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Background: Leading digit bias is a heuristic whereby humans overemphasize the left‐most digit when evaluating numbers (e.g., 9.99 vs. 10.00). The bias might affect the interpretation of hemoglobin results and influence red cell transfusion in hospitalized patients. Study Design and Methods: Adults who received a red cell transfusion while registered at the University Health Network (Toronto, Canada) between January 1, 2016 and January 1, 2022 (n = 6 years) were included. The primary analysis excluded apheresis, red cell disorders, radiology suites, and operating rooms. The primary comparison was a regression discontinuity analysis of transfusion occurrence above and below the hemoglobin threshold of 79 g/L (local units). Additional analyses tested other leading digit and control thresholds (71, 81, and 91 g/L). Secondary analyses explored temporal covariates and clinical subgroups. Results: A total of 211,872 red cell transfusions were identified over the study period (median pre‐transfusion hemoglobin 76 g/L; interquartile range = 69–92 g/L), with 107,790 inpatient transfusions in the primary analysis. The 79 g/L threshold showed 815 fewer red cell units above the threshold (95% confidence interval [CI]: −1215 to −415). The 69 g/L threshold showed 2813 fewer transfused units (95% CI: −4407 to −1220), and 89 g/L showed 40 fewer units (95% CI: −408 to 328). The effect was accentuated during daytime, weekday, and May–June months, persisted in analyses including all transfusions, and was absent at control thresholds. Conclusion: Leading digit bias might have a modest influence on the decision to transfuse red cells. The findings may inform practice guidelines and quasi‐experimental study design in transfusion research. [ABSTRACT FROM AUTHOR]

Background: Red blood cell exchange is often used prophylactically in patients with sickle cell disease, with the goal to maintain hemoglobin S (HbS) below a target threshold level. We reviewed whether the daily "rate of rise" (RoR) in HbS that occurs between procedures can be used for patient management. For some patients not achieving their HbS goals despite efficient exchanges, the post‐procedure hematocrit (Hct) target is increased to potentially suppress HbS production. This case series explores the utility of this approach, other clinical uses of the daily RoR in HbS, and the factors that influence it. Study Design and Methods: A total of 660 procedures from 24 patients undergoing prophylactic RBC depletion/exchange procedures were included. Laboratory values and clinical parameters were collected and used to calculate the daily RoR in HbS. Factors such as Hct or medications that might influence the RoR in HbS were evaluated. Results: The RoR in HbS varied widely between patients but remained relatively stable within individuals. Surprisingly, this value was not significantly influenced by changes in post‐procedure Hct or concurrent hydroxyurea use. A patient's average RoR in HbS effectively predicted the pre‐procedure HbS at the following visit (R2 = 0.65). Discussion: The RoR in HbS is a relatively consistent parameter for individual patients that is unaffected by medication use or procedural Hct targets and may be useful in determining intervals between procedures. [ABSTRACT FROM AUTHOR]

Background: Special Forces (SF) teams operate in remote environments with limited medical support. As a result, they may need to rely on buddy transfusions to treat bleeding teammates. Considering that 450 mL has no direct impact on their combat performances, it might be tempting to take more blood from a compatible donor to save a hemorrhaging teammate. This study investigates the effect of a 900 mL blood donation on SF operator performance and recovery time following this donation. Study Design and Methods: Participants underwent a multifactorial assessment including measures of physiological parameters, vigilance, and physical performance. Results from the day of blood donation were compared with baseline values obtained 1 week earlier (i.e., immediate effect), as well as repeated testing at 7, 14, and approximately 30 days after blood donation (i.e., recovery period). Results: Hemoglobin levels and heart rate were affected by giving blood. The participants also experienced a significant decrease in physical performance of more than 50% immediately after blood donation. Recovery was slow over the following weeks, remaining significantly different from baseline until full recovery around day 30. However, participants were still able to respond to a simple stimulus and adjust their response, if necessary, even immediately after donating blood. Discussion: A 900 mL blood donation greatly affects the physical fitness of SF operators. A donation may be worthwhile if it is the only life‐saving procedure available and does not endanger the donor's life. The donor would then become a patient and unable to complete the mission. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that gender‐specific hemoglobin thresholds may not be ideal in the surgical population. Thus, preoperative anemia defined as a hemoglobin of <13.0 g/dL is a well‐established risk factor in elective surgery. However, few studies have investigated the specific influence of preoperative hemoglobin within a machine‐learning model using data from an optimized fast‐track surgical setup. Study Design and Methods: A secondary analysis on the specific influence of preoperative hemoglobin level on a machine‐learning model developed for identifying patients at increased risk of a length of stay (LOS) of >4 day or readmissions due to medical complications in fast‐track total hip and knee arthroplasty within a well‐defined fast‐track protocol. To evaluate the effect of hemoglobin on the model we calculated SHaply Additive Explanation (SHAP) values for the 3913 patients from our previous test‐dataset and stratified by gender and total hip and knee arthroplasty, respectively. Results: The study period ran from January 2017 to August 2017. Median LOS was 1 day and mean preoperative Hb was 15.5 g/dL (SD:1.5), lower in women (14.9 vs. 16.2 g/dL) and with 30.5% of women versus 12.0% of men having a Hb of <13.0 g/dL. There was a steep increase in SHAP value with a preoperative Hb < 14.8 g/dL, and irrespective of gender age and procedure type. Discussion: A machine‐learning model found a hemoglobin threshold of <14.8 g/dL for increased risk of impaired recovery, regardless of gender or age, supporting reevaluation of preoperative anemia thresholds in the elective surgical setting. [ABSTRACT FROM AUTHOR]

Background: Anemia in very low birth weight (VLBW) infants is common and frequently managed with red blood cell (RBC) transfusions. We utilized a linked vein‐to‐vein database to assess the role of blood donors and component factors on measures of RBC transfusion effectiveness in VLBW infants. Study Design and Methods: We linked blood donor and component manufacturing data with VLBW infants transfused RBCs between January 1, 2013 and December 31, 2016 in the Recipient Epidemiology Donor Evaluation Study‐III (REDS III) database. Using multivariable regression, hemoglobin increments and subsequent transfusion events following single‐unit RBC transfusion episodes were examined with consideration of donor, component, and recipient factors. Results: Data on VLBW infants (n = 254) who received one or more single‐unit RBC transfusions (n = 567 units) were linked to donor demographic and component manufacturing characteristics for analysis. Reduced post‐transfusion hemoglobin increments were associated with RBC units donated by female donors (−0.24 g/dL [95% confidence interval (CI) −0.57, −0.02]; p =.04) and donors <25 years old (−0.57 g/dL [95% CI −1.02, −0.11]; p =.02). For RBC units donated by male donors, reduced donor hemoglobin levels were associated with an increased need for subsequent recipient RBC transfusion (odds ratio 3.0 [95% CI 1.3, 6.7]; p <.01). In contrast, component characteristics, storage duration, and time from irradiation to transfusion were not associated with post‐transfusion hemoglobin increments. Conclusion: Donor sex, age, and hemoglobin levels were associated with measures of RBC transfusion effectiveness in VLBW infants. Mechanistic studies are needed to better understand the role of these potential donor factors on other clinical outcomes in VLBW infants. [ABSTRACT FROM AUTHOR]

Background: Robust evidence to inform best transfusion management after major oncologic surgery, where postoperative recovery might impact treatment regimens for cancer, is lacking. We conducted a study to validate the feasibility of a larger trial comparing liberal versus restrictive red blood cells (RBC) transfusion strategies after major oncologic surgery. Study Design and Methods: This was a two‐center, randomized, controlled, study of patients admitted to the intensive care unit after major oncologic surgery. Patients whose hemoglobin level dropped below 9.5 g/dL, were randomly assigned to immediately receive a 1‐unit RBC transfusion (liberal) or delayed until the hemoglobin level dropped below 7.5 g/dL (restrictive). The primary outcome was the median hemoglobin level between randomization to day 30 post‐surgery. Disability‐free survival was evaluated by the WHODAS 2.0 questionnaire. Results: 30 patients were randomized (15 patients/group) in 15 months with a mean recruitment rate of 1.8 patients per month. The median hemoglobin level was significantly higher in the liberal group than in the restrictive group: 10.1 g/dL (IQR 9.6–10.5) versus 8.8 g/dL (IQR 8.3–9.4), p <.001, and RBC transfusion rates were 100% versus 66.7%, p =.04. The disability‐free survival was similar between groups: 26.7% versus 20%, p = 1. Discussion: Our results support the feasibility of a phase 3 randomized controlled trial comparing the impact of liberal versus restrictive transfusion strategies on the functional recovery of critically ill patients following major oncologic surgery. [ABSTRACT FROM AUTHOR]

