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BACKGROUND: In hematologic and transfusion medicine research, measurement of red blood cell (RBC) in vivo kinetics must be safe and accurate. Recent reports indicate use of biotin-labeled RBC (BioRBC) to determine red cell survival (RCS) offers substantial advantages over (51)Cr and other labeling methods. Occasional induction of BioRBC antibodies has been reported. STUDY DESIGN AND METHODS: To investigate the causes and consequences of BioRBC immunization, we reexposed three previously immunized adults to BioRBC and evaluated the safety, antibody emergence, and RCS of BioRBC. RESULTS: BioRBC re-exposure caused an anamnestic increase of plasma BioRBC antibodies at 5–7 days; all were subclass IgG(1) and neutralized by biotinylated albumin, thus indicating structural specificity for the biotin epitope. Concurrently, specific antibody binding to BioRBC was observed in each subject. As biotin label density increased, the proportion of BioRBC that bound increased antibody also increased; the latter was associated with proportional accelerated removal of BioRBC labeled at density 6 μg/mL. In contrast, only one of three subjects exhibited accelerated removal of BioRBC density 2 μg/mL. No adverse clinical or laboratory events were observed. Among three control subjects who did not develop BioRBC antibodies following initial BioRBC exposure, re-exposure induced neither antibody emergence nor accelerated BioRBC removal. DISCUSSION: We conclude re-exposure of immunized subjects to BioRBC can induce anamnestic antibody response that can cause an underestimation of RCS. To minimize chances of antibody induction and underestimation of RCS, we recommend an initial BioRBC exposure volume of ≤10 mL and label densities of ≤18 μg/mL.

Author(s): Gottschall, Jerome; Wu, YanYun; Triulzi, Darrell; Kleinman, Steven; Strauss, Ronald; Zimrin, Ann Butler; McClure, Christopher; Tan, Sylvia; Bialkowski, Walter; Murphy, Edward; Ness, Paul; NHLBI Recipient Epidemiology and Donor Evaluation (REDS-III) Study | Abstract: BackgroundUsing the Recipient and Donor Epidemiology Study-III (REDS-III) recipient and donor databases, we performed a retrospective analysis of platelet use in 12 US hospitals that were participants in REDS-III.Study design and methodsData were electronically extracted from participating transfusion service and blood center computer systems and from medical records of the 12 REDS-III hospitals. All platelet transfusions from 2013 to 2016 given to patients aged 18 years and older were included in the analysis.ResultsThere were 28,843 inpatients and 2987 outpatients who were transfused with 163,719 platelet products (103,371 apheresis, 60,348 whole blood derived); 93.5% of platelets were leukoreduced and 72.5% were irradiated. Forty-six percent were transfused to patients with an International Classification of Diseases, 9th/10th Revision (ICD-9/10) diagnosis of leukemia, myelodysplastic syndrome (MDS), or lymphoma. The general ward and the intensive care unit (ICU) were the most common issue locations. Only 54% of platelet transfusions were ABO identical; and 60.6% of platelet transfusions given to Rh-negative patients were Rh positive. The most common pretransfusion platelet count range for inpatients was 20,000 to 50,000/μL, for outpatients it was 10,000 to 20,000/μL. Among ICU patients, 35% of platelet transfusion episodes had a platelet count of greater than 50,000/μL; this was only 8% for general ward and 2% for outpatients. The median posttransfusion increment, not corrected for platelet dose and/or patient size, ranged from 12,000 to 20,000/μL for inpatients, and from 17,000 to 27,000/μL for outpatients.ConclusionsThese data from one of the largest reviews of platelet transfusion practice to date provide guidance for where to focus future clinical research studies and platelet blood management programs.

The current reference method in the United States for measuring in vivo population red blood cell (RBC) kinetics utilizes chromium-51 (51 Cr) RBC labeling for determining RBC volume, 24-hour posttransfusion RBC recovery, and long-term RBC survival. Here we provide evidence supporting adoption of a method for kinetics that uses the biotin-labeled RBCs (BioRBCs) as a superior, versatile method for both regulatory and investigational purposes. RBC kinetic analysis using BioRBCs has important methodologic, analytical, and safety advantages over 51 Cr-labeled RBCs. We critically review recent advances in labeling human RBCs at multiple and progressively lower biotin label densities for concurrent, accurate, and sensitive determination of both autologous and allogeneic RBC population kinetics. BioRBC methods valid for RBC kinetic studies, including successful variations used by the authors, are presented along with pharmacokinetic modeling approaches for the accurate determination of RBC pharmacokinetic variables in health and disease. The advantages and limitations of the BioRBC method-including its capability of determining multiple BioRBC densities simultaneously in the same individual throughout the entire RBC life span-are presented and compared with the 51 Cr method. Finally, potential applications and limitations of kinetic BioRBC determinations are discussed.

Background Although the subject of many previous studies, the importance of white blood cell (WBC) alloimmunization in granulocyte transfusion therapy has not been settled. In this study, we report the results of the effects of WBC antibodies in the RING (Resolving Infection in Neutropenia with Granulocytes) study, a randomized controlled trial comparing the efficacy of daily granulocyte transfusion therapy plus antimicrobials versus antimicrobials alone; the primary outcome results have been published previously. Study design and methods One hundred fourteen subjects were enrolled in the study. Serum samples for WBC antibody determination were obtained from each subject at baseline and at 2 and 6 weeks. One hundred subjects had at least one antibody test result. Samples were tested for human leukocyte antigen (HLA) Class I and Class II antibodies as well as for granulocyte-specific antibodies using granulocyte agglutination and immunofluorescence techniques. All testing was performed at a central laboratory. Results Baseline WBC alloimmunization was modest, depending somewhat on the assay. Seroconversion during the study was slightly higher in the granulocyte transfusion arm, but the differences were not statistically significant. There was no demonstrable effect of the presence of alloimmunization on the primary outcome (survival and microbial response at 42 days), the occurrence of transfusion reactions (either overall or pulmonary), or posttransfusion neutrophil increments. Conclusion The presence or development of WBC antibodies had no demonstrable effect on any clinical aspect of granulocyte transfusion therapy. It appears that, at least in the patient population studied, there is no evidence suggesting need for concern about recipient WBC alloimmunization when prescribing granulocyte transfusions.

