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Background: Critically ill preterm very-low-birthweight (VLBW) neonates (birthweight ≤ 1.5 kg) frequently develop anemia that is treated with red blood cell (RBC) transfusions. Although RBCs transfused to adults demonstrate progressive decreases in posttransfusion 24-hour RBC recovery (PTR 24 ) during storage-to a mean of approximately 85% of the Food and Drug Administration-allowed 42-day storage-limited data in infants indicate no decrease in PTR 24 with storage., Study Design and Methods: We hypothesized that PTR 24 of allogeneic RBCs transfused to anemic VLBW newborns: 1) will be greater than PTR 24 of autologous RBCs transfused into healthy adults and 2) will not decrease with increasing storage duration. RBCs were stored at 4°C for not more than 42 days in AS-3 or AS-5. PTR 24 was determined in 46 VLBW neonates using biotin-labeled RBCs and in 76 healthy adults using 51 Cr-labeled RBCs. Linear mixed-model analysis was used to estimate slopes and intercepts of PTR 24 versus duration of RBC storage., Results: For VLBW newborns, the estimated slope of PTR 24 versus storage did not decrease with the duration of storage (p = 0.18) while for adults it did (p < 0.0001). These estimated slopes differed significantly in adults compared to newborns (p = 0.04). At the allowed 42-day storage limit, projected mean neonatal PTR 24 was 95.9%; for adults, it was 83.8% (p = 0.0002)., Conclusions: These data provide evidence that storage duration of allogeneic RBCs intended for neonates can be increased without affecting PTR 24 . This conclusion supports the practice of transfusing RBCs stored up to 42 days for small-volume neonatal transfusions to limit donor exposure., (© 2017 AABB.)

Background: Measurement of red blood cell (RBC) survival (RCS) is important for investigating pathophysiology and treatment of anemia. Our objective was to validate the multidensity biotin method for RCS determination in sheep, a commonly used model of RBC physiology. [(14) C]Cyanate served as the reference method for long-term RCS because the (51) Cr method (the reference method for humans) is not reliable in sheep., Study Design and Methods: Aliquots of autologous RBCs from eight adult sheep were labeled with [(14) C]cyanate and four separate densities of biotin (BioRBCs) and reinfused. Short-term RCS was assessed by posttransfusion recovery at 24 hours (PTR(24) ); long-term RCS was assessed by the time to 50% survival (T(50) ) and mean potential life span (MPL)., Results: Values for PTR(24) of the four BioRBC densities were not different. Values for RCS as reflected by T(50) and MPL were nearly identical for [(14) C]cyanate and the two intermediate-density BioRBC populations. In contrast, the lowest-density BioRBC population survived slightly longer (p < 0.01), but with a difference of no clinical significance. The highest-density BioRBC population importantly shortened RCS (p < 0.01 compared to the two intermediate densities)., Conclusion: This study provides evidence that BioRBCs labeled at four biotin densities can be used to independently and simultaneously measure short-term RCS and that BioRBCs labeled at the three lowest biotin densities can be used to accurately and simultaneously measure long-term RCS. Because the sheep RBC model is comparable to humans, this nonradioactive method has promise for use in RBC kinetic studies in neonates and pregnant women., (© 2012 American Association of Blood Banks.)