Background: Pathogen reduction technology (PRT) may improve the safety of RBCs for transfusion. As the Czech Republic considers PRT, we asked what effects riboflavin and UV light PRT pre‐freezing has on the post‐thaw recovery and properties of cryopreserved RBCs (CRBCs) after deglycerolization and liquid storage. Study Design and Methods: 24 Group O whole blood (WB) units were leukoreduced and then treated with riboflavin and UV light PRT (Mirasol, Terumo BCT, USA) before cryopreservation (T‐CRBC); 20 similarly‐collected units were untreated controls (C‐CRBC). Units were processed to RBCs and then cryopreserved with 40% glycerol (wt/vol), frozen at −80°C, stored >118 days, reconstituted as deglycerolized RBC units in AS‐3, and stored at 4 ± 2°C for 21 days. One treated unit sustained massive hemolysis during the post‐thaw wash process and was removed from data analysis. The remaining units were assessed pre‐PRT, post‐PRT, and post‐thaw‐wash on days 0, 7, 14, and 21 for hematocrit, volume, hemoglobin per transfusion unit, pH, % hemolysis, hemoglobin in the supernatant, potassium, phosphorus, NH3, osmolality, ATP, and 2,3‐diphosphoglycerate. Results: PRT with leukoreduction caused a 5% loss of RBC followed by a 24% freeze–thaw‐wash related loss for a total 28% loss but treated units contained an average of 45 g of hemoglobin, meeting European Union guidelines for CRBC. T‐CRBCs displayed higher post‐wash hemolysis, potassium, and ammonia concentrations, and lower ATP at the end of storage. Conclusions: Cryopreserved RBCs from Riboflavin and UV light‐treated WB meet the criteria for clinical use for 7 days after thawing and provide additional protection against infectious threats. [ABSTRACT FROM AUTHOR]

Background: Good models of chronic red blood cell (RBC) transfusion can improve care by accurately estimating time‐dependent hemoglobin (Hb) levels and clinically relevant transfusion parameters. Study Design and Methods: A previously derived mathematical model based on overall Hb mass balance (HMB model) with input parameters of transfused units, transfusion efficiency, RBC lifespan, endogenous Hb, and transfusion interval was applied to three separate clinical studies spanning six transfusion conditions across patient populations with myelodysplastic syndrome (MDS) or thalassemia. Results: The HMB model accurately predicted mean pretransfusion Hb levels for each ensemble cohort of patients with thalassemia or MDS. Dynamic changes in Hb levels were modeled as a function of changes in key input parameters. Improving the 24‐h post‐transfusion RBC survival from 72% to 86% can be used to either (1) reduce RBC usage by 15%–20% through longer transfusion intervals or (2) increase pretransfusion [Hb] by 8%–11% while maintaining a constant transfusion interval. Discussion: The endogenous Hb level is introduced in the HMB model which represents the patient's self‐contribution to overall Hb levels via the autologous RBC lifecycle and was estimated to be 5.0 g/dL for patients with MDS or thalassemia. Transfusion therapy approaches and complementary therapeutics can target multiple, unique model inputs while monitoring net, overall impact on transfusion efficacy. Applying the HMB model to fit individual patient Hb fluctuations will be explored in the future. [ABSTRACT FROM AUTHOR]

Background: Deferrals due to low hemoglobin are time‐consuming and costly for blood donors and donation services. Furthermore, accepting donations from those with low hemoglobin could represent a significant safety issue. One approach to reduce them is to use hemoglobin concentration alongside donor characteristics to inform personalized inter‐donation intervals. Study Design and Methods: We used data from 17,308 donors to inform a discrete event simulation model comparing personalized inter‐donation intervals using "post‐donation" testing (i.e., estimating current hemoglobin from that measured by a hematology analyzer at last donation) versus the current approach in England (i.e., pre‐donation testing with fixed intervals of 12‐weeks for men and 16‐weeks for women). We reported the impact on total donations, low hemoglobin deferrals, inappropriate bleeds, and blood service costs. Personalized inter‐donation intervals were defined using mixed‐effects modeling to estimate hemoglobin trajectories and probability of crossing hemoglobin donation thresholds. Results: The model had generally good internal validation, with predicted events similar to those observed. Over 1 year, a personalized strategy requiring ≥90% probability of being over the hemoglobin threshold, minimized adverse events (low hemoglobin deferrals and inappropriate bleeds) in both sexes and costs in women. Donations per adverse event improved from 3.4 (95% uncertainty interval 2.8, 3.7) under the current strategy to 14.8 (11.6, 19.2) in women, and from 7.1 (6.1, 8.5) to 26.9 (20.8, 42.6) in men. In comparison, a strategy incorporating early returns for those with high certainty of being over the threshold maximized total donations in both men and women, but was less favorable in terms of adverse events, with 8.4 donations per adverse event in women (7.0, 10,1) and 14.8 (12.1, 21.0) in men. Discussion: Personalized inter‐donation intervals using post‐donation testing combined with modeling of hemoglobin trajectories can help reduce deferrals, inappropriate bleeds, and costs. [ABSTRACT FROM AUTHOR]

Background: Circulating CD71+ red blood cells (RBCs) have been reported to play an immunomodulatory role in vivo, which may contribute to adverse donor–recipient sex‐mismatched transfusion outcomes. However, it is not clear how CD71+ RBC quantity in red cell concentrates (RCCs) is affected by manufacturing methods and donor factors such as donor sex, donor age, pre‐donation hemoglobin (Hb), venous Hb (Hbv) levels, and donation frequency. Methods: We determined CD71+ RBCs and Hb levels in whole blood (WB) from healthy donors (42 male/38 female). Using small‐scale red cell filtration (RCF) and whole blood filtration (WBF) methods, leukoreduced RCCs were processed from WB samples (n = 6) and the CD71+ RBCs were determined at days 1, 7, and 28. We examined uni‐ and multivariate associations among CD71+ RBCs, donor factors, and manufacturing method. Results: Male donors had a higher CD71+ RBC concentration than females (p <.001), especially male donors aged 17–50 years with 1 or 2 WB donations over the previous 12 months. Donors with a Hbv above 155 g/L had a higher CD71+ RBC concentration than an Hbv level below 140 g/L (p <.05). There was a positive correlation between pre‐donation Hb and CD71+ RBC concentration (Pearson r = 0.41). WBF RCCs had a higher total number of CD71+ RBCs than RCF‐produced RCCs on day 1 (p <.05). Discussion: RCCs have variable numbers of CD71+ RBCs. This makes understanding the impact of donor factors and manufacturing methods on the immunomodulatory effect of CD71+ RBCs critical in exploring donor–recipient sex‐mismatched transfusions. [ABSTRACT FROM AUTHOR]

Background: Preoperative anemia is common and associated with adverse postoperative outcomes. Assessment of hemoglobin concentrations may facilitate optimization prior to surgery. However, phlebotomy‐based hemoglobin measurement may contribute to patient discomfort and iatrogenic blood loss, which makes non‐invasive hemoglobin estimation attractive in this setting. Study Design and Methods: This is a prospective study of adult patients presenting for preoperative evaluation before elective surgery at a tertiary care medical center. The Masimo Pronto Pulse CO‐Oximeter was utilized to estimate blood hemoglobin concentrations (SpHb), which were then compared with hemoglobin concentrations obtained via complete blood count. Receiver operating curves were used to identify SpHb values maximizing specificity for anemia detection while meeting a minimum sensitivity of 80%. Results: A total of 122 patients were recruited with a median (interquartile range) age of 66 (58, 72) years. SpHb measurements were obtained in 112 patients (92%). SpHb generally overestimated hemoglobin with a mean (± 1.96 × standard deviation) difference of 0.8 (−2.2, 3.9) g/dL. Preoperative anemia, defined by hemoglobin <12.0 g/dL in accordance with institutional protocol, was present in 22 patients (20%). The optimal SpHb cut‐point to identify anemia was 13.5 g/dL: sensitivity 86%, specificity 81%, negative predictive value 96%, and positive predictive value 53%. Utilizing this cut‐point, 60% (73/122) of patients could have avoided phlebotomy‐based hemoglobin assessment, while an anemia diagnosis would have been missed in <3% (3/122). Conclusion: The use of SpHb devices for anemia screening in surgical patients is feasible with the potential to reliably rule‐out anemia despite limited accuracy. [ABSTRACT FROM AUTHOR]

Background: Differences in manufacturing conditions using the Haemonetics ACP 215 cell processor result in cryopreserved red cell concentrates (RCCs) of varying quality. This work studied the effect of processing method, additive solution, and storage duration on RCC quality to identify an optimal protocol for the manufacture of cryopreserved RCCs. Materials and methods RCCs were pooled‐and‐split and stored for 7, 14, or 21 days before cryopreservation. Units were glycerolized with the ACP 215 using a single or double centrifugation method. After thawing, the RCCs were deglycerolized, suspended in AS‐3, SAGM, ESOL, or SOLX/AS‐7, and stored for 0, 3, 7, 14, or 21 days before quality testing. Quality assessments included hemoglobin content, hematocrit, hemolysis, adenosine triphosphate (ATP), supernatant potassium, and mean cell volume. Results: Both glycerolization methods produced RCCs that met regulatory standards for blood quality. Dual centrifugation resulted in higher hemoglobin content, fewer processing alerts, and a shorter deglycerolization time than single centrifugation processing. Units processed with AS‐3 and ESOL met regulatory standards when stored for up to 21 days pre‐cryopreservation and 21 days post‐deglycerolization. However, ESOL demonstrated superior maintenance of ATP over RBCs in AS‐3. Some RCCs suspended in SAGM and SOLX exceeded acceptable hemolysis values after 7 days of post‐deglycerolization storage regardless of pre‐processing storage length. Conclusions: When manufacturing cryopreserved RCCs using the ACP 215, dual centrifugation processing with AS‐3 or ESOL additive solutions is preferred, with storage periods of up to 21 days both pre‐processing and post‐deglycerolization. [ABSTRACT FROM AUTHOR]

