Transfusion with washed packed red blood cells (PRBCs) may be associated with reduced transfusion‐related pro‐inflammatory cytokine production. This may be because of alterations in recipient immune responses.

This randomised trial evaluated the effect of transfusion with washed compared with unwashed PRBCs on pro‐inflammatory cytokines and endothelial activation in 154 preterm newborns born before 29 weeks’ gestation. Changes in plasma cytokines and measures of endothelial activation in recipient blood were analysed after each of the first three transfusions.

By the third transfusion, infants receiving unwashed blood had an increase in IL‐17A (P = 0.04) and TNF (P = 0.007), whereas infants receiving washed blood had reductions in IL‐17A (P = 0.013), TNF (P = 0.048), IL‐6 (P = 0.001), IL‐8 (P = 0.037), IL‐12 (P = 0.001) and IFN‐γ (P = 0.001). The magnitude of the post‐transfusion increase in cytokines did not change between the first and third transfusions in the unwashed group but decreased in the washed group for IL‐12 (P = 0.001), IL‐17A (P = 0.01) and TNF (P = 0.03), with the difference between the groups reaching significance by the third transfusion (P < 0.001 for each cytokine).

The pro‐inflammatory immune response to transfusion in preterm infants can be modified when PRBCs are washed prior to transfusion. Further studies are required to determine whether the use of washed PRBCs for neonatal transfusion translates into reduced morbidity and mortality.

• immunomodulation
• preterm
• red blood cells
• transfusion

Patients with hereditary hemochromatosis and non-transfusion-dependent hereditary anemia develop predominantly liver iron-overload. We present a unique method allowing quantification of liver iron retention in humans during first-pass of ⁵⁹Fe-labeled iron through the portal system, using standard ferrokinetic techniques measuring red cell iron uptake after oral and intravenous ⁵⁹Fe administration. We present data from patients with iron deficiency (ID; N = 47), hereditary hemochromatosis (HH; N = 121) and non-transfusion-dependent hereditary anemia (HA; N = 40). Mean mucosal iron uptake and mucosal iron transfer (±SD) were elevated in patients with HH (59 ± 18%, 80 ± 15% respectively), HA (65 ± 17%, 74 ± 18%) and ID (84 ± 14%, 94 ± 6%) compared to healthy controls (43 ± 19%, 64 ± 18%) (p < 0.05) resulting in increased iron retention after 14 days compared to healthy controls in all groups (p < 0.01). The fraction of retained iron utilized for red cell production was 0.37 ± 0.17 in untreated HA, 0.55 ± 0.20 in untreated HH and 0.99 ± 0.22 in ID (p < 0.01). Interestingly, compared to red blood cell iron utilization after oral iron administration, red blood cell iron utilization was higher after injection of transferrin-bound iron in HA and HH. Liver iron retention was considerably higher in HH and HA compared to ID. We hypothesize that albumin serves as a scavenger of absorbed Fe(II) for delivering albumin-bound Fe(III) to hepatocytes.

• NTBI 3
• hemochromatosis 1
• hereditary anemia 4
• iron 2
• iron deficiency 5

• Administration, Intravenous
• Administration, Oral
• Adolescent
• Adult
• Aged
• Anemia, Hemolytic, Congenital/drug therapy
• Anemia, Hemolytic, Congenital/metabolism
• Anemia, Iron-Deficiency/drug therapy
• Anemia, Iron-Deficiency/metabolism
• Case-Control Studies
• Female
• Hemochromatosis/drug therapy
• Hemochromatosis/metabolism
• Humans
• Iron Radioisotopes/administration & dosage
• Iron Radioisotopes/pharmacokinetics
• Liver/chemistry
• Male
• Middle Aged
• Serum Albumin, Human/metabolism
• Transferrin/metabolism
• Young Adult

• Oxidative damage
• Trolox
• red blood cell
• sodium ascorbate (vitamin C)
• storage

• red blood cells
• transfusion
• macrophages
• cytokines
• non-transferrin bound iron

• Animals
• Blood Preservation/adverse effects
• Blood Preservation/methods
• Erythrocyte Transfusion
• Erythrocytes/physiology
• Hemolysis/physiology
• Humans
• Immunity/physiology
• Infections/blood
• Infections/transmission
• Inflammation/blood
• Iron/blood

• K08 HL103756 NHLBI NIH HHS
• R01 HL098014 NHLBI NIH HHS
• R01 HL115557 NHLBI NIH HHS
• R01 HD115557 NICHD NIH HHS

Many premature babies, especially those with a low birth weight are given multiple transfusions during their first few weeks of life. The major serious complications of prematurity include bronchopulmonary dysplasia, with lesser incidences of retinopathy of prematurity, intraventricular haemorrhage, and necrotising enterocolitis. Many studies have shown correlations between the receipt of blood transfusions and the development of these conditions, but little is known of the underlying pathophysiology of this relationship. Recent studies are beginning to provide some answers. This review examines recent findings with regard to the influence of preparation and storage of paediatric packed red blood cell units on heme, iron, and oxidative status of the units and relates these to the ability of the premature baby to deal with these changes following the receipt of blood transfusions. Paediatric packed red blood cell units are a potential source of heme, redox active iron and free radicals, and this increases with storage age. Haemolysis of transfused red blood cells may add further iron and cell free haemoglobin to the recipient baby. Premature babies, particularly those with low birth weight and gestational age appear to have little reserve to cope with any additional iron, heme and/or oxidative load. The consequences of these events are discussed with regard to their contribution to the major complications of prematurity and a novel hypothesis regarding transfusion-related morbidity in premature babies is presented. The review concludes with a discussion of potential means of limiting transfusion related iron/heme and oxidative load through the preparation and storage of packed red blood cell units and through modifications in clinical practice.

• Blood transfusions
• Premature babies
• Iron
• Heme
• Oxidative stress
• Storage lesion
• Complications of prematurity