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 (PTR24 ) 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 PTR24 with storage. STUDY DESIGN AND METHODS We hypothesized that PTR24 of allogeneic RBCs transfused to anemic VLBW newborns: 1) will be greater than PTR24 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. PTR24 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 PTR24 versus duration of RBC storage. RESULTS For VLBW newborns, the estimated slope of PTR24 versus storage did not decrease with the duration of storage (p = 0.18) while for adults it did (p

Background Biotin-labeled red blood cells (BioRBCs) are used for in vivo kinetic studies. Because BioRBC dosing occasionally induces antibodies, a sensitive and specific anti-BioRBC detection assay is needed. Study design and methods Aims were to 1) develop a gel card assay to evaluate existing, naturally occurring and BioRBC-induced plasma antibodies, 2) compare gel card and tube agglutination detection results, and 3) test for a relationship of antibody induction and BioRBC dose. Reagent BioRBCs were prepared using sulfo-NHS biotin ranging from densities 18 (BioRBC-18) to 1458 (BioRBC-1458) µg/mL RBCs. Results Among BioRBC-exposed subjects, gel card and tube agglutination results were concordant in 21 of 22 adults and all 19 infant plasma samples. Gel card antibody detection sensitivity was more than 10-fold greater than tube agglutination. Twelve to 16 weeks after BioRBC exposure, induced anti-antibodies were detected by gel card in three of 26 adults (12%) at reagent densities BioRBC-256 or less, but in none of 41 infants. Importantly, induced anti-BioRBC antibodies were associated with higher BioRBC dose (p = 0.008); no antibodies were detected in 18 subjects who received BioRBC doses less than or equal to BioRBC-18. For noninduced BioRBC antibodies, six of 1125 naive adults (0.3%) and none of 46 naive infants demonstrated existing anti-BioRBC antibodies using reagent BioRBC-140 or -162. Existing anti-BioRBCs were all neutralized by biotin compounds, while induced antibodies were not. Conclusions The gel card assay is more sensitive than the tube agglutination assay. We recommend reagent BioRBC-256 for identifying anti-BioRBCs. Use of a low total RBC biotin label dose (≤ BioRBC-18) may minimize antibody induction.

BACKGROUND Prevalence estimates of the serious hazards of transfusion vary widely. We hypothesized that the current reporting infrastructure in the United States fails to capture many transfusion reactions and undertook a multicenter study using active surveillance, data review, and adjudication to test this hypothesis. STUDY DESIGN AND METHODS A retrospective record review was completed for a random sample of 17% of all inpatient transfusion episodes over 6 months at four academic tertiary care hospitals, with an episode defined as all blood products released to a patient in 6 hours. Data were recorded by trained clinical research nurses, and serious reactions were adjudicated by a panel of transfusion medicine experts. RESULTS Of 4857 transfusion episodes investigated, 1.1% were associated with a serious reaction. Transfusion-associated circulatory overload was the most frequent serious reaction noted, being identified in 1% of transfusion episodes. Despite clinical notes describing a potential transfusion association in 59% of these cases, only 5.1% were reported to the transfusion service. Suspected transfusion-related acute lung injury/possible transfusion-related acute lung injury, anaphylactic, and hypotensive reactions were noted in 0.08, 0.02, and 0.02% of transfusion episodes, respectively. Minor reactions, including febrile nonhemolytic and allergic, were noted in 0.62 and 0.29% of transfusion episodes, respectively, with 30 and 50% reported to the transfusion service. CONCLUSION Underreporting of cardiopulmonary transfusion reactions is striking among academic, tertiary care hospitals. Complete and accurate reporting is essential to identify, define, establish pathogenesis, and mitigate/treat transfusion reactions. A better understanding of the failure to report may improve the accuracy of passive reporting systems.

Although the subject of many previous studies, the importance of white blood cell (WBC) alloimmunization in granulocyte transfusion therapy has not been settled. In this study, we report the results of the effects of WBC antibodies in the RING (Resolving Infection in Neutropenia with Granulocytes) study, a randomized controlled trial comparing the efficacy of daily granulocyte transfusion therapy plus antimicrobials versus antimicrobials alone; the primary outcome results have been published previously.One hundred fourteen subjects were enrolled in the study. Serum samples for WBC antibody determination were obtained from each subject at baseline and at 2 and 6 weeks. One hundred subjects had at least one antibody test result. Samples were tested for human leukocyte antigen (HLA) Class I and Class II antibodies as well as for granulocyte-specific antibodies using granulocyte agglutination and immunofluorescence techniques. All testing was performed at a central laboratory.Baseline WBC alloimmunization was modest, depending somewhat on the assay. Seroconversion during the study was slightly higher in the granulocyte transfusion arm, but the differences were not statistically significant. There was no demonstrable effect of the presence of alloimmunization on the primary outcome (survival and microbial response at 42 days), the occurrence of transfusion reactions (either overall or pulmonary), or posttransfusion neutrophil increments.The presence or development of WBC antibodies had no demonstrable effect on any clinical aspect of granulocyte transfusion therapy. It appears that, at least in the patient population studied, there is no evidence suggesting need for concern about recipient WBC alloimmunization when prescribing granulocyte transfusions.

BACKGROUND How platelet (PLT) product characteristics such as dose, source (whole blood-derived (WBD) vs. apheresis), storage duration, and ABO matching status affect the risks of transfusion-related adverse events (TRAEs) is unclear. Similarly, more information is needed to define how recipient characteristics affect the frequency of TRAEs following PLT transfusion.

Biotin-labeled red blood cells (BioRBCs) are used for in vivo kinetic studies. Because BioRBC dosing occasionally induces antibodies, a sensitive and specific anti-BioRBC detection assay is needed.Aims were to 1) develop a gel card assay to evaluate existing, naturally occurring and BioRBC-induced plasma antibodies, 2) compare gel card and tube agglutination detection results, and 3) test for a relationship of antibody induction and BioRBC dose. Reagent BioRBCs were prepared using sulfo-NHS biotin ranging from densities 18 (BioRBC-18) to 1458 (BioRBC-1458) µg/mL RBCs.Among BioRBC-exposed subjects, gel card and tube agglutination results were concordant in 21 of 22 adults and all 19 infant plasma samples. Gel card antibody detection sensitivity was more than 10-fold greater than tube agglutination. Twelve to 16 weeks after BioRBC exposure, induced anti-antibodies were detected by gel card in three of 26 adults (12%) at reagent densities BioRBC-256 or less, but in none of 41 infants. Importantly, induced anti-BioRBC antibodies were associated with higher BioRBC dose (p = 0.008); no antibodies were detected in 18 subjects who received BioRBC doses less than or equal to BioRBC-18. For noninduced BioRBC antibodies, six of 1125 naïve adults (0.3%) and none of 46 naïve infants demonstrated existing anti-BioRBC antibodies using reagent BioRBC-140 or -162. Existing anti-BioRBCs were all neutralized by biotin compounds, while induced antibodies were not.The gel card assay is more sensitive than the tube agglutination assay. We recommend reagent BioRBC-256 for identifying anti-BioRBCs. Use of a low total RBC biotin label dose (≤ BioRBC-18) may minimize antibody induction.