Background: On-site deferral for low hemoglobin (Hb) is common in most countries and deferral rates commonly vary between 1% and 20%. Blood banks continuously strive to reduce deferral rates as these imply an immediate loss of products, a waste of materials, a waste of staff and donor time, and potential loss of donors. Despite many efforts, the main cause of donor deferral-the variability in hemoglobin measurement outcomes-remains largely unaddressed.Study Design and Methods: Repeated hemoglobin measurements obtained at donor intake were used to estimate the variability in measurement outcomes (measurement variability). This information is incorporated in a new algorithm for donor deferral where the mean hemoglobin level of a donor is used to determine both donor eligibility and the deviance of individual measurement outcomes. The algorithm was tested on a cohort of new Dutch donors that started between 2012 and 2022 to evaluate its impact on the donor deferral rate.Results: Historical data from 439,376 new donors with a deferral rate of 5.3% were analyzed by applying the new donor deferral algorithm. It was found that 92% of all deferrals were unnecessary as Hb levels were within the range of expected measurement variability. Contrarily, it appeared that 460 donors (0.10%) made 704 donations (0.06%) whilst not complying with donor eligibility criteria.Discussion: Not accounting for measurement variability can be shown to not only result in unnecessary on-site deferrals but also results in donations by donors that can be shown not to comply with the legally required minimum Hb levels. [ABSTRACT FROM AUTHOR]

Background: Washing red blood cell (RBC) units prior to transfusion is indicated for certain patients. In the United States, units stored at 1°C-6°C or transported at 1°C-10°C are available for issue up to 24 h, if not used immediately. The washing procedure commonly utilizes room temperature saline resulting in units starting out above the allowed temperature range. This leads to wastage if units are issued and returned too quickly before having a chance to equilibrate in a transport cooler.Study Design and Methods: Here we performed an experimental study of washed RBC quality comparing "ideal" storage conditions in a blood bank refrigerator to a "real-world" simulation of unit transport, including holding in a transport cooler. Twelve RBC units were washed and allocated evenly into either condition.Results: Measurements at 0, 1, 3, 6, 12, and 24 h post-washing revealed that placement in a transport cooler was associated with higher unit temperature prior to 12 h (p = .013) with a maximum difference of 9.3°C. Despite this difference, several measures of unit quality including extracellular potassium, pH, lactate, and free hemoglobin were indistinguishable between conditions (p = .382, .224, .286, .691, respectively). We selected half of the tested units from our irradiated inventory and confirmed increased potassium leak (p < .001) and accumulation of free hemoglobin (p = .012) in irradiated units.Discussion: Washed units stored under approved transport conditions are acceptable to return to inventory up to 24 h after washing and we provide a prediction interval-based temperature threshold for rejecting these units, permitting reduced waste. [ABSTRACT FROM AUTHOR]

Background: Blood donation is associated with a loss of hemoglobin (Hb)‐bound iron. Hb levels recover relatively fast by using stored iron. However, it takes more time to replenish iron stores, potentially resulting in iron deficiency. Study design Hb and ferritin levels were measured in 5056 new, first‐time, and repeat whole blood donors. We investigated whether increasing numbers of donations are associated with lower ferritin levels. Furthermore, we tested whether low ferritin levels are associated with low‐Hb deferral at the subsequent donation attempt by performing logistic regression adjusted for age and stratified by sex. Results: Whereas mean Hb levels are relatively stable, ferritin levels significantly decrease with increasing numbers of donations and were approximately 50% lower for donors with >50 donations compared with those with 2–10 donations. Despite the poor correlation of ferritin and Hb levels, cross‐sectional, iron‐deficient donors (ferritin <15 ng/ml) had 21.8 (8.5–55.6) higher odds in men, 10.1 (6.1–16.5) in premenopausal women, and 11.7 (5.2–26.4) in postmenopausal women for Hb deferral at a subsequent visit. Discussion: To conclude, repeated donations may induce iron deficiency, which corresponds with an over tenfold increased risk of having insufficiently restored Hb levels at a subsequent donation attempt. Longer donation intervals and/or higher dietary or supplemental iron intake are warranted to prevent accumulated iron depletion and subsequent low‐Hb deferral in whole blood donors. [ABSTRACT FROM AUTHOR]

Background: Blood donor screening includes tests using capillary blood, which is usually obtained by finger pricking using a lancet; however, the lancet has some shortcomings, such as skin puncture pain and needle stick injury. Recently, laser lancing devices for finger‐prick sampling have been developed. We compared capillary blood Hb (cHb) levels and blood typing results obtained using a laser lancing device with those obtained using a lancet. Study design and methods: cHb levels, blood typing results, and skin puncture pain scores were assessed in 191 participants. Finger‐prick sampling was performed using LMT‐1000 (LaMeditech, Seoul, Korea) and a lancet on the same finger on different hands. Paired venous Hb (vHb) levels were assessed in 103 participants using an automated hematology analyzer and compared with the cHb levels obtained using both lancing devices. Results: The paired cHb results obtained with the laser lancing device and lancet showed a strong correlation (r = 0.927, p <.001) without any significant difference (p =.113) and a substantial agreement (κ = 0.654) for the identification of participants with a low Hb level (<12.5 g/dl). cHb levels were significantly higher than vHb levels with both lancing devices (mean differences: 0.27–0.43 g/dl). The results of blood typing using the laser lancing device showed 100% accuracy. Use of the laser lancing device showed significantly lower skin puncture pain scores (p <.001). Conclusion: Use of a laser lancing device for capillary Hb measurement and blood typing showed accurate results, with significantly reduced skin puncture pain. Laser lancing devices could be feasible for donor screening tests. [ABSTRACT FROM AUTHOR]

We read with interest the recent study by Hajjal and colleagues which effectively assessed the annual detection rate and cost of pre-transfusion sickle cell trait (SCT) testing of red blood cell (RBC) units in a Canadian pediatric hospital.[1] These findings have profound implications on how pre-transfusion testing is performed in various patient populations, specifically individuals with sickle cell disease (SCD), neonates, and intrauterine transfusion. Moreover, approximately half of HbS+ donor units do not successfully migrate through the leukoreduction filter during manufacturing and are discarded.[3] Thus, it is difficult to interpret the low incidence rate of solubility testing given these donor pool factors. Blood donor recruitment and retention are expensive, and a positive HbS solubility test may result in greater costs. [Extracted from the article]

When investigating the effect voxelotor treatment might have on future HPLC hemoglobin fractionations, we learned about potential issues associated with voxelotor interference on HPLC hemoglobin fractionation assays, as described above. After confirming the presence of unresolved peaks in the patient sample that were characteristic of voxelotor interference, we implemented an approach (Figure 1) to mitigate the effect of the interference that is similar to a previously published approach.1 GLO:1YB/01jun21:trf16405-fig-0001.jpg PHOTO (COLOR): 1 Hemoglobin fractionation for patient taking voxelotor workflow gl When a quantitative hemoglobin fractionation is requested, an automated order inquiry now asks the provider if the patient is taking voxelotor. Voxelotor prescribing information describes that voxelotor may interfere with high-performance liquid chromatography (HPLC) and recommends performance of hemoglobin quantitation using HPLC when patients are not taking the drug "[i]f precise quantitation of Hb species is required."3 Published studies have demonstrated voxelotor interference in hemoglobin fractionation assays due to the formation of voxelotor-hemoglobin complexes.1,2 The voxelotor-hemoglobin complexes cause resolved or unresolved interfering peaks in capillary electrophoresis and HPLC measurement procedures. [Extracted from the article]

Background: Hemolysis releases toxic cell‐free hemoglobin (Hb), heme, and iron, which overwhelm their natural scavenging mechanisms during acute or chronic hemolytic conditions. This study describes a novel strategy to purify a protein cocktail containing a comprehensive set of scavenger proteins for potential treatment of hemolysis byproducts. Study Design and Methods: Tangential flow filtration was used to purify a protein cocktail from Human Cohn Fraction IV (FIV). A series of in vitro assays were performed to characterize composition and biocompatibility. The in vivo potential for hemolysis byproduct mitigation was assessed in a hamster exchange transfusion model using mechanically hemolyzed blood plasma mixed with the protein cocktail or a control colloid (dextran 70 kDa). Results: A basis of 500 g of FIV yielded 62 ± 9 g of a protein mixture at 170 g/L, which bound to approximately 0.6 mM Hb, 1.2 mM heme, and 1.2 mM iron. This protein cocktail was shown to be biocompatible in vitro with red blood cells and platelets and exhibits nonlinear concentration dependence with respect to viscosity and colloidal osmotic pressure. In vivo assessment of the protein cocktail demonstrated higher iron transport to the liver and spleen and less to the kidney and heart with significantly reduced renal and cardiac inflammation markers and lower kidney and hepatic damage compared to a control colloid. Discussion Taken together, this study provides an effective method for large‐scale production of a protein cocktail suitable for comprehensive reduction of hemolysis‐induced toxicity. [ABSTRACT FROM AUTHOR]

