Packed red blood cell transfusion in preterm infants.

Premature infants commonly receive adult packed red blood cells (pRBCs) during their hospital stay. As adult erythrocytes differ substantially from those of preterm infants, transfusion of adult pRBCs into preterm infants can be considered inappropriate for the physiology of a preterm infant. An absence of standardisation of transfusion protocols makes it difficult to compare and interpret pertinent clinical data, as reflected by unclear associations between pRBC transfusion and complications related to prematurity, such as bronchopulmonary dysplasia, neurodevelopmental impairment, retinopathy of prematurity, or necrotising enterocolitis. The difficulty in interpreting clinical data is further increased by differences in study designs that either overestimate pRBC-associated complications of prematurity or have not yet been designed to directly link pRBC transfusions to their respective complications. Thus, neonatal transfusion practice has become an ongoing difficulty, in which differences in transfusion guidelines hinder the ability to generate comparable clinical data, and heterogeneity in clinical data prevents the implementation of standardised transfusion protocols. To overcome these issues, novel approaches with biochemical-clinical translational designs could enable clinicians to gather causal evidence instead of circumstantial correlation.

Redox Properties of Human Erythrocytes Are Adapted for Vitamin C Recycling.

Ascorbic acid (AA; or vitamin C) is an important physiological antioxidant and radical scavenger. Some mammalian species, including homo sapiens, have lost the ability to synthetize AA and depend on its nutritional uptake. Erythrocytes from AA-auxotroph mammals express high amounts of the glucose transporter GLUT1. This isoform enables rapid uptake of glucose as well as dehydroascorbate (DHA), the fully oxidized form of AA. Here, we explored the effects of DHA uptake on the redox metabolism of human erythrocytes. DHA uptake enhanced plasma membrane electron transport (PMET) activity. This process is mediated by DCytb, a membrane bound cytochrome catalyzing extracellular reduction of Fe3+ and ascorbate free radical (AFR), the first oxidized form of AA. DHA uptake also decreased cellular radical oxygen species (ROS) levels. Both effects were massively enhanced in the presence of physiological glucose concentrations. Reduction of DHA to AA largely depleted intracellular glutathione (GSH) and induced the efflux of its oxidized form, GSSG. GSSG efflux could be inhibited by MK-571 (IC 50 = 5 µM), indicating involvement of multidrug resistance associated protein (MRP1/4). DHA-dependent GSH depletion and GSSG efflux were completely rescued in the presence of 5 mM glucose and, partially, by 2-deoxy-glucose (2-DG), respectively. These findings indicate that human erythrocytes are physiologically adapted to recycle AA both intracellularly via GLUT1-mediated DHA uptake and reduction and extracellularly via DCytb-mediated AFR reduction. We discuss the possibility that this improved erythrocyte-mediated AA recycling was a prerequisite for the emergence of AA auxotrophy which independently occurred at least twice during mammalian evolution.