Background Prevention of red blood cell (RBC) alloimmunization in patients with sickle cell disease (SCD) focuses on phenotypic RBC matching. We assessed alloimmunization among transfused patients with SCD after implementing leukoreduction and prophylactic antigen matching (PAM). Study design and methods Retrospective review of transfusion and medical records for SCD patients 18 months to 81 years of age was performed covering two 5-year periods: Period 1, no PAM, occasional leukoreduction, and Period 2, consistent leukoreduction and extended PAM (Rh, Kell, S, Fy, Jk) for patients already alloimmunized. Patients transfused in Period 1 were excluded from Period 2. Results A total of 293 patients were transfused in Period 1 and 183 in Period 2. Median time between first sample and last type and screen after transfusion was 2.12 years in Period 1 and 1.03 years in Period 2. Initial alloimmunization prevalence was lower in Period 2 (26.2%) versus Period 1 (37.5%) and after subsequent transfusions in Period 2 (23.8%) versus Period 1 (45.7%), although without significant difference after adjusting for number of units transfused, percentage of leukoreduced RBCs, sex, and age. Alloimmunized patients received more nonleukoreduced RBCs in Period 1 than nonalloimmunized. Patients transfused during inflammatory conditions were not significantly more likely to become alloimmunized. Conclusions The prevalence of initial and subsequent RBC alloimmunization in Period 2 was lower than that in Period 1; however, overall prevalence remained high. We recommend leukoreduced, hemoglobin S-negative Rh and Kell PAM RBCs for transfusion of patients with SCD. Component and recipient factors affecting alloimmunization should be studied further.

Characterization of the behavior of red blood cells (RBCs) in the bloodstream after transfusion (i.e., posttransfusion RBC kinetics) generally consists of measurement of RBC volume (RCV) and RBC survival (RCS) assessed by posttransfusion recovery at 24 hours (PTR24) and at later times, that is, to 50% survival (T50) and to the mean potential life span (MPL). Posttransfusion RBC kinetic studies provide information valuable in establishing the diagnosis and defining the pathogenesis of hematologic conditions and in determining optimal RBC transfusion and blood banking practices.1 Ideally, techniques for measuring posttransfusion RBC kinetics should be precise, safe, and easily applied. They should also be broadly applicable to diverse study populations and require minimal blood volumes for sampling, labeling, and analysis—particularly for infants. Methods utilizing chromium-51 (51Cr) radionuclide RBC labeling have been adopted by the International Committee for Standardization in Hematology as the reference method for determining posttransfusion RCS in humans.2 Unfortunately, because some species experience excessive rates of loss of 51Cr from RBCs (3%–4% per day in sheep, horses, cattle, goats, cats, and rats, compared to approx. 1% in humans),3 the 51Cr labeling method is not reliable for all mammalian species. Moreover, the costs for radiation containment and disposal are substantial and increasing. Recently, a method based on biotin-labeled RBCs (BioRBC) that does not require radiation exposure has been developed and validated for use in posttransfusion kinetic studies in a broad spectrum of mammalian species. In addition to overcoming the aforementioned limitations of the 51Cr method, the BioRBC method achieves similar sensitivity while requiring analytic blood volumes as small as 3 μL4,5 compared to the 1 to 2 mL recommended for the 51Cr method.3 The focus of this study was on validating the BioRBC labeling method in sheep. This is important because ovine fetal and newborn cardiovascular, pulmonary, and of relevance for this report, hematologic development and physiology resemble those of humans.6 In particular, ovine erythropoiesis in the fetus, neonate, and adult is similar to the human, and regulation of erythropoiesis and RBC kinetics in the ovine model are currently active areas of study.7–10 Accordingly, lambs and sheep are logical animal models for preclinical testing of this method for measuring RCV and RCS. We recently demonstrated that autologous sheep RBCs labeled at four discrete, low biotin densities yielded RCV results that are equivalent to one another and are within 10% of values determined simultaneously using [14C]cyanate-labeled RBCs.11 Further, we have applied the multidensity method to measurement of RCV in human adults with similar success. We were able to extend these human studies to survival of the BioRBCs and determine short-term and long-term RCS in eight participants. However, use of a radioactive-labeled marker such as 51Cr was not included because of the technical and financial demands. In this study, we extend these preclinical animal studies to assess the validity of RCS determined in the same animals using RBCs labeled with the same four biotin densities and with [14C]cyanate. Because of the additional complexities of dealing with an animal with a large spleen that sequesters up to 30% of RBCs, of the difficulties of measuring radiolabeled RBCs, and the need to fit a mathematical curve to accurately determine the proportion of each of the BioRBC peaks, we have only recently completed this analysis for the current report. To do so, we assessed short-term RCS by PTR24 and long-term RCS by T50 and by MPL. For long-term RCS, we hypothesized that these two variables would agree closely when determined using RBCs labeled with the lower BioRBC densities and that they would agree with RCS determined using [14C]cyanate.12

