Donor Evaluation Study-III Research Articles

Bleeding recurrence risk among hospitalized patients undergoing therapeutic plasma exchange: a multi-center study.

In hospitalized patients undergoing therapeutic plasma exchange (TPE), it is not known how TPE-associated bleeding risk is impacted by a prior bleeding episode. Therefore, to assess the prevalence and predictors of bleeding recurrence, we analyzed data from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). Using a retrospective cross-sectional analysis of REDS-III public use files, we identified hospitalized adults who had a major bleeding episode prior to their first TPE procedure. Patients were classified into two cohorts based on bleeding recurrence (no-recurrence vs recurrence). After identifying potential predictors, we used multiple imputation by chained equations to impute variables with <30% missing data. Variable selection was optimized using a 10-fold cross validated least absolute shrinkage and selection operator. Final predictors were identified by fitting a logistic regression model. In 310 patients with major bleeding prior to TPE initiation, bleeding recurred in 121 (39.0%). We identified the following seven unique predictors: 1) >10 TPE procedures (OR 2.23); 2) intensive care unit stay (OR 1.35); 3) thrombocytopenia (OR 1.26); 4) surgery (OR 1.22); 5) hepatic disease (OR 1.21); 6) 6-10 TPE procedures (OR 1.04); and 7) Asian race (OR 1.01). We also identified the following five interactions: 1) surgery and therapeutic anticoagulation (OR 1.50); 2) 6-10 TPE procedures and therapeutic anticoagulation (OR 1.05); 3) 6-10 TPE procedures and antiplatelets (OR 1.02); 4) >10 TPE procedures and antiplatelets (OR 1.00); and 5) albumin-only TPE and antiplatelets (OR 0.53). When assessed for adjusted performance, the prediction model had a C-statistic of 0.617 (95% CI 0.613-0.619) and Brier Score of 0.342 (95% CI 0.340-0.347). In this study assessing predictors of bleeding recurrence among hospitalized patients undergoing TPE, we identified seven variables and five interactions. These findings should be validated in future studies.

In hospitalized patients undergoing therapeutic plasma exchange, major bleeding prevalence depends on the bleeding definition: An analysis of The Recipient Epidemiology and Donor Evaluation Study-III.

Major bleeding in patients undergoing therapeutic plasma exchange (TPE) has been studied in large databases; but without standardizing bleeding definitions. Therefore, we used standardized definitions to evaluate major bleeding in hospitalized patients undergoing TPE using public use data files from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). In a retrospective cross-sectional analysis, we identified TPE-treated adults in a first inpatient encounter. We evaluated major bleeding prevalence using (1) International Classification of Diseases (ICD) or Current Procedural Terminology (CPT) codes, (2) packed red blood cell (PRBC) transfusion, or (3) hemoglobin (Hgb) decline. Patients with major bleeding prior to their first TPE were excluded from the analysis. Among 779 patients undergoing TPE, major bleeding by at least one of the three bleeding definitions occurred in 135 patients (17.3%). For each of the ICD/CPT, PRBC, and Hgb definitions, the prevalence of major bleeding was 2.8% (n = 31), 7.4% (n = 81), and 5.4% (n = 59), respectively. Only 3.7% of bleeds (5/135) were captured by all three definitions and 19.3% (26/135) exclusively by any two pairwise definitions. The addition of PRBC transfusion and Hgb decline to ICD/CPT code definitions increased bleeding prevalence threefold. Among hospitalized adults undergoing TPE in the REDS-III study, the prevalence of major bleeding was 17.3%. The addition of PRBC and Hgb decline to ICD codes increased bleeding prevalence threefold. Future studies are needed to develop validated models that identify patients at risk for major bleeding during TPE.

Associations of donor, component, and recipient factors on hemoglobin increments following red blood cell transfusion in very low birth weight infants.

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. 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. 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. 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.

Blood donor, component, and recipient-specific factors associated with venous thromboembolism in transfused hospitalized adult patients: Data from the recipient epidemiology and donor evaluation Study-III (REDS-III).