Background: Though weight is a major consideration when transfusing blood in pediatric patients, it is generally not considered when dosing transfusions in adults. We hypothesized that the change in hemoglobin (Hb) concentration is inversely proportional to body weight when transfusing red blood cells (RBC) in adults.Methods: A total of 13,620 adult surgical patients at our institution were assessed in this retrospective cohort study (2009-2016). Patients were stratified based on total body weight (kg): 40-59.9 (16.6%), 60-79.9 (40.4%), 80-99.9 (28.8%), 100-119.9 (11.3%), and 120-139.9 (2.9%). The primary outcome was the change in Hb per RBC unit transfused. Subgroup analyses were performed after stratification by sex (male/female) and the total number of RBC units received (1/2/≥3 units). Multivariable models were used to assess the association between weight and change in Hb.Results: As patients' body weight increased, there was a decrease in the mean change in Hb per RBC unit transfused (40-59.9 kg: 0.85 g/dL, 60-79.9 kg: 0.73 g/dL, 80-99.9 kg: 0.66 g/dL, 100-119.9 kg: 0.60 g/dL, 120-139.9 kg: 0.55 g/dL; p < .0001). This corresponded with a 35% difference in the change in Hb between the lowest and highest weight categories on univariate analysis. Similar trends were seen after subgroup stratification. On multivariable analysis, for every 20 kg increase in patient weight, there was a ~6.5% decrease in the change in Hb per RBC unit transfused (p < .0001).Conclusions: Patient body weight differentially impacts the change in Hb after RBC transfusion. These findings justify incorporating body weight into the clinical decision-making process when transfusing blood in adult surgical patients. [ABSTRACT FROM AUTHOR]

Background: To prevent (negative consequences of) temporary deferral due to low hemoglobin, the Dutch national blood service Sanquin introduced a ferritin monitoring policy in 2017. Ferritin is measured after the donation (as opposed to before donation for hemoglobin), and low ferritin levels lead to deferral of 6 (ferritin 15‐30 ng/mL) or 12 months (ferritin <15 ng/mL). We explored the consequences of this policy on donor behavior and availability. Study Design and Methods: We included all Dutch whole blood donors who made a donation (attempt) between 13 November and 31 December 2017. At that point, the ferritin monitoring policy was randomly implemented in 8 of 29 regional clusters of collection centers. We extracted information from Sanquin's donor database about donors' deferrals, subsequent donation attempts, and donation cessation (up to 31 December 2019). Donors deferred for low ferritin were compared to those deferred for low hemoglobin or other reasons, as well as to donors who were not deferred. Results: A total of 55 644 donors were included (11% deferred). For donor behavior, we found that donors deferred for low ferritin less often unsubscribed and switched to other donation types, yet also made fewer donations in the follow‐up period. For availability, we found they were less often deferred, yet they were unavailable to donate for a longer period. Conclusion: Results suggest that the implementation of a ferritin monitoring policy may lead to a decrease in donor availability and reduced donations. However, the policy is successful in retaining more donors and reducing low hemoglobin deferrals. [ABSTRACT FROM AUTHOR]

Background: A patientʼs hemoglobin is typically expected to rise by 1 g/dL/unit transfused PRBCs. However, it has been theorized that mechanisms such as hyperbilirubinemia and splenomegaly might lead to either a direct lysis or sequestration of red blood cells that could decrease this proportionate response. Study Design and Methods: Patients with resolved GI bleeding but still requiring transfusion to correct anemia were compared in cirrhosis and control groups. A retrospective chart review between 2015 and 2020 was conducted at a single institution. Data collected included age, sex, BMI, GI bleed diagnosis, number of PRBCs transfused, presence of splenomegaly and spleen size, alcohol use history, type of cirrhosis, MELD‐Na at admission, GFR, and pre‐and post‐transfusion labs: total bilirubin, ALT, hemoglobin, hematocrit. A logic regression was performed for each group looking at which factors were associated with a successful response (defined as >0.9 g/dL hemoglobin per unit transfused). Results: Mean change in hemoglobin was 0.77 g/dL in patients with cirrhosis compared to 1.46 g/dL in patients without (P <.001, N = 103). Odds ratios for presence of splenomegaly (0.22, N = 78) and female sex (4.39, N = 102) in predicting adequate response (>0.9 g/dL/unit) were both significant (P =.002) as well as portal hypertensive bleed diagnosis (0.28, N = 85, P =.0015). Factors that did not contribute included: age, race, BMI, alcohol use, GFR, change in ALT, and change in total bilirubin. Conclusions: Patients with cirrhosis have an approximately 50% decreased response to transfusion with PRBCs after resolution of a gastrointestinal bleed in comparison to patients without cirrhosis. Risk factors included splenomegaly, portal hypertension, and male sex. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin (Hb)‐based oxygen (O2) carriers (HBOCs) are being developed as alternatives to red blood cells and blood when these products are unavailable. Clinical trials of previous HBOC generations revealed side effects, including hypertension and vasoconstriction, that were not observed in preclinical studies. Large molecular weight (MW) polymerized bovine Hb (PolybHb) represents a new class of HBOC with promising results. We evaluated the safety profile of PolybHb after an exchange transfusion (ET) in guinea pigs (GPs). This study compares changes in indices of cardiac, inflammatory, and organ function after ET with high (R‐state) and low (T‐state) O2 affinity PolybHb with high MW. Study Design and Methods: Guinea pigs underwent a 20% ET with PolybHb. To assess the implication of PolybHb ET on the microcirculation, hamsters instrumented with a dorsal window chamber were subjected to a similar volume ET. Results: T and R‐state PolybHb did not induce significant alterations in cardiac function. T‐state PolybHb induced mild vasoconstriction shortly after transfusion, while R‐state did not have acute effects on microvascular tone. Conclusion: Large MW PolybHbs were found to be safe and efficacious in increasing O2 carrying capacity and the O2 affinity of the PolybHb did not affect O2 delivery or extraction by tissues in relevant preclinical models. In conclusion, these results suggest that both T‐state and R‐state PolybHb are safe and do not impair O2 delivery. The results are encouraging and support further evaluation of high MW PolybHbs and their future feasibility compared to allogenic blood in a trauma model. [ABSTRACT FROM AUTHOR]

Background: Red blood cell (RBC) transfusion is common in surgical patients, yet optimal transfusion targets are incompletely defined in the perioperative period. Hemoglobin levels at the time of hospital discharge may provide insight into transfusion practices, anemia management, and patient outcomes. Study Design and Methods: This is an observational cohort study of adults receiving RBC transfusion during noncardiac surgery from 2010 to 2014. Multivariable regression was used to assess the relationships between hospital discharge hemoglobin concentrations, anemia severity (severe: <8 g/dL; moderate: 8‐10 g/dL; mild/none: ≥10 g/dL), and clinical outcomes, including a primary outcome of 30‐day hospital readmission and secondary outcomes of posthospitalization RBC transfusion, composite stroke or myocardial infarction, and mortality. Results: A total of 3129 patients were included: 165 (5%) with severe discharge anemia, 1962 (63%) moderate, and 1002 (32%) with mild/none. Five hundred ninety‐two (19%) were readmitted, with the highest rates observed with severe anemia (26% vs 19% for mild/none). Readmissions were not significantly different after multivariable adjustment (overall P =.216); however, in those receiving postoperative intensive care, severe anemia was associated with increased readmission rates (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.09‐2.71; reference mild/none]. Posthospitalization RBC transfusion rates were highest with severe anemia (25% vs 10% for mild/none; adjusted HR, 2.2; 95% CI, 1.5‐3.3; P <.001). There were no significant differences in composite stroke/myocardial infarction, or mortality. RBC transfusion volumes did not modify anemia‐outcome relationships. Conclusion: Hospital discharge hemoglobin values for transfused surgical patients were not associated with hospital readmission rates except for those receiving postoperative intensive care. Further evaluation is warranted to understand downstream consequences of postsurgical anemia. See editorial on page 2168–2170, in this issue [ABSTRACT FROM AUTHOR]

Backgrounds: Intravenous transfusion sometimes encounters difficulty under prehospital conditions when peripheral vessels are collapsed and inaccessible. We investigated whether the cellular type hemoglobin-based oxygen carriers (Hemoglobin Vesicles: HbVs) allow intraosseous administration into blood circulation for the resuscitation of rabbits with severe hemorrhagic shock.Study Design and Methods: New Zealand white rabbits (2.5 kg average) were set in severe hemorrhagic shock [mean arterial pressure (MAP): 21 ± 2 mm Hg, Hb 5.1 ± 0.8 g/dL]. Immediately thereafter, 12 mL/kg of HbVs, 5% human serum albumin (HSA), autologous whole blood (WB), stored red blood cells (RBCs) or 36 mL/kg of Lactated Ringer's (LR) were intraosseously transfused, followed by an additional intraosseous transfusion with 8 mL/kg of HSA (following HbV, HSA or stored RBC transfusion), or WB or 24 mL/kg of LR (following LR transfusion), respectively.Results: Intraosseous transfusion of HbVs increased MAP (48 ± 9 mm Hg) and improved hypohemoglobinemia (7.1 ± 0.6 g/dL) as well as WB or RBC transfusion. In contrast, neither HSA nor LR improved hemodynamics or Hb levels. Seven out of 10 rabbits receiving HbVs survived for 24 hours, while only one out of 10 rabbits receiving LR survived (WB and RBC; 100% survivals, HSA; 30% survival).Conclusions: Intraosseous infusion of HbVs might be an effective initial treatment to maintain hemodynamics during acute hemorrhagic shock. This approach could be used in emergency situations in which access to peripheral vessels is difficult. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic severe iron deficiency anemia is a common finding in subjects admitted to the outpatient anemia clinic. Although the condition can be easily be reversed with intravenous iron (IVI) therapy and several guidelines have suggested a restrictive threshold for using transfusion in hemodynamically stable patients, transfusion is often the rule in clinical practice. This study describes clinical practice results of IVI therapy without transfusion.Study Design and Methods: In this multicenter retrospective observational study, data of severely anemic outpatients treated only with high-dose IVI with ferric carboxymaltose were collected. Inclusion criteria were hemoglobin (Hb) level of less than 7.0 g/dL and ferritin level of less than 30 ng/mL or mean corpuscular volume of less than 75 fL.Results: Overall, 303 patients referred to the anemia clinic mainly from primary health care centers (46.2%) or the emergency department (28.7%) met the inclusion criteria. Median (interquartile range [IQR]) age was 47 (37-62) years and 84.5% were female. The median (IQR) Hb concentration at first visit was 6.5 (6.1-6.8) g/dL, 64 patients (21.1%) presented with a Hb level of less than 6.0 g/dL at diagnosis, and 11 of them (3.6%) had extreme anemia (Hb ≤ 5 g/dL). Gynecologic and gastroenteric bleeding were the main cause. After a mean IV administration of 1500 mg of iron, the Hb increased by a median of 5.7 g/dL. Thirteen patients experienced only mild side effects.Conclusions: In chronic very severe sideropenic anemias, third-generation IVI is effective and safe for quick correction and avoidance of red blood cell transfusion. These results suggest that more specific guidelines for this clinical setting are warranted. [ABSTRACT FROM AUTHOR]