Red blood cells (RBCs) can be removed from the bloodstream at an accelerated rate by antibody-mediated mechanisms in a number of immunologic conditions including the following: 1) autoimmune hemolytic anemias, 2) transfusion of incompatible allogeneic RBCs into a recipient whose blood contains a corresponding alloantibody, 3) transfusion of passive antibodies into a recipient whose RBCs express the cognate antigen, 4) transplacental transfer of maternal allogeneic RBC antibodies into a fetus with RBCs expressing the cognate antigen resulting in alloimmune hemolytic disease of the fetus and newborn, and 5) posttransplantation transfer of viable donor lymphocytes capable of producing antibodies directed against recipient RBCs (e.g., group O donor into group A recipient). When caring for patients with these disorders, having an accurate and safe method for determining in vivo RBC kinetics would be of considerable value for establishing the diagnosis, defining the pathophysiology, and assessing the response to therapy. The availability of RBC survival (RCS) methods that address safety issues (e.g., avoidance of radioactivity) is particularly important for vulnerable patient populations including fetuses, neonates, children, and pregnant women. Direct assessment of RCS requires the ability to distinguish cohort-labeled RBCs from the remaining RBCs in the circulation and to express their number as the relative proportion of labeled RBCs to total RBCs in that blood sample. The internationally recognized reference method for measuring RCS uses autologous or allogeneic RBCs labeled with chromium 51 (51Cr) and is based on concentration of 51Cr per unit volume of blood.1 Because transfusion of 51Cr-labeled RBCs exposes the recipient to radiation, this approach is viewed as unacceptable for research studies in the human fetus, neonate, and pregnant woman. Our laboratory and others2-4 have developed methods for measuring RCS in humans based on labeling of RBCs with biotin at one5-10 or more11 densities. Here the term density refers to biotin labels per RBC and is determined by our selection of the concentration of biotinylating reagent per milliliter of RBCs in the biotinylation reaction mixture. Biotin-labeled RBCs (BioRBCs) are quickly and easily enumerated by flow cytometry.11 The biotin RBC method has the following safety and technical advantages over the standard 51Cr method: 1) study subjects including vulnerable populations are not exposed to radiation; 2) small blood volumes (e.g., 20 μL) are required for monitoring; and 3) multiple, independent RCS measurements can be made simultaneously in the same individual by labeling RBCs at more than one biotin density. The aim of this study was to determine whether RBCs labeled with biotin at a single density can be used to accurately measure shortened RCS of RBCs experimentally coated (opsonized) with antibody simulating the situation present in immune-mediated hemolytic anemia. We hypothesized that short-term and long-term RCS measured using BioRBCs would agree with RCS determined using RBCs labeled with 51Cr.

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.

BACKGROUND Safe, accurate methods permitting simultaneous and/or repeated measurement of red blood cell (RBC) survival (RCS) are important to investigate pathophysiology and therapy of anemia. Methods using chromium 51 (51Cr) -labeled RBCs are unacceptable for infants, children, and pregnant women. We report RCS measured in vivo using RBCs labeled with several densities of biotin (BioRBCs).

A “benchmark” is a standard or measure by which others can be assessed and/or compared. Benchmarking is the process of gathering information (ie, data and/or expert opinions) to set the benchmark. The greater the care, precision and validation taken during the benchmarking process, the more accurately the benchmark will reflect the optimal practices/issues in question and, in turn, allow the best point of reference for comparing/judging/instructing/advising others. In this issue of Transfusion, Fung et al report results of a benchmarking survey performed by the University HealthSystem Consortium (UHC) to assess the acceptability of various RBC anticoagulant/storage solutions and to determine the existence, or lack thereof, of policies to avoid possible hyperkalemia during RBC transfusions given to infants at member institutions.(1) The authors state in the title that this is a “benchmarking study” — which by convention implies that the results will serve as a standard by which others may be measured and/or as a point of reference from which other measurements can be made. Although the need to establish benchmarks for the issues raised (ie, RBC anticoagulant/storage solutions for infant transfusions and policies to avoid potential problems with transfusion-induced hyperkalemia) are well stated in the introduction by Fung et al,(1) the limitations/shortcomings of the benchmarking survey are multiple (as pointed-out by the authors in the discussion section). Thus, the extent to which the findings, conclusions and recommendations of Fung et al should be directly applied to neonatal/infant transfusion practices can be questioned. The basis for my opinion pertaining to limitations/shortcomings, is summarized by the following critical points — many of which were mentioned by the authors themselves,(1) but warrant emphasis here. First, response to the survey by institutions surveyed was only modest (47 of 107 UHC members = 44% for the RBC anticoagulant/preservative section and 45 of 107 = 42% for the hyperkalemia section), with no explanation offered as to why nonresponders failed to reply — other than mentioning that only 77 UHC members are “benchmarking program members” and noting that “no attempt was made at increasing response rate” beyond a few modest efforts.(1) Because UHC members are academic medical centers, one might assume that their practices would be as “evidence-based” as possible. Accordingly, to avoid possible misinformation due to reporting bias, more efforts should have been made to increase response rates to get a complete and accurate picture of member practices — to establish benchmarks that most likely reflect best/optimal practices. Second, one should question whether the most knowledgeable people completed the survey. The respondents were not neonatologists/pediatricians and only 21% were transfusion/pathology physicians. The remaining 79% of respondents were supervisors/managers/administrators.(1) Although these non-physician respondents can review blood bank/laboratory policies/procedures to answer survey questions, it is likely that they will not have in depth knowledge of transfusion practice guidelines/policies of the Departments of Pediatrics and Neonatology Divisions or of the Departments of Nursing. Moreover, they likely will not be familiar with the preferences/practices of physicians prescribing RBC transfusions for infants — particularly pertaining to potassium concerns. Third, to extend the second point, collecting data for which RBC anticoagulant/preservative solutions are “acceptable” provides only limited benchmarking data. For purposes of planning educational programs and recommending evidence-based guidelines/practices, it would be much more informative to know which anticoagulant/preservative solutions are “preferred” and, in the many institutions accepting multiple solutions, what percentage of RBC transfusions are actually given with the “accepted” anticoagulant/preservative solutions. In 19 of 47 responding institutions, four or five different anticoagulant/preservative solutions were “acceptable” with no indication as to which one(s) the prescribing physicians preferred and/or to what extent RBCs stored in different solutions were transfused. Simply acknowledging a solution is “acceptable” does not mean it is preferred or even actually used at an institution. Fourth, no mention is made as to how, or even whether, the survey answers were validated for completeness or accuracy. The authors stated that although no formal validation was performed, all participating UHC members were given opportunities to review and make corrections after close of the survey.(1) It would have increased credibility to report the number/percentage of UHC members who actually did review the completed survey and made corrections — and, in particular, to document whether answers to the survey were ever reviewed by physicians and nurses actually involved in RBC transfusions given to infants. Regarding the acceptability of anticoagulant/preservative solutions, the authors state that the decision to transfuse RBCs stored in additive solutions (AS-1, AS-3, AS-5) should be made by the medical director of the transfusion service, in consultation with institutional neonatologists — a point with which all would agree. The authors then make a rather feeble case for recommending RBCs stored in additive solutions as the best practice for low volume (

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 96 µg 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 [14C]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 [14C]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.