Growing evidence suggests multiple pathophysiological mechanisms linking red blood cells (RBC) transfusions to thrombosis. This study examined blood donor, component, and recipient factors which may be associated with thromboembolic outcomes following RBC transfusion. We utilized the Recipient Epidemiology Donor Evaluation Study-III (REDS-III) database on patients transfused in 12 hospitals between 2013-2016. Stratified Cox proportional hazards regression models with time-dependent exposures were used to examine associations of donor and component modification characteristics on venous thromboembolism (VTE) in patients transfused RBC units. 59,603 patients were transfused 229,500 RBC units during 79,298 hospitalizations with post-transfusion VTE occurring in 1869 (2.4%) of patients. In adjusted regression analyses, a per RBC-unit risk of VTE was present for gamma irradiation (HR=1.03; 95% CI: 1.02-1.03), female donor sex (HR=1.01; 95% CI: 1.00-1.01), storage duration greater than 5 weeks (HR=1.01; 95% CI: 1.01-1.02), AS-1 storage solution (HR=1.01; 95% CI: 1.00-1.01), and apheresis-derived collections (HR=1.01; 95% CI: 1.01-1.02). Among recipient factors, male sex (HR=1.03; 95% CI: 1.02-1.04), pre-transfusion hemoglobin level (HR=0.94; 95% CI: 0.94-0.94), body mass index strata (HR=1.11; 95% CI: 1.08-1.14), and principal diagnoses including malignancy (HR=1.13; 95% CI: 1.10-1.16), cardiac arrest (HR=1.38; 95% CI:1.07-1.77) and hip fracture (HR=1.59; 95% CI:1.53-1.66) were associated with VTE in adjusted analyses. We identified several donor, component, and recipient-specific factors associated with VTE in transfused hospitalized adult patients. In adjusted models, the dose-dependent associations of donor and component-specific factors with VTE were modest and unlikely to be clinically significant in the majority of transfused patients. Additional mechanistic and clinical studies linking blood donor and component factors with thrombotic outcomes are needed.

CLINICAL AND GENETIC FACTORS ASSOCIATED WITH OSTEONECROSIS IN BRAZILIAN SICKLE CELL DISEASE PATIENTS: CASE-CONTROL STUDY

Sickle cell disease (SCD) includes a group of hereditary disorders characterized by mutations on the gene that codes hemoglobin (Hb). Patients with SCD are vulnerable to vascular occlusion within bone tissue, which may result in complications such as medullary infarction in the diaphysis and osteonecrosis (ON), which affects the epiphysis. Both processes may result in substantial morbidity and pain for the patients. This study aims to identify factors associated with the development of ON in patients with SCD. A nested case-control study of patients with SCD from six Brazilian blood centers, participating in the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) Brazil SCD Cohort was performed. A history of ON was abstracted from participants medical record using standardized definitions to define cases. Cases were matched to controls without ON in a 1:3 ratio matched by age, genotype and blood center using propensity score. A genome-wide association study (GWAS) was conducted to identify single nucleotide polymorphisms (SNPs) associated with ON. There were 307 ON cases in the 2793 cohort participants (prevalence 11%) who were compared to 921 controls without ON. The most common locations of ON were the proximal femur (91.2%) and proximal humerus (7.7%). Variables independently associated with ON in a multivariable model included patients with more severe sickle cell disease (SS, Sβ0, severe Sβ+ or SD genotypes, OR 1.81, 95% CI 1.11; 2.95 compared to less severe genotypes SC/SB+), higher values of hemoglobin (OR 1.25, 1.12; 1.39), hospitalization by pain crisis (OR 1.44, 1.06; 1.94), chronic transfusion treatment (OR 1.53, 1.10; 2.11), acute chest syndrome (OR 1.46, 1.06; 2.00), sepsis/bacteremia (OR 1.67, 1.03; 2.70) and osteomyelitis (OR 1.72, 1.05; 2.80). Increased indirect bilirubin and stroke were associated with a lower chance of developing ON (OR 0.81, 0.71; 0.93 for indirect bilirubin and OR 0.42, 0.24; 0.72 for stroke). The GWAS suggested an association of ON with the gene doublesex and mab-3 related transcription factor 2 (DMRT2) (p < 5 × 10−8). SCD is the most common monogenic disorder in Brazil and is associated with multisystem complications. Orthopedic complications represent 31.0% of these manifestations, with ON being the most common non-infectious joint complication. Knowing the risk factors that precede ON may help to diagnose and treat it early in order to improve the quality of life of patients. The few studies carried out in the Brazilian population on the occurrence of ON in SCD patients had small sample sizes. A higher chance of having ON was associated with patients with higher hemoglobin levels, more hospitalizations for pain crises and acute chest syndrome. Also the relationship of treatment with chronic transfusion, sepsis/bacteremia and osteomyelitis were associated with ON, which may indicate that the occurrence of this complication may be multifactorial or related to the severity of SCD. SNPs near DMRT2, a gene previously associated with skeletal disorders, rib malformation in a newborn and transition of endochondral bone formation, showed an altered risk for ON.