Background: Previous studies have found that nonsteroidal anti-inflammatory drugs (NSAIDs) and statins may impact erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) levels in patients. The current study was performed to determine if NSAID or statin use is associated with lower ESR and CRP in patients with biopsy-proven giant cell arteritis (GCA)., Methods: A retrospective cross-sectional study was conducted that included 161 patients via chart review. Charts of patients with GCA seen at the University of Iowa Hospitals and Clinics from 1960 to 2008 were reviewed. Inclusion criteria were adequate medication records, serum ESR and/or CRP on record, no prior corticosteroid use, and biopsy-positive GCA. Exclusion criteria were the presence of diseases known to elevate ESR or CRP. Main outcome measures included ESR and CRP values measured while evaluating patients for GCA but prior to receiving treatment., Results: Statin nonusers had an ESR of 85.0 mm per hour (interquartile range [IQR] = 60-110 mm per hour) and a CRP of 8.7 mg/dL (IQR = 2.7-16.2 mg/dL). Statin users had an ESR of 57.5 mm per hour (IQR = 35-85) and a CRP of 2.4 mg/dL (IQR = 0.8-15.9 mg/dL). Statin use was associated with a lower ESR (P = 0.005), while there was no significant association with a lower CRP (P = 0.127). NSAID nonusers had an ESR of 98.0 mm per hour (IQR = 64-116) and a CRP of 8.7 mg/dL (IQR = 2.1-16.2 mg/dL). NSAID users had an ESR of 75.0 mm per hour (IQR = 46-98.5 mm per hour) and CRP of 8.0 mg/dL (IQR. = 1.5-16.2 mg/dL). NSAID use was associated with a lower ESR (P = 0.004), but there was no significant association with a lower CRP (P = 0.522)., Conclusion: Statin use and NSAID use were associated with a lower ESR; however, they were not associated with lower CRP values. Clinicians should be aware that statin or NSAID use is associated with lower ESR in patients with GCA, and this test may therefore have lower sensitivity and specificity for recognizing patients with GCA, and CRP may be a superior test to evaluate patients for GCA.

Background: Anemia is a serious problem in critically ill neonates. To investigate the pathophysiology of anemia and responses to red blood cell (RBC) transfusions and erythropoietin therapy, repeated measurement of red blood cell volume (RCV) and blood volume is useful. To extend our previous sheep study in which RBCs were labeled at four different biotin densities, we assessed the validity of this multidensity method for in vivo measurement of circulating RCV in humans., Study Design and Methods: In eight healthy adults, autologous RBCs were biotinylated at each of four biotin densities (6, 18, 54, and 162 µg biotinylation reagent/mL RBC), mixed, and infused intravenously; blood was sampled at 10, 20, and 60 minutes. At each time, RCV was calculated from dilution of individual RBC populations enumerated by flow cytometry. RCV measurements from the population of RBCs biotinylated at 6 µg/mL were chosen as the reference values because this density had been previously validated against the 51Cr method in vitro and in vivo in humans., Results: Values for RCVs were not significantly different among the four densities of biotinylated RBCs at any of the three time points and did not change over 60 minutes., Conclusions: These studies provide evidence that four densities of biotinylated RBCs can be used in vivo for simultaneous, independent, accurate measurements of RCV in humans. We speculate that this method will also be useful for repeated measurement of RCV and blood volume in infants and other patient populations in whom radioactive labels should be avoided., (© 2010 American Association of Blood Banks.)

Background: To investigate the pathophysiology of anemia and responses to red blood cell (RBC) transfusions and erythropoietin, repeated measurement of the circulating red blood cell volume (RCV) would be useful. Ovine erythropoiesis is similar to human erythropoiesis. Accordingly, a method for measuring RCV using either human or sheep RBCs labeled at different biotin densities has been previously validated in vitro. Here preclinical studies validating this method for in vivo measurement of circulating RCV in sheep are reported., Study Design and Methods: For each sheep, autologous RBCs were biotinylated were at four discrete densities (12, 24, 48, and 96µg biotinylation reagent/mL RBCs). The densities were mixed and infused intravenously. Blood was sampled five times over 1 hour beginning at 4 minutes. RCV values were determined based on dilution of each population of biotinylated RBCs and by the [(14) C]cyanate method., Results: There was no difference among RCVs measured at all densities through 16 minutes; however, by 60 minutes, RBCs biotinylated at the highest density overestimated RCV by 7.6%. RCV values increased 41% over the hour, consistent with equilibration with a pool of RBCs sequestered in the spleen. RCV by the [(14) C]cyanate method paralleled results by the biotin method but averaged 8% greater., Conclusions: These studies provide evidence that all four densities of biotinylated RBCs can be used in sheep to simultaneously and independently determine RCV. We speculate that the multidensity biotinylation method will be useful both for multiple simultaneous measurements and for repeated measurement of circulating RCV and blood volume in humans., (© 2010 American Association of Blood Banks.)