Background: This study evaluated blood components processed by the platelet rich plasma (PRP) method from fresh whole blood (FWB) treated with a pathogen reduction technology (PRT). The effects of storage temperature on PRT treated platelet concentrates (PCs) were also examined.Study Design and Methods: PRT was performed using riboflavin and ultraviolet light on FWB in citrate phosphate dextrose anticoagulant. Following PRT, red blood cells (RBCs), PCs, and plasma for fresh frozen plasma (FFP), were isolated by sequential centrifugation. RBCs were stored at 4°C, FFP at -80°C, and PC at 22°C or at 4°C. Components were assayed throughout their storage times for blood gases, chemistry and CBC, hemostatic function as well as platelet (PLT) and RBC integrity.Results: Component processing following PRT resulted in a significant drop in platelet recovery. Most PRT-PC bags fell below AABB guidelines for platelet count. PRT-PC also showed a decrease in clot strength and decreased aggregometry response. Platelet caspases were activated by PRT. Storage at 4°C improved platelet function. In PRT-FFP, prothrombin time and partial thromboplastin time (PT and aPTT) were prolonged; factors V, VII, VIII, and XI, protein C, and fibrinogen were significantly decreased. Free hemoglobin was elevated two-fold in PRT-RBC.Conclusion: Blood components isolated by the PRP method from PRT-treated WB result in a high percentage of PC that fail to meet AABB guidelines. FFP also shows diminished coagulation capacity. However, PRT-RBC are comparable to control-RBC. PRT-WB retains acceptable hemostatic function but alternatives to the PRP method of component separation may be more suitable. [ABSTRACT FROM AUTHOR]

Background: Recent publications have reported conflicting results regarding the role of blood donor tobacco use on hemoglobin (Hb) levels in patients after red blood cell (RBC) transfusion. We examined associations and interactions between donor, component, and recipient factors to better understand the impact of donor smoking on transfusion outcomes.Study Design and Methods: We linked blood donor and component manufacturing data, including self-reported cigarette smoking, with a cohort of patients transfused RBCs between 2013 and 2016. Using multivariable regression, we examined Hb increments and subsequent transfusion requirements after single-unit RBC transfusion episodes, adjusting for donor, component, and recipient factors.Results: We linked data on 4038 transfusion recipients who received one or more single-unit RBC transfusions (n = 5086 units) to donor demographic and component manufacturing characteristics. Among RBC units from smokers (n = 326), Hb increments were reduced after transfusion of gamma-irradiated units (0.76 g/dL; p = 0.033) but not unirradiated units (1.04 g/dL; p = 0.54) compared to those from nonsmokers (1.01 g/dL; n = 4760). In parallel with changes in Hb levels, donor smoking was associated with the receipt of additional RBC transfusions for irradiated (odds ratio [OR], 2.49; p = 0.01) but not unirradiated RBC units (OR, 1.10; p = 0.52).Conclusion: Donor smoking was associated with reduced Hb increments and the need for additional transfusions in recipients of gamma-irradiated RBC units. Additional research is needed to better understand interactions between donor, component, and recipient factors on efficacy measures of RBC transfusion. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin-Based Oxygen Carriers (HBOCs) can act as an "oxygen bridge" in acute severe anemia when transfusion is indicated, but not possible. We present data on 10 Expanded Access (EA) patients treated with high cumulative doses of Hemopure (HBOC-201), to assess the ability of HBOC-201 to safely treat life threatening anemia in situations where high volumes of product were administered over an extended period of time.Study Design and Methods: Inclusion in this study required that the patient receive at least 10 units of HBOC-201 between 2014 and 2017 under the FDA-sanctioned EA program. Depending on a patient's geographical location, treatment with HBOC-201 was obtained through either a single patient emergency Investigational New Drug (IND) application, or an intermediate size population IND. Of the 41 patients who were treated during this period, 10 patients received 10 or more units of the product. Data were obtained from medical records.Results: Treatments with HBOC-201 started within 24 hours of signing consent and were administered at an average rate of 1.99 (SD 0.17) units per day over a mean of 8.2 days (SD 2.9), during which patients received on average 16.2 units (SD 5.7 units) of HBOC-201. The median pre-treatment nadir corpuscular hemoglobin (Hb) concentration was 3.3 (SD 0.9) g/dL and post-treatment Hemoglobin was 7.3 (SD 1.7) g/dL. Common side effects included methemoglobinemia, gastrointestinal symptoms, and hypertension. However, no product-related serious adverse events (SAEs) were noted. All patients survived.Conclusions: Administration of HBOC-201 over an extended period is a feasible and safe oxygen bridge for severely anemic patients who cannot be transfused with RBC. [ABSTRACT FROM AUTHOR]

Background: Some people rapidly develop iron deficiency anemia following blood donation, while others can repeatedly donate without becoming anemic.Methods: Two cohorts of blood donors were studied. Participants (775) selected from a 2-year longitudinal study were classified into six analysis groups based on sex, donation intensity, and low hemoglobin deferral. Associations with iron supplement use, cigarette smoking, and four genetic variants of iron metabolism were examined at enrollment and with longitudinal regression models. An unbiased assessment of genetic variability and ability to repeatedly donate blood without experiencing low hemoglobin deferral was conducted on participants (13,403) in a cross-sectional study who were examined by genome wide association (GWA).Results: Behaviors and genetic variants were associated with differences in hemoglobin and ferritin change following repeated donation. At least weekly iron supplement use was associated with improved status in first-time donors, while daily use was associated with improved status in high-intensity donors. Cigarette smoking was associated with 0.5 g/dL increased hemoglobin in high-intensity donors. A736V in TMPRSS6 was associated with a rapid drop in hemoglobin and ferritin in first-time females following repeated donation. Conversely, the protective TMPRSS6 genotype was not enriched among high-intensity donors. H63D in HFE was associated with increased hemoglobin in female high-intensity donors. However, no differences in genotype between first-time and high-intensity donors were found in GWA analyses.Conclusion: Behavioral and genetic modifiers contributed to first-time donor hemoglobin and iron status, while iron supplement use was more important than underlying genetics in high-intensity donors. [ABSTRACT FROM AUTHOR]

Background: Red blood cell (RBC) transfusion support is essential in patients with acute leukemia (AL). A restrictive RBC transfusion approach is assumed to be safe for most individuals with AL. The aim of this audit was to assess RBC transfusion appropriateness in AL patients at an academic center.Study Design and Methods: RBC transfusions in acute lymphoblastic leukemia and acute myeloid leukemia patients of all ages between January 1, 2013, and March 31, 2019, were analyzed for adherence to evidence-based criteria. Transfusion appropriateness was compared among ordering specialties, patient locations, and hematologic diagnoses. Pretransfusion hemoglobin was compared between categories. Overtransfusion rates were also analyzed. Descriptive statistics and categorical and numerical tests were employed to determine statistical significance.Results: A total of 510 RBC transfusions were received by 133 AL patients in the departments of internal medicine, hematology, and pediatrics. Overall, 84.5% were appropriate according to established criteria. Internal medicine was the ordering department with the highest rate of appropriateness (88.1%). The outpatient clinic was the location with the highest adherence (85.9%), whereas the intensive care unit had the lowest (70%; p = 0.03). The reasons for most appropriate and inappropriate transfusions were asymptomatic anemia with a hemoglobin below (60.6%) or above (69.6%) 7 g/dL in patients without cardiac disease, respectively. Overtransfusion was present in 22% of episodes.Conclusion: RBC transfusion in AL patients reflected good adherence to guidelines. However, continuing education in transfusion medicine and prospective chart auditing are needed to improve adherence to established guidelines. [ABSTRACT FROM AUTHOR]