CLINICAL PREDICTORS OF VASO-OCCLUSIVE PAIN HOSPITALIZATION IN PATIENTS WITH SICKLE CELL DISEASE (SCD)

Vaso-occlusive painful episodes (VOE) are the most common clinical manifestation of sickle cell disease (SCD) and the primary reason for hospitalizations and emergency visits. This project aims to identify the clinical predictors of VOE hospitalization in adult participants of the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) Brazil SCD Cohort. The REDS-III Brazil SCD Cohort enrolled participants from 2013 to 2015 who were followed until 2018. Participants were randomly selected as eligible from public blood centers in 6 cities. Medical records were reviewed to abstract clinical data including the indications for all hospitalizations that occurred from one year prior to enrollment through the end of follow up. Adult cohort participants with 3+ hospitalizations per year due to VOE (cases) were compared to controls with less frequent VOE admissions to identify predictors of frequent VOE. Of the 2793 participants enrolled in the cohort, 184 (6.7%) had 3+ VOE admissions per year (5.5% of 1330 children <18yr and 7.5% of 1453 adults). Compared to adults with <3 VOE admissions/ year, the adults with frequent VOE had higher white blood cell counts (11,566 vs. 98,659 cells/uL), platelet counts (389,500 vs 357,333 cells/uL) and lower hemoglobinF (4.4% vs 6.9%) and were more likely to have received red blood cell transfusions (80% vs. 41%) and hydroxyurea (60% vs. 49%) in the past year. Acute chest syndrome, bacteremia, and asthma were also more common in adult cases compared to controls (83% vs 61%, 16% vs 8% and 17% vs 8%, respectively). Independent predictors of 3+ VOE admissions/year in multivariable models included higher white blood cell (OR 1 [1.000-1.001], history of acute chest syndrome (OR 2.8 [1.581-5.202] and treatment with hydroxyurea (OR 1.8 [1.123-3.038]. Frequent hospitalizations due to VOE are a marker of severe SCD used to identify patients for disease modifying therapy or even curative therapies such as bone marrow transplant. Understanding the significant predictors of frequent VOE in adults may identify other surrogate markers of severe disease that can be used to target therapies for high risk individuals. In this multi institutional cohort of SCD, white blood cell count and a history of acute chest syndrome were identified as significant independent predictors of frequent VOE while the association of hydroxyurea likely reflects treatment with this disease modifying therapy for frequent pain. Individuals with high white blood cell counts and acute chest syndrome should have close follow up to be monitored frequently and considered for early and aggressive treatment of pain as well as other disease modifying therapies.

Is Severity Score Associated With Indication for Hematopoietic Stem Cell Transplantation in Individuals With Sickle Cell Anemia?

