Reference ranges of thromboelastometry in healthy full-term and pre-term neonates.

BACKGROUND: Rotational thromboelastometry (ROTEM) is an attractive method for rapid evaluation of hemostasis in neonates. Currently, no reference values exist for ROTEM assays in full-term and pre-term neonates. Our aim was to establish reference ranges for standard extrinsically activated ROTEM assay (EXTEM) in arterial blood samples of healthy full-term and pre-term neonates. METHODS: In the present study, EXTEM assay was performed in 198 full-term (≥37 weeks' gestation) and 84 pre-term infants (<37 weeks' gestation) using peripheral arterial whole blood samples. RESULTS: Median values and reference ranges (2.5th and 97.5th percentiles) for the following main parameters of EXTEM assay were determined in full-term infants: clotting time (seconds), 41 (range, 25.9-78); clot formation time (seconds), 70 (range, 40-165.2); maximum clot firmness (mm), 66 (range, 41-84.1); lysis index at 60 min (LI60, %), 97 (range, 85-100). The only parameter with a statistically significant difference between full-term and pre-term neonates was LI60 (p=0.006). Furthermore, it was inversely correlated with gestational age (p=0.002) and birth weight (p=0.016) in pre-term neonates. CONCLUSIONS: In conclusion, an enhanced fibrinolytic activity in pre-term neonates was noted. For most EXTEM assay parameters, reference ranges obtained from arterial newborn blood samples were comparable with the respective values from studies using cord blood. Modified reagents, small size samples, timing of sampling, and different kind of samples might account for any discrepancies among similar studies. Reference values hereby provided can be used in future studies.

Donor variation effect on red blood cell storage lesion: a multivariable, yet consistent, story.

BACKGROUND: Previous studies have shown that baseline hematologic characteristics concerning or influencing red blood cell (RBC) properties might affect storage lesion development in individual donors. This study was conducted to evaluate whether variation in hemolysis, microparticle accumulation, phosphatidylserine (PS) exposure, and other storage lesion-associated variables might be a function of the prestorage hematologic and biologic profiles of the donor. STUDY DESIGN AND METHODS: Ten eligible, regular blood donors were paired and studied before donation (fresh blood) and during storage of RBCs in standard blood banking conditions. Plasma and cellular characteristics and modifications were evaluated by standard laboratory and biochemical or biologic analyses as well as by statistical and network analysis tools. RESULTS: Nitrate/nitrite and other bioactive factors exhibited high interdonor variability, which further increased during storage in a donor-specific manner. Storage lesion evaluators, including RBC fragility and PS exposure, fluctuated throughout the storage period in proportion to their values in fresh blood. Donors' levels of phosphatidylserine exposure and hemoglobin F correlated with stored cells' mean cell (RBC) Hb concentration, oxidative stress markers, and cellular fragility. DISCUSSION: Storage lesion indicators change in an orderly fashion, namely, by following donor-related prestorage attributes. These correlations are illustrated for the first time in "prestorage versus storage" biologic networks, which might help determine the best candidates for in vivo biomarkers of storage quality and provide deeper insight into the apparently complex donor variation effect on the RBC storage lesion.

Uric acid variation among regular blood donors is indicative of red blood cell susceptibility to storage lesion markers: A new hypothesis tested.

BACKGROUND: Oxidative stress orchestrates a significant part of the red blood cell (RBC) storage lesion. Considering the tremendous interdonor variability observed in the "storability," namely, the capacity of RBCs to sustain the storage lesion, this study aimed at the elucidation of donor-specific factors that affect the redox homeostasis during the storage of RBCs in standard systems. STUDY DESIGN AND METHODS: The hematologic profile of regular blood donors (n = 78) was evaluated by biochemical analysis of 48 different variables, including in vivo hemolysis and plasma oxidant and antioxidant factors and statistical analysis of the results. The possible effect of the uric acid (UA) variable on RBC storability was investigated in leukoreduced CPD/SAGM RBC units (n = 8) collected from donors exhibiting high or low prestorage levels of UA, throughout the storage period. RESULTS: Among the hematologic variables examined in vivo, cluster analysis grouped the donors according to their serum UA levels. Plasma antioxidant capacity, iron indexes, and protein carbonylation represented covariants of UA factor. RBCs prepared by low- or high-UA donors exhibited significant differences between them in spheroechinocytosis, supernatant antioxidant activity, and other RBC storage lesion-associated variables. CONCLUSION: UA exhibits a storability biomarker potential. Intrinsic variability in plasma UA levels might be related to the interdonor variability observed in the storage capacity of RBCs. A model for the antioxidant effect of UA during the RBC storage is currently proposed.