Background: Determination of blood donor hemoglobin (Hb) levels is a pre-requisite to ensure donor safety and blood product quality. We aimed to identify Hb measurement practices across blood donation services and to what extent differences associate with low-Hb deferral rates.Methods: An online survey was performed among Biomedical Excellence for Safer Transfusion (BEST) Collaborative members, extended with published data. Multivariable negative-binomial regression models were built to estimate adjusted associations of minimum donation intervals, Hb cut-offs (high, ≥13.5 g/dL in men or ≥ 12.5 g/dL in women, vs. lower values), iron monitoring (yes/no), providing or prescribing iron supplementation (yes/no), post-versus pre-donation Hb measurement and geographical location (Asian vs. rest), with low-Hb deferral rates.Results: Data were included from 38 blood services. Low-Hb deferral rates varied from 0.11% to 8.81% among men and 0.84% to 31.85% among women. Services with longer minimum donation intervals had significantly lower deferral rates among both women (rate ratio, RR 0.53, 95%CI 0.33-0.84) and men (RR 0.53, 95%CI 0.31-0.90). In women, iron supplementation was associated with lower Hb deferral rates (RR 0.47, 95%CI 0.23-0.94). Finally, being located in Asia was associated with higher low-Hb deferral rates; RR 9.10 (95%CI 3.89-21.27) for women and 6.76 (95%CI 2.45-18.68) for men.Conclusion: Differences in Hb measurement and eligibility criteria, particularly longer donation intervals and iron supplementation in women, are associated with variations in low-Hb deferral rates. These insights could help improve both blood donation service efficiency and donor care. [ABSTRACT FROM AUTHOR]

Background: Pediatric patients with sepsis in intensive care units are at high risk of developing anemia, which might have adverse effects on their prognosis. This study aimed to evaluate the impact of red blood cell (RBC) transfusion on the outcomes of patients admitted to a pediatric intensive care unit (PICU) with sepsis.Methods: We conducted a prospective randomized clinical trial, enrolling 67 children, aged 2 to 144 months who were admitted to a PICU with a new episode of sepsis from November 2017 to April 2018. Patients were allocated randomly to two groups: Group 1, liberal transfusion strategy group, including 33 patients who had initial hemoglobin (Hb) between 7 or greater and less than 10 g/dL and received an RBC top-up transfusion to 12 g/dL; and Group 2, restrictive strategy group, including 34 patients who had the same Hb range and did not receive RBCs. Patients with Hb less than 7 or greater than 10 g/dL were excluded.Results: Of 33 patients who received liberal transfusions, 31 (93.94%) required ventilation, and 29 (87.88%) had multiorgan dysfunction. They had a significantly lengthier hospital stay and a higher incidence of acute respiratory distress syndrome and acute lung injury. Moreover, mortality was significantly higher in the liberal transfusion group (42.4% vs. 17.6%).Conclusions: Compared to the restrictive transfusion strategy, liberal transfusion might be associated with a worse outcome. However, the possible role of other known and unknown confounding factors and minor protocol violations should be taken into consideration. We recommend minimizing factors worsening anemia in PICU patients to reduce the need for transfusion. [ABSTRACT FROM AUTHOR]

Background: Turbidity tests are commonly used for screening blood units for the presence of sickle cell trait (SCT) before transfusion to specific patient populations, based on recommendations of the AABB. In this pilot study, we evaluate a new method for screening blood donors and blood units for the presence of sickle hemoglobin.Study Design and Methods: This study was based at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Study participants were approached consecutively between July 24, 2016, and August 8, 2016. Blood donors, control individuals, and known patients with sickle cell disease (SCD) were tested using both a point-of-care testing technology (Sickle SCAN, Biomedomics, Inc.) and hemoglobin capillary electrophoresis (HEP). Corresponding blood units were also tested using Sickle SCAN.Results: A total of 200 donors, 13 blood units, and 57 patients and controls were included. Sensitivity and specificity of Sickle SCAN for detection of SCT and SCD was 100%, when compared to HEP as the gold standard.Conclusion: Sickle SCAN is a rapid test that shows high sensitivity and specificity for identification of hemoglobin S among blood donors and when used for testing blood units. [ABSTRACT FROM AUTHOR]

Background: Many children with sickle cell disease (SCD) indicated for adenotonsillectomy receive pre-operative transfusion therapy, either simple or exchange transfusion, in order to reduce surgical and sickle cell disease-related complications.Subjects and Methods: This is a prospective randomized controlled clinical trial aiming to compare between preoperative simple transfusion and no transfusion in pediatric patients with sickle SCD admitted in Sultan Qaboos University Hospital, Muscat, Oman for adenotonsillectomy during the period from January 2014 through June 2018. They were randomly assigned into two arms (simple transfusion and no transfusion).Results: Postoperative SCD-related complications have been encountered in 6 out of 138 patients (4.3%). There was no statistically significant difference between the two studied groups as regards the development of surgical or SCD-related complications (p = 0.6 and 0.8 respectively). The length of postoperative hospital stay was comparable in the two groups. (p = 0.607). SCD-related complications occurred exclusively in cases with homozygous sickle anemia (4 out of 81 = 4.9%).Conclusion: Sickle cell disease patients with a hemoglobin level above 7.5 g/dL do not need PRBCs transfusion prior to adenotonsillectomy. This approach did not increase the risk of postoperative surgical or SCD-related complications. [ABSTRACT FROM AUTHOR]

Background: Objective measures to assess the need for transfusion in chronic anemia are lacking. Near-infrared spectroscopy may be used, but there is wide variability. Assessment of muscle oxygen saturation (SmO2 ) during exercise could be used to measure the impact of anemia on performance of everyday activities.Study Design and Methods: Hematology patients and controls were recruited to undertake a 6-minute walk test (6MWT) and a 20-second isometric handgrip exercise. Muscle oxygen saturation in the exercising muscles was measured before and during exercise. Changes in saturation during exercise were described. Correlations between identified variables, hemoglobin concentration, and 6MWT distance were undertaken. The effect of transfusion was assessed on a transfused subset.Results: There were 95 sets of exercises conducted in 74 participants. Baseline SmO2 correlated with hemoglobin concentration and negatively with 6MWT distance. Paradoxically, a higher hemoglobin was associated with a greater SmO2 fall during the 6MWT, likely due to greater consumption from improved walk distances. The fall in SmO2 was independent of hemoglobin during isometric contraction, although levels were lower during contraction due to the lower starting SmO2 . There was a longer time to peak SmO2 during recovery following isometric exercise in anemia. There were 17 paired tests following a change in hemoglobin, with SmO2 not predicting improvement in those who had improved exercise capacity.Conclusion: While baseline SmO2 correlated with hemoglobin concentration, the correlation was not strong enough to predict transfusion requirements. Recovery after isometric forearm contraction correlated with hemoglobin and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: During sepsis, higher plasma cell-free hemoglobin (CFH) levels portend worse outcomes. In sepsis models, plasma proteins that bind CFH improve survival. In our canine antibiotic-treated Staphylococcus aureus pneumonia model, with and without red blood cell (RBC) exchange transfusion, commercial human haptoglobin (Hp) concentrates bound and compartmentalized CFH intravascularly, increased CFH clearance, and lowered iron levels, improving shock, lung injury, and survival. We now investigate in our model how very high CFH levels and treatment time affect Hp's beneficial effects.Materials and Methods: Two separate canine pneumonia sepsis Hp studies were undertaken: one with exchange transfusion of RBCs after prolonged storage to raise CFH to very high levels and another with rapidly lethal sepsis alone to shorten time to treat. All animals received continuous standard intensive care unit supportive care for 96 hours.Results: Older RBCs markedly elevated plasma CFH levels and, when combined with Hp therapy, created supraphysiologic CFH-Hp complexes that did not increase CFH or iron clearance or improve lung injury and survival. In a rapidly lethal bacterial challenge model without RBC transfusion, Hp binding did not increase clearance of complexes or iron or show benefits seen previously in the less lethal model.Discussion: High-level CFH-Hp complexes may impair clearance mechanisms and eliminate Hp's beneficial effect during sepsis. Rapidly lethal sepsis narrows the therapeutic window for CFH and iron clearance, also decreasing Hp's beneficial effects. In designing clinical trials, dosing and kinetics may be critical factors if Hp infusion is used to treat sepsis. [ABSTRACT FROM AUTHOR]

Background: The number of red blood cell units transfused per capita in China is lower than in western countries and the reason(s) for the difference is unknown.Study Design and Methods: We randomly chose 5050 transfused patients from five Chinese hospitals. We compared transfused cases to nontransfused controls matched for the same underlying diagnosis. We assessed the pretransfusion hemoglobin (Hb) trigger and other clinical characteristics associated with transfusion. After stratifying by underlying disease, we compared pretransfusion Hb level in Chinese hospitals to 12 US hospitals.Results: In 5050 patients who received transfusion, the pretransfusion Hb levels were lower in medical (6.3 g/dL) compared to surgical patients receiving transfusion postoperatively (8.1 g/dL). In patients with nonsurgical diagnoses, the pretransfusion Hb was much lower than that in the United States; the difference in mean Hb level varied by underlying diagnosis from 0.4 to 1.8 g/dL. In case-control analysis of cases (n = 1356) compared to controls (n = 1201), the pretransfusion Hb showed the strongest association with transfusion. Compared to 10 g/dL, the odds ratio (95% confidence interval) for pretransfusion Hb of 7 to 7.9 g/dL was 37.7 (24.8-57.4).Conclusion: Transfusion triggers in five Chinese hospitals appear comparable to those in the United States for surgical patients; however, medical patients have lower pretransfusion Hb levels (approx. 6 g/dL). Of the factors assessed, the pretransfusion Hb was most strongly associated with transfusion. The clinical impact of lower transfusion thresholds used in China is unknown. [ABSTRACT FROM AUTHOR]