Manifestations of sickle cell disease (SCD) begin early in childhood and cause morbidity and decreased life expectancy. Hematopoietic stem cell transplantation (HSCT) is curative but associated with risk of mortality attributable to the transplant. This risk should be counterbalanced with SCD morbidity and mortality. A severity score using a Bayesian network model was previously validated to predict the risk of death in adult individuals with SCD. The objective of this study is to calculate the severity scores of participants in a multicenter cohort of Brazilians with SCD, using a previously published Bayesian network-derived score, associated with risk of death and then compare the severity scores between participants with and without an indication for HSCT as defined by the Brazilian Ministry of Health (MoH) criteria. This is an observational, retrospective study. We analyzed 2063 individuals with sickle cell anemia from the Recipient Epidemiology and Donor Evaluation Study-III Brazil SCD cohort and applied a Bayesian network-derived score to compare candidates and non-candidates for HSCT according to the Brazilian MoH transplant criteria. Classical statistical methods were used to analyze data and make comparisons. We compared severity scores between cohort members with (n=431) and without (n=1632) HSCT indications according to Brazilian MoH. Scores were not different in adult participants with ≥1 HSCT indication when compared to those with no indication (mean 0.342 versus 0.292; median 0.194 versus 0.183, P=.354) and receiver operating characteristic curves did not demonstrate an obvious threshold to differentiate participants with or without HSCT indications. Severity score may predict risk of death but does not differentiate HSCT candidates. Current indications should be evaluated to ensure that patients with more severe disease who might benefit from HSCT are appropriately identified.

Transfusion practices for pediatric oncology and hematopoietic stem cell transplantation patients: Data from the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III)

To evaluate transfusion practices in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients. This is a multicenter retrospective study of children with oncologic diagnoses treated from 2013 to 2016 at hospitals participating in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III. Transfusion practices were evaluated by diagnosis codes and pre-transfusion laboratory values. A total of 4766 inpatient encounters of oncology and HSCT patients were evaluated, with 39.3% (95% confidence interval [CI]: 37.9%-40.7%) involving a transfusion. Red blood cells (RBCs) were the most commonly transfused component (32.4%; 95% CI: 31.1%-33.8%), followed by platelets (22.7%; 95% CI: 21.5%-23.9%). Patients in the 1 to <6 years of range were most likely to be transfused and HSCT, acute myeloid leukemia, and aplastic anemia were the diagnoses most often associated with transfusion. The median hemoglobin (Hb) prior to RBC transfusion was 7.5g/dl (10-90th percentile: 6.4-8.8g/dl), with 45.7% of transfusions being given at 7 to <8g/dl. The median platelet count prior to platelet transfusion was 20 × 109 /L (10-90th percentile: 8-51 × 109 /L), and 37.9% of transfusions were given at platelet count of >20-50 × 109 /L. The median international normalized ratio (INR) prior to plasma transfusion was 1.7 (10-90th percentile: 1.3-2.7), and 36.3% of plasma transfusions were given at an INR between 1.4 and 1.7. Transfusion of blood components is common in hospitalized pediatric oncology/HSCT patients. Relatively high pre-transfusion Hb and platelet values and relatively low INR values prior to transfusion across the studied diagnoses highlight the need for additional studies in this population.

Transfusion Practices in Pediatric Cardiac Surgery Requiring Cardiopulmonary Bypass: A Secondary Analysis of a Clinical Database.

To describe blood component usage in transfused children with congenital heart disease undergoing cardiopulmonary bypass surgery across perioperative settings and diagnostic categories. Datasets from U.S. hospitals participating in the National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III were analyzed. Inpatient admissions from three U.S. hospitals from 2013 to 2016. Transfused children with congenital heart disease undergoing single ventricular, biventricular surgery, extracorporeal membrane oxygenation. None. Eight hundred eighty-two transfused patients were included. Most of the 185 children with single ventricular surgery received multiple blood products: 81% RBCs, 79% platelets, 86% plasma, and 56% cryoprecipitate. In the 678 patients undergoing biventricular surgery, 85% were transfused plasma, 75% platelets, 74% RBCs, and 48% cryoprecipitate. All 19 patients on extracorporeal membrane oxygenation were transfused RBCs, plasma, and cryoprecipitate, and 18 were transfused platelets. Intraoperatively, patients commonly received all three components, while postoperative transfusions were predominantly single blood components. Pretransfusion hemoglobin values were normal/low-normal for age for all phases of care for single ventricular surgery (median hemoglobin 13.2-13.5 g/dL). Pretransfusion hemoglobin values for biventricular surgeries were higher intraoperatively compared with other timing (12.2 g/dL vs 11.2 preoperative and postoperative; p < 0.0001). Plasma transfusions for all patients were associated with a near normal international normalized ratio: single ventricular surgeries median international normalized ratio was 1.3 postoperative versus 1.8 intraoperative and biventricular surgeries median international normalized ratio was 1.1 intraoperative versus 1.7 postoperative. Intraoperative platelet transfusions with biventricular surgeries had higher median platelet count compared with postoperative pretransfusion platelet count (244 × 109/L intraoperative vs 69 × 109/L postoperative). Children with congenital heart disease undergoing cardiopulmonary bypass surgery are transfused many blood components both intraoperatively and postoperatively. Multiple blood components are transfused intraoperatively at seemingly normal/low-normal pretransfusion values. Pediatric evidence guiding blood component transfusion in this population at high risk of bleeding and with limited physiologic reserve is needed to advance safe and effective blood conservation practices.