BACKGROUND: Many clinical practices in transfusion medicine are controversial and/or lack definitive guidelines established by sound clinical trials. Although recommendations based on results of clinical trials performed using infants and children may not always be applied directly to adults—and vice versa—lessons learned from pediatric trials can be useful when critically assessing the design/results/conclusions of adult trials. STUDY DESIGN AND METHODS: Four randomized clinical trials (RCTs) studying pediatric patients were critically reviewed. They addressed two red blood cell (RBC) transfusion issues: 1) transfusion guidelines by which RBC transfusions are “triggered” by liberal (LIB; high pretransfusion patient hematocrit [Hct] levels) versus being “triggered” by restricted (RES; low pretransfusion Hct levels) and 2) transfusion of fresh RBCs (≤7 days' storage) versus RBCs (up to 42 days' storage). RESULTS: Findings established by primary outcomes generally were firm (e.g., fewer RBC transfusions were given to infants/children managed by RES guidelines; transfusing small volumes of RBCs stored up to 42 days to preterm infants diminished allogeneic donor exposures and were equally efficacious and safe as fresh RBCs stored ≤7 days). Findings based on secondary outcomes, subset, and post hoc analyses were inconsistent (e.g., clinical outcomes were equivalent after LIB or RES transfusions in only two of three RCTs; in the third, more neurologic problems were found in neonates given RES transfusions). CONCLUSIONS: Clinical practices should be based on data pertaining to the primary outcomes of RCTs, because trials are designed and statistically powered to address these issues. Clinical practices suggested by analysis of secondary outcomes, subsets of patients, and post hoc analyses should be applied cautiously until studied further—ideally, as primary outcomes in subsequent RCTs.

Many aspects of hematopoiesis are either incompletely developed in preterm infants or still functioning to serve the fetus (i.e., the intrauterine counterpart to a liveborn preterm neonate). This delayed development and/or slow adaptation to extrauterine life diminishes the capacity of the neonate to produce red blood cells (RBCs), platelets (PLTs), and neutrophils—particularly during the stress of life-threatening illnesses encountered after preterm birth such as sepsis, severe pulmonary dysfunction, necrotizing enterocolitis, and immune cytopenias. The serious medical and/or surgical problems of preterm birth can be further complicated by phlebotomy blood losses, bleeding, hemolysis, and consumptive coagulopathy. To illustrate, some preterm infants, especially those with birth weight less than 1.0 kg and respiratory distress, are given numerous RBC transfusions early in life owing to several interacting factors. Neonates delivered before 28 weeks of gestation (birth weight

Background A photochemical treatment (PCT) system has been developed to inactivate a broad spectrum of pathogens and white blood cells in platelet (PLT) products. The system comprises PLT additive solution (PAS III), amotosalen HCl, a compound adsorption device (CAD), a microprocessor-controlled ultraviolet A light source, and a commercially assembled system of interconnected plastic containers. Study design and methods A clinical prototype of the PCT system was used in a large, randomized, controlled, double-blind, Phase III clinical trial (SPRINT) that compared the efficacy and safety of PCT apheresis PLTs to untreated apheresis PLTs. The ability of multiple users was assessed in a blood center setting to perform the PCT and meet target process specifications. Results Each parameter was evaluated for 2237 to 2855 PCT PLT products. PCT requirements with respect to mean PLT dose, volume, and plasma content were met. Transfused PCT PLT products contained a mean of 3.6 x 10(11) +/- 0.7 x 10(11) PLTs. The clinical process, which included trial-specific samples, resulted in a mean PLT loss of 0.8 x 10(11) +/- 0.6 x 10(11) PLTs per product. CAD treatment effectively reduced the amotosalen concentration from a mean of 31.9 +/- 5.3 micromol per L after illumination to a mean of 0.41 +/- 0.56 micromol per L after CAD. In general, there was little variation between sites for any parameter. Conclusions The PCT process was successfully implemented by 12 blood centers in the United States to produce PCT PLTs used in a prospective, randomized trial where therapeutic efficacy of PCT PLTs was demonstrated. Process control was achieved under blood bank operating conditions.

BACKGROUND: The SPRINT trial examined efficacy and safety of photochemically treated (PCT) platelets (PLTs). PCT PLTs were equivalent to untreated (control) PLTs for prevention of bleeding. Transfused PLT dose and corrected count increments (CIs), however, were lower and transfusion intervals were shorter for PCT PLTs, resulting in more PCT than control transfusions. PLT dose was analyzed to determine the impact of the number of PLTs transfused on transfusion requirements. STUDY DESIGN AND METHODS: Transfusion response was compared for patients with all doses of ≥3.0 × 1011 and the complementary subset of patients with any dose of fewer than 3.0 × 1011. Analyses included comparison of bleeding, number of PLT and red blood cell (RBC) transfusions, transfusion intervals, and CIs between PCT and control groups within each PLT dose subset. RESULTS: Mean PLT dose per transfusion in the PCT group was lower than in the control group (3.7 × 1011 vs. 4.0 × 1011; p

BACKGROUND: Uncommonly, antibodies that appear to exhibit antigenic specificity on red blood cell (RBC) panels fail to maintain specificity following alloadsorption (i.e., they mimic antigenic specificity). Understanding both the pitfalls and the proper pathways to establish the diagnosis and to interpret the clinical significance of these mimicking antibodies is important for patient management. CASE REPORT: A 68-year-old woman was admitted with dyspnea, anemia, bilateral pulmonary emboli, and metastatic ovarian cancer. Blood bank evaluation identified anti-E reactivity in the patient's plasma sample and a positive direct antiglobulin test (DAT). RESULTS: The DAT was positive for immunoglobulin G and negative for C3b. An eluate of the RBCs showed E-antigen specificity on a RBC antibody panel. Repeat serologic testing with RBC antibody panels with adsorbed patient plasma showed removal of apparent anti-E reactivity with either E-antigen-positive or E-antigen-negative RBC stroma. CONCLUSION: A mimicking autoantibody with apparent E-antigen specificity was identified in the plasma sample of a woman with newly diagnosed ovarian cancer. Despite their relative low frequency, mimicking antibodies, whether auto- or alloantibodies, may interfere with the timely issuance of compatible blood products and may confuse laboratory and clinical staff. Determining the clinical significance of the antibody, by taking into account the RBC phenotype of the patient and the antigen prevalence in the general population, guides the extent of workup required to best utilize resources while assuring patient safety.