Glucose 6-phosphate dehydrogenase deficient subjects may be better "storers" than donors of red blood cells.

Storage of packed red blood cells (RBCs) is associated with progressive accumulation of lesions, mostly triggered by energy and oxidative stresses, which potentially compromise the effectiveness of the transfusion therapy. Concerns arise as to whether glucose 6-phosphate dehydrogenase deficient subjects (G6PD(-)), ~5% of the population in the Mediterranean area, should be accepted as routine donors in the light of the increased oxidative stress their RBCs suffer from. To address this question, we first performed morphology (scanning electron microscopy), physiology and omics (proteomics and metabolomics) analyses on stored RBCs from healthy or G6PD(-) donors. We then used an in vitro model of transfusion to simulate transfusion outcomes involving G6PD(-) donors or recipients, by reconstituting G6PD(-) stored or fresh blood with fresh or stored blood from healthy volunteers, respectively, at body temperature. We found that G6PD(-) cells store well in relation to energy, calcium and morphology related parameters, though at the expenses of a compromised anti-oxidant system. Additional stimuli, mimicking post-transfusion conditions (37°C, reconstitution with fresh healthy blood, incubation with oxidants) promoted hemolysis and oxidative lesions in stored G6PD(-) cells in comparison to controls. On the other hand, stored healthy RBC units showed better oxidative parameters and lower removal signaling when reconstituted with G6PD(-) fresh blood compared to control. Although the measured parameters of stored RBCs from the G6PD deficient donors appeared to be acceptable, the results from the in vitro model of transfusion suggest that G6PD(-) RBCs could be more susceptible to hemolysis and oxidative stresses post-transfusion. On the other hand, their chronic exposure to oxidative stress might make them good recipients, as they better tolerate exposure to oxidatively damaged long stored healthy RBCs.

Data on how several physiological parameters of stored red blood cells are similar in glucose 6-phosphate dehydrogenase deficient and sufficient donors.

This article contains data on the variation in several physiological parameters of red blood cells (RBCs) donated by eligible glucose-6-phosphate dehydrogenase (G6PD) deficient donors during storage in standard blood bank conditions compared to control, G6PD sufficient (G6PD(+)) cells. Intracellular reactive oxygen species (ROS) generation, cell fragility and membrane exovesiculation were measured in RBCs throughout the storage period, with or without stimulation by oxidants, supplementation of N-acetylcysteine and energy depletion, following incubation of stored cells for 24 h at 37 °C. Apart from cell characteristics, the total or uric acid-dependent antioxidant capacity of the supernatant in addition to extracellular potassium concentration was determined in RBC units. Finally, procoagulant activity and protein carbonylation levels were measured in the microparticles population. Further information can be found in "Glucose 6-phosphate dehydrogenase deficient subjects may be better "storers" than donors of red blood cells" [1].

Cost-effectiveness of leucoreduction for prevention of febrile non-haemolytic transfusion reactions.

BACKGROUND: The cost-effectiveness of universal leucoreduction of blood components remains unclear. When using leucoreduced red blood cells, the decrease in the rate of febrile non-haemolytic transfusion reactions (FNHTR) is the only proven, meaningful clinical benefit, whose relationship to costs can be calculated relatively easily. The aim of this study was to evaluate the cost-effectiveness of leucoreduction in avoiding FNHTR. MATERIALS AND METHODS: Data were obtained from two large tertiary hospitals in Athens, Greece, over a 4-year period (2009-2012). The incidence of FNHTR in patients transfused with leucoreduced or non-leucodepleted red blood cells, the additional cost of leucoreduction and the cost to treat the FNHTR were estimated. The incremental cost-effectiveness ratio (ICER), which is the ratio of the change in costs to the incremental benefits of leucoreduction, was calculated. RESULTS: In total, 86,032 red blood cell units were transfused. Of these, 53,409 were leucodepleted and 32,623 were non-leucoreduced. Among patients transfused with leucodepleted units, 25 cases (0.047%) met the criteria for having a FNHTR, while in patients treated with non-leucoreduced components, 134 FNHTR were observed (0.411%). The ICER of leucoreduction was € 6,916 (i.e., the cost to prevent one case of FNHTR). CONCLUSIONS: Leucoreduction does not have a favourable cost-effectiveness ratio in relation to the occurrence of FNHTR. However, many factors, which could not be easily and accurately assessed, influence the long-term costs of transfusion. It is imperative to undertake a series of large, meticulously designed clinical studies across the entire spectrum of blood transfusion settings, to investigate most of the parameters involved.