Red Blood Transfusion Does Not Increase Risk for Venous or Arterial Thrombosis

▪Introduction: Previous observational studies in patients with cancer, subarachnoid hemorrhage, or undergoing surgery suggested an association between red blood cell (RBC) transfusion and an increased risk for arterial and venous thrombosis, findings warranting further evaluation.Methods: The risk of thrombosis in all hospitalized patients was assessed in patients admitted to 12 hospitals located across the United States in New Haven, Pittsburgh, Milwaukee, and San Francisco using the Recipient Database from the NHLBI Recipient Epidemiology and Donor Evaluation Study-III. All patients admitted between January 2013 and September 2015 were included in analyses. A thrombosis event was defined as an admission with an ICD-9 code of arterial or venous thrombosis as a primary or secondary diagnosis and administration of a therapeutic dose of an anticoagulant or antiplatelet agent during that admission. The timing of the thrombosis was based upon medication administration time. Timing of transfusion was based upon release of RBC from the blood bank. Patients using anticoagulant medications at home or with a history of thrombosis diagnostic code were excluded. Encounters with a thrombotic event within the first 24 hours after admission were also excluded as thrombosis was likely the etiology of the admission. A proportional hazards regression model was used to evaluate the effect of transfusion on the risk of thrombosis with transfusion treated as a time-varying predictor. Discharge without thrombosis, in-hospital thrombosis and death were considered competing risks. Estimates were adjusted for age, sex, hospital, medical comorbidities, and surgical procedures.Results: Of 657,412 inpatient admissions, 67,176 (10.2%) received at least one RBC transfusion; median age was 58 and 53.6% were women. Two percent (12,927) of patients experienced a thrombosis. Of these, 2,587 developed thrombosis after a RBC transfusion. In a univariable analysis, many surgical procedures were associated with a risk of thrombosis including cardiac surgery [Hazard Ratio (HR)=3.25 (3.05-3.47)] and vascular surgery, HR=1.90 (1.82-1.99). Comorbidities were also associated with thrombosis including heart arrhythmias HR=1.60 (1.54-1.66), hypertension HR=1.31 (1.26-1.37), anemia HR=1.32 (1.17-1.49), and metastatic cancer HR=1.36 (1.28-1.45). In unadjusted analyses, RBC transfusion was associated with an increased risk of thrombosis [HR=1.3 (95% CI 1.25-1.36)] (Table 1). The risk of thrombosis increased with the number of RBC units transfused. However, after adjustment for surgical procedures, age, sex, hospital, and comorbidities, no effect of RBC transfusion on risk of thrombosis was found [HR 0.98 (95% CI: 0.94-1.03)] (Table 1).Conclusions: In univariate analyses there are multiple risks for venous and arterial thrombosis, including many surgical procedures and medical comorbidities, as well as RBC transfusion. However, after adjustment for these multiple risk factors, RBC transfusion was not associated with a risk for arterial or venous thrombosis. Thus, this study of all patients admitted to 12 hospitals in the US did not identify RBC transfusion as an independent risk factor for thrombosis. The REDS-III database contains detailed information about comorbidities, medications, and timing of transfusion which allowed us to carefully define a thrombotic episode and its temporal relationship to RBC transfusion, and adjust for confounders that may not have been available in other datasets. Our findings do not rule out the possibility of a patient subset where RBC transfusion increases risk for thrombosis, such as patients with an underlying genetic hypercoagulable risk, but they do indicate that RBC transfusion does not appear to be an important risk factor for thrombosis in most patients. As such, receiving a blood transfusion should not influence decisions about venous thrombosis prophylaxis in hospitalized patients. [Display omitted] DisclosuresMast:Novo Nordisk: Research Funding.