Objective: To examine the utility of red blood cell (RBC) zinc protoporphyrin/heme ratio (ZnPP/H) as an indicator of fetal iron status, because unfavorable neurodevelopmental outcomes have been associated with poor iron status at birth, as indicated by low serum ferritin, and because few reliable indicators of fetal and early neonatal iron status exist., Methods: Consecutively studied preterm and term fetuses at delivery included the following groups: (1) control nonhypoxic, (2) fetuses with intrauterine growth retardation (IUGR), and (3) fetuses of insulin-treated mothers (FDM). We hypothesized (1) that rapid growth velocity associated with an accelerated erythropoiesis among normal fetuses will lead to reduced iron delivery to a rapidly expanding RBC mass and higher umbilical cord blood RBC ZnPP/H and (2) that fetuses that are exposed to pathologic hypoxemia will experience an additional increase in erythropoiesis and higher cord ZnPP/H. ZnPP/H was determined on saline-washed cord blood erythrocytes by hematofluorometry and was examined for its relationship with clinical factors and cord blood laboratory measurements indicative of tissue oxygenation (plasma erythropoietin [EPO] and reticulocyte count) and iron status (plasma ferritin and erythrocyte indices). Statistical testing included 1-way analysis of variance, 2-way analysis of variance with covariates, simple linear regression, and multiple regression analysis., Results: Among control group subjects, gestational age at birth was inversely correlated with RBC ZnPP/H and reticulocyte count and positively correlated with ferritin and EPO. Relative to control subjects, IUGR and FDM fetuses at specified gestational age groupings had higher ZnPP/H, lower plasma ferritin, and higher plasma EPO. Statistical modeling of the relationship between ZnPP/H and plasma ferritin among all study groups demonstrated significant impacts of gestational age, plasma EPO, maternal hypertension, and maternal smoking., Conclusions: The inverse association of fetal ZnPP/H with gestational age at birth among control subjects is attributable to erythropoietic stimulation likely as a result of increasing growth velocity at the earliest gestational ages. The relatively higher ZnPP/H observed among fetuses in the IUGR and FDM groups likely is attributable to increased erythropoietic activity secondary to pathologic hypoxemia. Decreased placental iron transfer may also have limited iron availability and contributed to elevated ZnPP/H in the IUGR group. These data support the concept that increased erythropoietic activity and/or limited iron transport may place infants of diabetic mothers and infants with growth retardation at risk for developing systemic iron deficiency later in infancy and in early childhood.

Objective. Although many centers have introduced more restrictive transfusion policies for preterm infants in recent years, the benefits and adverse consequences of allowing lower hematocrit levels have not been systematically evaluated. The objective of this study was to determine if restrictive guidelines for red blood cell (RBC) transfusions for preterm infants can reduce the number of transfusions without adverse consequences. Design, Setting, and Patients. We enrolled 100 hospitalized preterm infants with birth weights of 500 to 1300 g into a randomized clinical trial comparing 2 levels of hematocrit threshold for RBC transfusion. Intervention. The infants were assigned randomly to either the liberal- or the restrictive-transfusion group. For each group, transfusions were given only when the hematocrit level fell below the assigned value. In each group, the transfusion threshold levels decreased with improving clinical status. Main Outcome Measures. We recorded the number of transfusions, the number of donor exposures, and various clinical and physiologic outcomes. Results. Infants in the liberal-transfusion group received more RBC transfusions (5.2 [+ or -] 4.5 [mean [+ or -] SD] vs 3.3 [+ or -] 2.9 in the restrictive-transfusion group). However, the number of donors to whom the infants were exposed was not significantly different (2.8 [+ or -] 2.5 vs 2.2 [+ or -] 2.0). There was no difference between the groups in the percentage of infants who avoided transfusions altogether (12% in the liberal-transfusion group versus 10% in the restrictive-transfusion group). Infants in the restrictive-transfusion group were more likely to have intraparenchymal brain hemorrhage or periventricular leukomalacia, and they had more frequent episodes of apnea, including both mild and severe episodes. Conclusions. Although both transfusion programs were well tolerated, our finding of more frequent major adverse neurologic events in the restrictive RBC-transfusion group suggests that the practice of restrictive transfusions may be harmful to preterm infants. Pediatrics 2005;115:1685-1691; anemia, brain, erythrocyte, preterm infants, transfusions. ABBREVIATION. RBC, red blood cell., Preterm infants are among the most heavily transfused patient populations. In 1991, it was estimated that infants with a birth weight of In recent years, efforts to reduce the number [...]