Background The feasibility, efficacy, and safety of transfusing stored allogeneic RBCs has been demonstrated for small-volume transfusions given to infants. We measured the posttransfusion recovery and intravascular survival of allogeneic RBCs stored up to 42 days to further elucidate their efficacy.

BACKGROUND: The extend potential applications of a nonradioactive method for measuring circulating RBC volume, we tested the hypothesis that RBC volume could be determined independently using two populations of RBCs labeled with low-density biotin (LDB1) and high-density biotin (HDB). STUDY DESIGN AND METHODS: In 10 healthy adults, autologous RBCs were labeled with HDB, LDB, or 51Cr. The labeled RBCs were mixed and transfused. RBC volume was measured in postinfusion peripheral venous blood by quantitating dilution of each population of labeled RBCs. RESULTS: RBC volume measured using either LDB or HDB cells agreed well with RBC volume measured using 51Cr. For the regression of RBC volume by LDB versus RBC volume by 51Cr, correlation = 0.994 and slope = 0.933. For HDB versus 51Cr, correlation = 0.982 and slope = 0.953. RBC volume measured a second time in four subjects with HDB agreed well; mean CV for the differences between HDB and 51Cr were less than 5 percent. CONCLUSIONS: Using RBCs labeled with two different densities of biotin, RBC volume can be accurately measured simultaneously and repeatedly in the same subject without radiation exposure.

BACKGROUND: One problem assessing the hematologic physiology of preterm infants after delivery and/or the efficacy and toxicity of therapeutic interventions affecting RBC measurements is the inability of blood Hct values to accurately reflect circulating RBC volume—owing to changes in plasma volume that influence Hct (i.e., a fall in plasma volume concentrates RBCs to increase Hct; a rise in plasma volume dilutes RBCs to decrease Hct). STUDY DESIGN AND METHODS: As part of a randomized, clinical trial testing the hypothesis that delayed clamping of the umbilical cord at delivery expands neonatal circulating RBC volume, blood Hct was compared to circulating RBC volume results measured directly with autologous, biotinylated RBCs or estimated mathematically with neonatal body weight and Hct values in neonates after immediate or delayed (60 sec) cord clamping. RESULTS: Circulating RBC volume measured directly with biotinylated RBCs significantly increased (p=0.04) in neonates after delayed (42.1 ± 7.8 mL/kg) versus immediate (36.8 ± 6.3 mL/kg) cord clamping—a difference not detected indirectly by measuring Hct or estimating circulating RBC volume mathematically. CONCLUSIONS: Because true hematologic effects of delayed versus immediate cord clamping may not be apparent or may be misinterpreted, when based on indirect measurements of Hct or calculations of circulating RBC volume, it is important to measure circulating RBC volume directly—as done with autologous, biotinylated RBCs—to document whether delayed cord clamping truly results in a transfer of significant quantities of RBCs from placenta to neonate. The clinical benefits and potential toxicities of increased RBC transfer to neonates require further studies.

We are writing regarding the following comment by Oliver and colleagues1 in the August issue of TRANSFUSION. The authors state in the Introduction that “Radioisotope chromium 51 (51Cr) labeling of blood, despite its disadvantages, is still the only reliable method to predict the intravascular success of an incompatible transfusion. Alternative techniques such as direct biotinylation of red blood cells (RBCs), despite their promise, have not been routinely adopted.” We concur that biotinylated red blood cells (RBCs) have not yet been routinely adopted for quantitation of RBC survival, due in part to the current Food and Drug Administration requirement that an investigational new drug is required for studies that include transfusion with biotin-labeled RBCs. Nonetheless, several factors lead us to predict that measurement of RBC survival using the biotin label will be considered to serve as the reference method eventually. More recent publications than those cited by Oliver and colleagues indicate that the biotin method for labeling RBCs is now reaching its promise. Human RBCs may be reliably biotinylated ex vivo. Ten to 50 mL of labeled RBCs administered to a 70-kg adult yield 0.4% to 2% biotinylated RBCs in the bloodstream; this initial percentage is adequate to permit accurate tracking by flow cytometry for greater than 85% of RBC survival.2,3 In addition to basic measures of RBC recovery and life span, the biotin method has been used in humans for studies to compare survival of multiple RBC populations concurrently in the same individual and to assess age-dependent changes in RBCs, including the following: The survival characteristics of two populations of RBCs that were labeled with different biotin densities and were distinguishable by flow cytometry were simultaneously studied in the same study subject.2 The 51Cr RBC label can be used for only a single population of RBCs at any one time and, consequently, studies of multiple RBC populations must be done sequentially—possibly, introducing biologic and/or temporal variability because studies were not done concurrently. Time-dependent changes in the properties of sickle RBCs have been determined, including the survival of biotinylated RBCs containing HbF versus those without detectable HbF.4 The rate of formation of glycated Hb (e.g., HbA1c) in controls and patients with diabetes determined using magnetic isolation of aging biotin-labeled RBCs has been helpful in interpreting the biologic and clinical significance of glycated Hb as an indicator of high blood glucose levels and long-term complications of diabetes.5 In studies such as those by Mock and colleagues2 and Franco,3 understanding intrasubject variability in RBC survival is important. The accuracy of the 51Cr method is limited due to dissociation from the beta-chain of Hb in the RBCs at rates that vary substantially among individuals and even more among species. This loss of label has a direct effect on accuracy of RBC life span quantitation determined with 51Cr. The situation is different with biotinylated RBCs, even though up to 40% of the covalently linked biotin labels on the outward facing membrane of the RBC are lost during the first few weeks in the circulation. Because the biotinylated RBCs are examined and enumerated individually by flow cytometry and continue to fall within the designated region for a positive cell, they are counted accurately. Accordingly, RBC recovery and life span can be quantitated until nearly all of the biotin-labeled RBCs are removed from the circulation, that is, until the biotin-labeled RBCs fall below 0.06% of the circulating RBCs. The biotin RBC label has been used successfully in all mammals tested thus far and is thus useful in preclinical as well as clinical studies. Current information indicates that biotinylated RBCs may be used safely. In adult humans, the biotin RBC label has been associated with the development of transient agglutinating antibodies to biotin-labeled RBCs in approximately 15% of adult study subjects infused with 50 mL of biotinylated RBCs.6 In the 12 years since the publication of these observations, we have observed only one of eight (13%) additional adult participants who developed a transient positive direct antibody result (Table 1).2 Of note, in this more recent report, subjects were infused with four times the volume of biotinylated RBCs (200 mL) containing an estimated sevenfold greater biotin density per RBC without an increase in the percentage of individuals developing antibodies. The development of antibodies to biotin-labeled RBCs had no effect on the survival of biotin-labeled RBCs. The four adult subjects who developed antibodies to biotinylated RBCs have not developed an identifiable change in the rate of elimination of biotin-labeled RBCs,2,6 clinical signs, or symptoms (personal follow-up communication with study subjects). However, we note that none of these four individuals have been rechallenged with biotinylated RBCs. TABLE 1 Time course after transfusion of antibodies to biotinylated RBCs We write to call these more recent studies utilizing biotin labeling of RBCs to the attention of the authors and other investigators performing RBC kinetic studies so that the advantages of biotin-labeled RBCs can be exploited.