Transfusion practices in a large cohort of hospitalized children.

While previous studies have described the use of blood components in subsets of children, such as the critically ill, little is known about transfusion practices in hospitalized children across all departments and diagnostic categories. We sought to describe the utilization of red blood cell, platelet, plasma, and cryoprecipitate transfusions across hospital settings and diagnostic categories in a large cohort of hospitalized children. The public datasets from 11 US academic and community hospitals that participated in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) were accessed. All nonbirth inpatient encounters of children 0-18 years of age from 2013 to 2016 were included. 61,770 inpatient encounters from 41,943 unique patients were analyzed. Nine percent of encounters involved the transfusion of at least one blood component. RBC transfusions were most common (7.5%), followed by platelets (3.9%), plasma (2.5%), and cryoprecipitate (0.9%). Children undergoing cardiopulmonary bypass were most likely to be transfused. For the entire cohort, the median (interquartile range) pretransfusion laboratory values were as follows: hemoglobin, 7.9 g/dl (7.1-10.4 g/dl); platelet count, 27 × 109 cells/L (14-54 × 109 cells/L); and international normalized ratio was 1.6 (1.4-2.0). Recipient age differences were observed in the frequency of RBC irradiation (95% in infants, 67% in children, p < .001) and storage duration of RBC transfusions (median storage duration of 12 [8-17] days in infants and 20 [12-29] days in children, p < .001). Based on a cohort of patients from 2013 to 2016, the transfusion of blood components is relatively common in the care of hospitalized children. The frequency of transfusion across all pediatric hospital settings, especially in children undergoing cardiopulmonary bypass, highlights the opportunities for the development of institutional transfusion guidelines and patient blood management initiatives.

Variation in Neonatal Transfusion Practice

To estimate the incidence of blood product transfusion, including red blood cells, platelets, and plasma, and characterize pretransfusion hematologic values for infants during their initial hospitalization after birth. Retrospective cohort study using data from 7 geographically diverse US academic and community hospitals that participated in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) from 2013 to 2016. Pretransfusion hematologic values were evaluated closest to each transfusion and no more than 24hours beforehand. Data from 60 243 infants were evaluated. The incidence of any transfusion differed by gestational age (P<.0001), with 80% (95% CI 76%-84%) transfused at <27weeks of gestation (n=329) and 0.5% (95% CI 0.5%-0.6%) transfused at ≥37weeks of gestation (n=53 919). The median pretransfusion hemoglobin was 11.2g/dL (10th-90th percentile 8.8-14.1) for the entire cohort, ranging from 10.5g/dL (8.8-12.3) for infants born extremely preterm at <27weeks of gestation to 13.0g/dL (10.5-15.5) for infants born at term. The median pretransfusion platelet count (×109/L) was 71 (10th-90th percentile 26-135) for the entire cohort, and was >45 for all gestational age groups examined. The median pretransfusion international normalized ratio for the entire cohort was 1.7 (10th-90th percentile 1.2-2.8). There is wide variability in pretransfusion hemoglobin, platelet count, and international normalized ratio values for neonatal transfusions. Our findings suggest that a large proportion of neonatal transfusions in the US are administered at thresholds greater than supported by the best-available evidence and highlight an opportunity for improved patient blood management.

Red blood cell transfusion does not increase risk of venous or arterial thrombosis during hospitalization.

