RBCs) with solutions other than 0.9% saline. We evaluated the impact of coinfusion with dextrose‐containing fluids (DW) on markers of RBC quality.