HES solutions provide a sterile, alternative colloidal fluid to albumin solutions and/or plasma in the management of patients who need plasma volume expansion. Solutions of HES are widely accepted internationally but are used only modestly in the United States, largely because of concerns over hemostasis.A randomized, blinded, two-arm trial comparing the hemostatic effects of pentastarch versus hetastarch when infused in the clinically relevant dose of 90 g of HES dissolved in 1.5 L of saline was conducted. Multiple studies of fibrin clot formation, fibrinogen/fibrinolysis, and platelet (PLT) functions were performed before and on multiple occasions for 70 days following HES infusion.Several significant abnormalities of hemostasis assay results occurred following HES infusions, with hetastarch causing significantly greater abnormalities than pentastarch. Individual clotting proteins and blood PLTs fell modestly because of plasma volume expansion and hemodilution. A fall in excess of that caused by hemodilution was demonstrated for von Willebrand factor antigen plus its associated FVIII and ristocetin cofactor activities. The partial thromboplastin time was prolonged, whereas the thrombin time was shortened. Plt function abnormalities were seen in most subjects to a modest degree. Studies of fibrinolysis were normal.Solutions of hetastarch produce significant abnormalities of some hemostasis laboratory results when infused at clinically relevant doses, but it is unlikely that the modest hemostatic abnormalities produced at these doses per se would lead to clinical bleeding. Hetastarch causes greater hemostatic abnormalities than pentastarch, and because both HES solutions have comparable plasma volume-expanding effects, it is reasonable to prefer pentastarch as a plasma volume expander.

BACKGROUND: A relatively young man (43 years old) was found to have a cataract after receiving prednisone before each of 35 neutrophil (PMN) donations over several years. Because corticosteroids are known to induce posterior subcapsular cataracts (PSCs), additional repeat PMN donors were examined ophthalmologically. STUDY DESIGN AND METHODS: A controlled, blinded study was performed in 11 PMN donors who received prednisone with or without G–CSF before 17 to 46 leukapheresis donations over an average of 8.5 years. Control subjects were nine plateletpheresis donors of comparable age and donation experience, but they had never donated PMNs. A complete eye examination was performed by an ophthalmologist who was unaware of the donor's status (PMN vs. platelet). RESULTS: Mild PSCs were found in 36 percent (4/11) of PMN donors versus 0 of 9 platelet donors (p = 0.068). Five of the 22 PMN donor eyes involved versus 0 of the 18 platelet donor eyes involved exhibited PSCs (p = 0.040). Cortical and nuclear cataracts were found similarly in both groups of donors (82% PMN vs. 56% platelet donors; p = 0.217); this indicated that lifestyle factors, independent of corticosteroids, that might predispose to cataract formation probably were comparable. CONCLUSION: Corticosteroids given before PMN donations by leukapheresis might increase the risk of PSCs. Because of widespread renewed interest in PMN transfusions, this potential risk factor—if confirmed by studies of additional PMN donors—is of great international importance. Other centers are urged to perform ophthalmologic examinations on repeat PMN donors to clarify this issue.

BACKGROUND: Preterm infants are among the most heavily transfused of patient groups, yet multiply transfused infants only rarely produce alloantibodies against RBC or WBC antigens. It is not known whether rates of alloimmunization might be increased by repeated exposure to RBCs and WBCs from the same donor, as in limited-donor-exposure programs, or whether infants might benefit from WBC-reduced RBC components as a means of diminishing the risk of possible alloimmunization. STUDY DESIGN AND METHODS: Preterm infants (birth weight 0.6-1.3 kg) received prestorage WBC-reduced RBCs from dedicated donors, collected in AS-3 as a means of limiting donor exposures. Blood samples were collected serially from infants shortly after birth until either discharge or age 6 months and were studied for RBC and WBC antibodies—the latter with reactivity against either HLA class I or neutrophil-specific antigens. RESULTS: Thirty preterm infants received 139 transfusions (mean, 4.6; median, 4 transfusions per infant), with 81 percent of transfusions obtained from one donor per infant. Eighty-four blood samples (mean, 2.7/infant) were studied, and no infant produced RBC antibodies. Twenty-seven percent of infants exhibited WBC antibodies, but only 13 percent actually produced WBC antibodies (passive maternal antibody excluded). Of the WBC antibodies produced by infants, three were against HLA class I and one was against neutrophil-specific antigens; none were linked to adverse effects. CONCLUSIONS: Because infants only rarely produce RBC antibodies, no changes in blood banking practices are necessary for limited-donor-exposure programs. Although the production of WBC antibodies by infants occurs, it seems to be uncommon; thus, the possible benefits, if any, of WBC reduction are uncertain, and further study is required before changes in practice can be justified.