Background: Patients with cancer or chronic hematologic disorders frequently receive red blood cell (RBC) transfusions. Based on long-standing assumptions, each RBC unit is thought to increase recipient hemoglobin by 1 g/dL, but smaller increments can occur. A better understanding of recipient factors affecting hemoglobin increments could help providers manage these patients.Methods: Data were collected as a part of the observational Red Cells in Outpatients Transfusion Outcomes (RETRO) study of outpatients with hematologic or cancer-related diagnoses. Hemoglobin was measured before transfusion and 30 minutes after transfusion. A classification and regression tree (CART) analysis was performed to identify statistically significant associations with clinical variables. A corresponding prediction equation was developed and validated using linear regression.Results: A total of 195 participants had both pre- and posttransfusion hemoglobin values for analysis. The median age was 66 years, and patients received one (73%) or two (27%) RBC units during the transfusion episode. The overall median change in hemoglobin was 0.6 g/dL per RBC unit. Both CART analysis and linear regression identified the following significant predictors of hemoglobin increment: number of units received (positive correlation), patient estimated circulating blood volume (negative correlation), pretransfusion hemoglobin (negative correlation), and patient age (negative correlation).Conclusion: In this study of outpatients with hematologic disease, most patients had a hemoglobin increment of less than 1 g/dL/unit. Recipient-specific factors influenced the hemoglobin increment at 30 minutes, and providers should consider circulating blood volume, pretransfusion hemoglobin, and recipient age, when developing patient-specific RBC transfusion plans for this unique cohort. [ABSTRACT FROM AUTHOR]

Background: Apheresis red blood cell (RBC) exchange (RCE) is a standard intervention for patients with sickle cell anemia (SCA) who have had previous thromboembolic stroke or intractable chronic pain. Replacing sickling cells with those containing hemoglobin A (HbA) minimizes microvascular pathophysiology that produces clinical crises. Limited data exist regarding the interval changes in HbA between transfusions. We sought to describe the HbA decrement between RCE procedures and its relationship to clinical status.Study Design and Methods: SCA patients (all hemoglobin SS disease) treated with maintenance RCE (n = 21) over a 15-month period at two neighboring institutions were retrospectively reviewed. Time-normalized daily HbA decrement was calculated to reflect loss of transfused RBCs, and annual events of either emergency department or hospital admissions for SCA complications were noted. Associations between HbA decrement and laboratory measures were calculated using mixed linear regression models and unpaired t test was used to compare HbA decrement between high and low event rate groups.Results: A total of 31 events were recorded, and mean HbA decrement per day was 0.77 ± 0.16%. The mean interval between RCEs was 36 ± 12 days. Patients with more annual events exhibited a significantly greater daily HbA decrement (p = 0.007). No significant association between RBC unit age and HbA decrement or annual event rate was observed.Conclusions: Patients exhibiting greater daily HbA decrement were more likely to have multiple emergency department visits or admissions for sickling crises. Modulating HbA decrement may merit study as an intermediate metric for interventions to improve outcomes in hemoglobin SS disease. [ABSTRACT FROM AUTHOR]

Background: American Association of Blood Banks (AABB) guidelines suggest that packed red blood cells (PRBCs) be administered through a dedicated intravenous (IV) catheter. Literature supporting this broad-scope declaration are scarce. Obtaining additional IV access is painful, costly, and an infectious risk. We evaluated the effect of co-incubating PRBCs with crystalloids and medications on PRBC hemolysis, membrane deformability, and aggregation, as well as medication concentration.Methods: PRBCs were co-incubated 5 minutes with plasma, normal saline (NS), 5% dextrose in water (D5W), Plasmalyte, epinephrine (epi), norepinephrine (norepi), dopamine (dopa), or Propofol (prop). Samples were then assessed for hemolysis (free hemoglobin, serum potassium), membrane deformability (elongation index [EI]), aggregation (smear, critical shear stress [mPa]) and drug concentration (High Performance Liquid Chromatography/Tandem Mass Spectrometry [LCMS-MS]). Significance (p ≤ 0.05) was determined by Wilcoxon-paired comparisons or Wilcoxon/Kruskall Willis with post-hoc Dunn's test.Results: Compared to co-incubation with plasma: 1) co-incubation resulted in significantly increased hemolysis only when D5W as used (free hemoglobin, increased potassium); 2) EI trended lower when co-incubated with D5W and trended toward higher when co-incubated with prop; 3) aggregation was significantly lower when PRBCs co-incubated with NS, D5W, or Plasmalyte, and trended lower when co-incubated with epi, norepi, or dopa. Medication concentrations were between those predicted by distribution only in plasma and distribution through the entire intra- and extracellular space.Conclusion: Our data suggest that 5 minutes of PRBC incubation with isotonic crystalloids or catecholamines does not deleteriously alter PRBC hemolysis, membrane deformability, or aggregation. Co-incubation with D5W likely increases hemolysis. Propofol may promote hemolysis. [ABSTRACT FROM AUTHOR]

Background: Although females have a lower baseline hemoglobin (Hb) compared to males, it is unknown whether females have a greater tolerance for anemia when hospitalized. We tested the hypothesis that females tolerate severe anemia better than males, with decreased inpatient mortality in this setting.Study Design and Methods: We conducted a retrospective cohort study in 230,644 adult patients admitted to Johns Hopkins Hospital from January 2009 to June 2016. The relationships between nadir Hb and percentage change in Hb with inpatient mortality were assessed for nontransfused males and females. A multivariable logistic regression was used to determine risk-adjusted differences between males and females for the likelihood of inpatient mortality at nadir Hb levels of 5, 6, and 7 g/dL.Results: Males had increased mortality when nadir Hb was 6.0 g/dL or less (p < 0.05), whereas females did not. The risk-adjusted likelihood for inpatient mortality was greater for males compared to females at a nadir Hb of 6 g/dL or less (odds ratio, 1.84; 95% confidence interval, 1.09-3.16) (p = 0.02), but this sex-related difference was not significant at a nadir Hb of 5 or 7 g/dL or less. Inpatient mortality increased significantly in both males and females when the percentage decrease in Hb was greater than 50% from baseline (p < 0.05).Conclusions: Compared to males, females tolerate a lower nadir Hb, but a similar percentage change in Hb, before an increase in inpatient mortality is recognized. The findings suggest that females may be "preconditioned" to tolerate anemia better than males. [ABSTRACT FROM AUTHOR]

Background: Blood bank inventories must balance adequate supply with minimal outdate rates. The day-to-day practice of ordering red blood cell (RBC) inventory usually involves manually comparing current inventory levels with predetermined thresholds calculated from historical usage and ordering the difference. To date, there have been no published methods for ordering RBC inventory based on laboratory characteristics of admitted patients.Study Design and Methods: We designed and implemented a blood ordering algorithm to provide a more accurate measure of predicted RBC utilization in our institution. Cerner Command Language (Cerner Millennium) was used to extract and combine historical RBC unit usage, current inventory levels, and system-wide hematology values and blood groups. This report contains a suggested order based on current inventory, historical inventory data, ABO group, and the current "anemia index" for the institution.Results: The mean daily total RBC inventory was significantly reduced after implementation (401.7 units vs. 309.0 units, p < 0.05). There was a significant reduction in monthly RBC outdates in this period (19.1 vs. 8.1, p < 0.05). The age of RBCs at time of transfusion was reduced as well.Conclusion: We developed a novel algorithm that automatically generates a suggested RBC inventory order using real-time hospital-wide survey of patient ABO typing, hematology values, and historical data. After implementation of the algorithm we demonstrated a significant reduction in daily inventory levels and RBC outdate rates. [ABSTRACT FROM AUTHOR]

Background: RBC concentrates are commonly stored for up to 42 days but there has been conflicting evidence on the effect of storage duration and clinical outcomes. Most clinical studies have focused on possible associations between duration of storage time and risk for adverse outcomes, including mortality. Recent clinical trials did not find any such associations, but fewer studies have addressed whether storage time affects component efficacy. The main aim of this study was to determine the effect of RBC storage time on hemoglobin increment in transfused patients.Study Design and Methods: Transfusion data on a cohort of patients with myelodysplastic syndromes were linked to hemoglobin measurements taken between 2 days before and 28 days after a transfusion episode. We applied a mixed-effect linear regression model, accounting for patient characteristics and time from transfusion to next hemoglobin measurement, to study the effect of RBC storage on the hemoglobin increment.Results: The study population consisted of 225 patients who received 6437 RBC units. Compared to units stored less than 5 days, transfusion of blood units stored 5 to 9, 10 to 19, 20 to 29, or 30 or more days resulted in hemoglobin increases that were 0.83 (95% confidence interval [CI], 0.24-1.41), 0.92 (95% CI, 0.34-1.51), 1.33 (95% CI, 0.65-2.02) and 1.51 (95% CI, 0.58-2.43) g/L lower, respectively, per RBC unit. Results were consistent in sensitivity analyses.Conclusions: Longer RBC storage was associated with a smaller increase in hemoglobin concentration after transfusion. Although statistically significant, the effect was modest, and its clinical relevance in subgroups of patients should be investigated in prospective clinical trials. [ABSTRACT FROM AUTHOR]