Background: Two units of red blood cells (RBCs) were typically transfused with each transfusion among hematopoietic stem cell transplant (HSCT) patients. Concerns regarding this practice are increased morbidity, mortality, hospital-acquired infections, length of stay (LOS), and transfusion-related complications. This study compared outcomes of transfusing 1 unit of RBCs per transfusion episode to 2 units of RBCs per episode among HSCT patients.Study Design and Methods: A retrospective record review was used to evaluate a practice change of transfusing 1 RBC unit per episode among autologous and allogeneic HSCT patients. Primary endpoints included: 1) mean number of RBC transfusion episodes during the hospital stay, 2) mean number of RBC units transfused adjusted by LOS, and 3) mean LOS.Results: Among autologous patients, the ratio of mean rate of transfusion episodes for transfusing 1 unit versus 2 units per transfusion was 1.24, with a one-tailed 95% upper limit of 1.42. With a noninferiority upper bound of 1.50, using 1 unit per transfusion episode was noninferior to 2 units per transfusion episode (p = 0.011). Among allogeneic HSCT patients, the ratio of mean transfusion episode rate was 1.26 with a one-tailed 95% upper limit of 1.52, which was slightly above the 1.50 noninferiority bound (p = 0.061).Conclusion: A single-unit transfusion policy was not inferior to the 2-unit policy for autologous HSCT patients and trended toward noninferiority for allogeneic transplant patients. The mean volume of blood per LOS was lower for the 1-unit practice for both groups. The gains from the practice change may outweigh the risks of not changing. [ABSTRACT FROM AUTHOR]

BACKGROUND: Measurement of red blood cell (RBC) survival (RCS) is important for investigating pathophysiology and treatment of anemia. Our objective was to validate the multidensity biotin method for RCS determination in sheep, a commonly used model of RBC physiology. [14C]Cyanate served as the reference method for long-term RCS because the 51Cr method (the reference method for humans) is not reliable in sheep. STUDY DESIGN AND METHODS: Aliquots of autologous RBCs from eight adult sheep were labeled with [14C]cyanate and four separate densities of biotin (BioRBCs) and reinfused. Short-term RCS was assessed by posttransfusion recovery at 24 hours (PTR24); long-term RCS was assessed by the time to 50% survival (T50) and mean potential life span (MPL). RESULTS: Values for PTR24 of the four BioRBC densities were not different. Values for RCS as reflected by T50 and MPL were nearly identical for [14C]cyanate and the two intermediate-density BioRBC populations. In contrast, the lowest-density BioRBC population survived slightly longer (p < 0.01), but with a difference of no clinical significance. The highest-density BioRBC population importantly shortened RCS (p < 0.01 compared to the two intermediate densities). CONCLUSION: This study provides evidence that BioRBCs labeled at four biotin densities can be used to independently and simultaneously measure short-term RCS and that BioRBCs labeled at the three lowest biotin densities can be used to accurately and simultaneously measure long-term RCS. Because the sheep RBC model is comparable to humans, this nonradioactive method has promise for use in RBC kinetic studies in neonates and pregnant women. [ABSTRACT FROM AUTHOR]