BACKGROUND: Most very low birth weight (

BACKGROUND: Very-low-birthweight infants have typically been given fresh red cells (RBCs), a practice in which aliquots of RBCs for several infants were issued each day from a single unit. Recently, to limit donor exposures, large volumes of RBCs are reserved for the long-term transfusion support of individual infants. STUDY DESIGN AND METHODS: Medical records were examined retrospectively to assess the costs of a limited-donor program for providing RBC transfusions to very-low-birthweight infants. Costs of multiple- and limited-donor programs were compared by using two samples of 30 consecutive infants treated at The University of Iowa Hospitals and Clinics in 1993 and 1997. Effectiveness was evaluated with respect to the number of donor exposures per infant. RESULTS: The cost, in 1997 dollars, of preparing each small-volume transfusion in the multiple-donor program was $27.86 per transfusion, while that in the limited-donor program was $34.83. This difference was largely attributable to use of white cell reduction in association with the limited-donor program in 1997. Eliminating the costs associated with white cell reduction rendered the costs of the limited- and multiple-donor transfusions comparable. The limited-donor program had donor exposures of 2.0 per infant, while the multiple-donor program had 3.6 exposures per infant (p

How platelet (PLT) product characteristics such as dose, source (whole blood derived [WBD] vs. apheresis), storage duration, and ABO matching status affect the risks of transfusion-related adverse events (TRAEs) is unclear. Similarly, more information is needed to define how recipient characteristics affect the frequency of TRAEs after PLT transfusion.In the multicenter Platelet Dose ("PLADO") study, pediatric and adult hematology-oncology patients with hypoproliferative thrombocytopenia were randomized to receive low-dose (LD), medium-dose (MD), or high-dose (HD) PLT prophylaxis for a pretransfusion PLT count of not more than 10 × 10(9) /L. All PLT units (apheresis or WBD) were leukoreduced. Post hoc analyses of PLADO data were performed using multipredictor models.A total of 5034 PLT transfusions to 1102 patients were analyzed. A TRAE occurred with 501 PLT transfusions (10.0%). The most common TRAEs were fever (6.6% of transfusions), allergic or hypersensitivity reactions (1.9%), and sinus tachycardia (1.8%). Patients assigned HD PLTs were more likely than LD or MD patients to experience any TRAE (odds ratio for HD vs. MD, 1.50; 95% confidence interval, 1.10-2.05; three-group comparison p = 0.02). PLT source and ABO matching status were not significantly related to overall TRAE risk. Compared to a patient's first PLT transfusion, subsequent PLT transfusions were less likely to have a TRAE reported, primarily due to a lower risk of allergic or hypersensitivity reactions.The most important PLT unit characteristic associated with TRAEs was PLT dose per transfusion. HD PLTs may increase the risk of TRAEs, and LD PLTs may reduce the risk.

Although the risks of allogeneic blood transfusions are small, it is wise to limit donor exposure whenever possible. A program has been developed in which one donor provided all red cell (RBC) units for each patient awaiting elective surgery. Patients were mostly children who were ineligible for autologous blood donation. Seventy-three patients and 115 donors (mostly parents) entered the program. Of the 115 donors, 90 (78%) were eligible to participate and 25 (22%) were ineligible; 21 were ineligible because of RBC incompatibility. For each of the 73 patients, one eligible donor was selected to donate all RBC units. Preoperative RBC orders were 1 to 2 units for 41 patients and > or = 3 units for 32 patients. Of the 73 donors, 58 (79%) gave all RBC units ordered; 15 (21%) failed to complete all donations, but only 1 because of anemia (hematocrit < 33% [0.33]). Of 73 patients entered, 46 (63%) underwent transfusion, and 27 (37%) did not. Of 46 patients transfused, 38 (83%) received only single-donor RBCs. Thus, the RBC needs of nearly all pediatric elective surgery patients were provided by a single donor for each patient. Single-donor blood programs should be considered for elective surgery patients who are ineligible for autologous blood donation and who would otherwise be exposed to multiple donors.

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.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).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).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.

Background: Historically, paid blood donors were found to transmit hepatitis at higher rates than volunteers. In those older studies, paid donors frequently were recruited from prisons or slum areas–a finding consistent with the belief that monetary payment in itself did not necessarily lead to the high-risk status of commercial blood. Instead, it was the population base from which the donors were recruited that was important. Study Design and Methods: Today, cytapheresis donors are in great demand. Because payment is one incentive that might entice donors to undertake the increased commitment of repeated cytapheresis donation, the results were studied of infectious disease history and laboratory testing performed concurrently in 917 volunteer whole-blood donors and 1240 paid cytapheresis donors, who were enrolled in distinct programs at the DeGowin Blood Center from October 7, 1987, through November 30, 1990. Results: When first, repeat, and overall donations made by these donors were evaluated separately, paid cytapheresis donors were found to exhibit no increase in infectious disease history or test results beyond those of volunteer whole-blood donors. Conclusion: Thus, paid cytapheresis donors, when managed within a formal program, should not necessarily be presumed to be more dangerous than volunteers, from an infectious disease aspect. However, definitive proof of safety (comparison of transfusion-transmitted infection rates in two groups of patients receiving blood components exclusively from either paid cytapheresis or volunteer donors) was not pursued by long- term follow-up studies.

Safe, accurate methods to reliably measure circulating red blood cell (RBC) kinetics are critical tools to investigate pathophysiology and therapy of anemia, including hemolytic anemias. This study documents the ability of a method using biotin-labeled RBCs (BioRBCs) to measure RBC survival (RCS) shortened by coating with a highly purified monomeric immunoglobulin G antibody to D antigen.Autologous RBCs from 10 healthy D+ subjects were labeled with either biotin or (51) Cr (reference method), coated (opsonized) either lightly (n = 4) or heavily (n = 6) with anti-D, and transfused. RCS was determined for BioRBCs and for (51) Cr independently as assessed by three variables: 1) posttransfusion recovery at 24 hours (PTR(24) ) for short-term RCS; 2) time to 50% decrease of the label (T(50) ), and 3) mean potential life span (MPL) for long-term RCS.BioRBCs tracked both normal and shortened RCS accurately relative to (51) Cr. For lightly coated RBCs, mean PTR(24) , T(50) , and MPL results were not different between BioRBCs and (51) Cr. For heavily coated RBCs, both short-term and long-term RCS were shortened by approximately 17 and 50%, respectively. Mean PTR(24) by BioRBCs (84 ± 18%) was not different from (51) Cr (81 ± 10%); mean T(50) by BioRBCs (23 ± 17 days) was not different from (51) Cr (22 ± 18 days).RCS shortened by coating with anti-D can be accurately measured by BioRBCs. We speculate that BioRBCs will be useful for studying RCS in conditions involving accelerated removal of RBCs including allo- and autoimmune hemolytic anemias.