Background: To reduce donor iron deficiency in whole blood donors, we changed our hemoglobin (Hb) cutoff in males and interdonation interval in females.Study Design and Methods: A change in messaging to females in fall 2016 was followed by changing the interdonation interval from 56 to 84 days in the appointment booking system (December 2016) and actual donation criterion (March 2017). The minimum Hb for males increased from 125 g/L to 130 g/L (March 2017). We evaluated Hb levels and deferral rates, donor presentations with a Hb level below 120 g/L, donation frequency, and donor base size before and after these changes.Results: The Hb deferral rate decreased in females from 13.0% to 9.5%, increased in males from 1.2% to 2.1%, and decreased overall from 6.8% to 5.4% (all p < 0.001). Mean Hb increased from 135.0 g/L to 136.2 g/L in females and from 149.9 g/L to 150.6 g/L in males (both p < 0.0001). The percentage of presentations with Hb below 120 g/L decreased by 27% in males and females (p < 0.001). Annual donation frequency decreased by 12% in females and 4% in males; the donor base was expanded by 5.8%.Conclusions: Many positive impacts were seen for female donors, including a shift in the Hb distribution curve to the right, and a large reduction in Hb deferrals. For males, there was an increase in Hb deferrals and a small increase in mean Hb. Changes were related to both reduced donation frequency and a shift in composition of the donor base. [ABSTRACT FROM AUTHOR]

Background: Blood donors have an increased risk of low hemoglobin (Hb) levels due to iron deficiency. Therefore, knowledge of genetic variants associated with low Hb could facilitate individualized donation intervals. We have previously reported three specific single-nucleotide polymorphisms that were associated with ferritin levels in blood donors. In this study, we investigated the effect of these single-nucleotide polymorphisms on Hb levels in 15,567 Danish blood donors.Study Design and Methods: We studied 15,567 participants in the Danish Blood Donor Study. The examined genes and single-nucleotide polymorphisms were 1) TMPRSS6, involved in regulation of hepcidin: rs855791; 2) HFE, associated with hemochromatosis: rs1800562 and rs1799945; 3) BTBD9, associated with restless leg syndrome: rs9357271; and 4) TF, encoding transferrin: rs2280673 and rs1830084. Associations with Hb levels and risk of Hb deferral were assessed in multivariable linear and logistic regression models.Results: The HFE,rs1800562 G-allele and the HFE rs1799945 C-allele were associated with lower Hb levels in men and women, and with an increased risk of Hb below 7.8 mmol/L (12.5 g/dL) in women. Only the rs1799945 C-allele increased the risk of Hb below 8.4 mmol/L (13.5 g/dL) in men. In TMPRSS6, the rs855791 T-allele was associated with lower Hb levels in both men and women, and with an increased risk of low Hb among women.Conclusion: With this study we demonstrate that HFE and TMPRSS6 are associated with Hb levels and risk of Hb below the limit of deferral. Thus, genetic testing may be useful in a future assay for personalized donation intervals. [ABSTRACT FROM AUTHOR]

Background: Several studies in developed countries have demonstrated high levels of iron deficiency (ID) among blood donors. There is a paucity of data for developing countries where blood shortages remain a major concern.Study Design and Methods: A total of 4412 donors were enrolled in the study. Specimens were collected for full blood count, iron, transferrin saturation, and ferritin assessment. Donor demographics were recorded. ID was indicated by a ferritin level of less than 20 ng/mL for men and less than 12 ng/mL for women. Anemia was defined as hemoglobin levels less than 12.5 g/dL. Regression models for predictors of ID were developed.Results: A total of 17.5% of all donors had ID, with 16.3% prevalence in women and 18.6% in men. Low hemoglobin had the highest association with ID (adjusted odds ratio [AOR], 11.078; 95% confidence interval [CI], 7.915-15.505); male donors had twice the odds of ID compared to female donors (AOR, 2.501; 95% CI, 1.964-3.185), while increasing age was associated with lower odds (AOD, 0.965; 95% CI, 0.956-0.975). Among male donors, an interdonation interval of less than 3 months (AOR, 2.679; 95% CI, 1.929-3.720) was associated with ID. Compared to other females combined, colored female donors (AOR, 2.335; 95% CI, 1.310-4.160) had higher odds and black female donors (AOR, 0.559; 95% CI, 0.369-0.845) lower odds of ID.Conclusion: ID is common among South African donors; low hemoglobin, gender, ethnicity, and past donation history is independently associated with ID. Recommendations aimed at protecting donor health may increase blood shortages in South Africa. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin-based oxygen carriers (HBOCs) are potential alternatives to red blood cells in transfusions. Clinical trials using early versions of HBOCs noted adverse effects that appeared to result from removal of the vasodilator nitric oxide (NO). Previous reports suggest that size-enlarged HBOCs may avoid NO-rich regions along the vasculature and therefore not cause vasoconstriction and hypertension.Study Design and Methods: Hemoglobin (Hb) bis-tetramers (bis-tetramers of hemoglobin that are prepared using CuAAC chemistry [BT-Hb] and bis-tetramers of hemoglobin that are specifically acetylated and prepared using CuAAC chemistry [BT-acHb]) can be reliably produced by a bio-orthogonal cyclo-addition approach. We considered that an HBOC derived from chemical coupling of two Hbs would be sufficiently large to avoid NO scavenging and related side effects. The ability of intravenously infused BT-Hb and BT-acHb to remain in the circulation without causing hypertension were determined in wild-type (WT) and diabetic (db/db) mouse models.Results: In WT mice, the coupled oxygen-carrying proteins retained their function over several hours after administration. No significant changes in systolic blood pressure from baseline were observed after intravenous infusion of BT-Hb or BT-acHb in awake WT and db/db mice. In contrast, infusion of native Hb or cross-linked Hb tetramers in both animal models induced systemic hypertension.Conclusion: The results of this study indicate that bis-tetrameric HBOCs derived from the bio-orthogonal cyclo-addition process are likely to overcome clinical issues that arise from NO scavenging by Hb derivatives. [ABSTRACT FROM AUTHOR]

BACKGROUND: ABO dependent variation in von Willebrand factor (vWF) and factor VIII have an impact on hemostasis. Several contradictory studies have investigated the influence of ABO blood type in surgical hemorrhage. Emergency surgery is associated with an increased risk of perioperative hemorrhage leading to inferior clinical outcomes. The aim of this study was to investigate if patients with blood type O received more transfusions with blood components compared with non‐O patients after major emergency abdominal surgery. STUDY DESIGN AND METHODS: This retrospective observational study combined perioperative data including hemoglobin with transfusion data in patients undergoing emergency surgery at a university hospital between January 2010 and October 2016. The primary outcome was postoperative transfusion stratified into early transfusion, within 24 hours after surgery, and late transfusion from 24 hours to 7 days (POD7) after surgery. RESULTS: A total of 869 patients were included, 363 patients with blood type O (42.0%) and 501 (58.0%) with blood type non‐O. We found no difference in the need for transfusion with 42 (11.6%) patients with blood type O and 66 (13.2%) patients with blood type non‐O receiving early transfusion and 39 (13.4%) and 48 (11.9%) of O and non‐O patients, respectively, receiving late transfusion. Multivariate logistic regression analysis showed an adjusted OR of 0.915 (95% CI 0.569–1.471) for early transfusion and an adjusted OR of 1.307 (95% CI 0.788–2.169) for late transfusion in patients with blood type O. Likewise, no difference was seen with respect to the change in hemoglobin levels before and after surgery as well as transfused volume. CONCLUSION: We did not find an association between transfusion or perioperative changes in hemoglobin with respect to blood type ABO. [ABSTRACT FROM AUTHOR]

BACKGROUND: Blood donors have an increased risk of low hemoglobin (Hb) levels due to iron deficiency. Therefore, knowledge of genetic variants associated with low Hb could facilitate individualized donation intervals. We have previously reported three specific single‐nucleotide polymorphisms that were associated with ferritin levels in blood donors. In this study, we investigated the effect of these single‐nucleotide polymorphisms on Hb levels in 15,567 Danish blood donors. STUDY DESIGN AND METHODS: We studied 15,567 participants in the Danish Blood Donor Study. The examined genes and single‐nucleotide polymorphisms were 1) TMPRSS6, involved in regulation of hepcidin: rs855791; 2) HFE, associated with hemochromatosis: rs1800562 and rs1799945; 3) BTBD9, associated with restless leg syndrome: rs9357271; and 4) TF, encoding transferrin: rs2280673 and rs1830084. Associations with Hb levels and risk of Hb deferral were assessed in multivariable linear and logistic regression models. RESULTS: The HFE,rs1800562 G‐allele and the HFE rs1799945 C‐allele were associated with lower Hb levels in men and women, and with an increased risk of Hb below 7.8 mmol/L (12.5 g/dL) in women. Only the rs1799945 C‐allele increased the risk of Hb below 8.4 mmol/L (13.5 g/dL) in men. In TMPRSS6, the rs855791 T‐allele was associated with lower Hb levels in both men and women, and with an increased risk of low Hb among women. CONCLUSION: With this study we demonstrate that HFE and TMPRSS6 are associated with Hb levels and risk of Hb below the limit of deferral. Thus, genetic testing may be useful in a future assay for personalized donation intervals. [ABSTRACT FROM AUTHOR]