Previous observational studies suggest associations between red blood cell (RBC) transfusion and risk for arterial or venous thrombosis. We determined the association between thrombosis and RBC transfusion in hospitalized patients using the Recipient Database from the National Heart Lung and Blood Institute (NHLBI) Recipient Epidemiology and Donor Evaluation Study-III. A thrombotic event was a hospitalization with an arterial or venous thrombosis ICD-9 code and administration of a therapeutic anticoagulant or antiplatelet agent. Patients with history of thrombosis or a thrombosis within 24 hours of admission were excluded. A proportional hazards regression model with time-dependent covariates was calculated. Estimates were adjusted for age, sex, hospital, smoking, medical comorbidities, and surgical procedures. Of 657 412 inpatient admissions, 67 176 (10.2%) received at least one RBC transfusion. Two percent (12927) of patients experienced a thrombosis. Of these, 2587 developed thrombosis after RBC transfusion. In unadjusted analyses, RBC transfusion was associated with an increased thrombosis risk [HR = 1.3 (95% CI 1.23-1.36)]. After adjustment for surgical procedures, age, sex, hospital, and comorbidities, no association between RBC transfusion on risk of venous and arterial thrombosis was found [HR 1.0 (95% CI: 0.96-1.05)]. Thus, RBC transfusion does not appear to be an important risk factor for thrombosis in most hospitalized patients.

The evanescence and persistence of RBC alloantibodies in blood donors.

Blood donors represent a healthy population, whose red blood cell (RBC) alloantibody persistence or evanescence kinetics may differ from those of immunocompromised patients. A better understanding of the biologic factors impacting antibody persistence is warranted, as the presence of alloantibodies may impact donor health and the fate of the donated blood product. Donor/donation data collected from four US blood centers from 2012 to 2016 as part of the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) were analyzed. Clinically significant antibodies from blood donors with more than one donation who underwent at least one follow-up antibody screen after the initial antibody identification were included. Of 632,378 blood donors, 481 (128 males and 353 females) fit inclusion criteria. Antibody screens detected 562 alloantibodies, with 368 of 562 (65%) of antibodies being persistently detected and with 194 of 562 (35%) becoming evanescent. Factors associated with antibody persistence included antibody specificity, detection at the first donation, reported history of transfusion, and detection of multiple antibodies concurrently. Anti-D, C, and Fya were most likely to persist, while anti-M, Jka , and S were most frequently evanescent. These data provide insight into variables impacting the duration of antibody detection, and they may also influence blood donor center policies regarding donor recruitment/acceptance.

Association of donor age, body mass index, hemoglobin, and smoking status with in-hospital mortality and length of stay among red blood cell-transfused recipients.

Recent publications have reported conflicting findings regarding associations of blood donor demographics and mortality of transfused patients. We hypothesized that the analysis of additional donor characteristics and consideration of alternative outcomes might provide insight into these disparate results. We analyzed data from a retrospective cohort of transfused patients from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). We used stratified Cox regression models to estimate associations between blood donor characteristics and hospital mortality and posttransfusion length of stay among patients transfused red blood cell (RBC) units. Donor characteristics evaluated included age, body mass index, hemoglobin levels, and smoking status. The statistical analyses were adjusted for recipient factors, including total number of transfusions. We studied 93,726 patients in 130,381 hospitalizations during which 428,461 RBC units were transfused. There were no associations between blood donor characteristics and hospital mortality. Receipt of RBC units from donors less than 20 years of age was associated with a shorter hospital length of stay (hazard ratio for discharge per transfused unit, 1.03; 95% confidence interval, 1.02-1.04; p < 0.001) but not for other donor characteristics. We found no evidence of associations between blood donor factors and in-hospital mortality. Our finding of shorter hospital length of stay in patients transfused RBCs from younger donors is intriguing but requires confirmation. Future collaborations are needed to develop a framework of appropriate methodologic approaches to be used in linked analyses across large cohorts.

Association of Blood Donor Sex and Prior Pregnancy With Mortality Among Red Blood Cell Transfusion Recipients

Evidence regarding associations of blood donor sex with mortality among red blood cell transfusion recipients is conflicting. To study associations of donor sex and prior pregnancy with mortality of transfusion recipients. Data from 3 retrospective cohorts of transfusion recipients (the Kaiser Permanente Northern California [KPNC] and Recipient Epidemiology and Donor Evaluation Study-III [REDS-III] databases of data from January 2013 to December 2016 and the Scandinavian Donations and Transfusions [SCANDAT] database with data from January 2003 to December 2012) were analyzed. Final dates of follow-up were December 31, 2016, for the KPNC and REDS-III cohorts and December 31, 2012, for the SCANDAT cohort. Stratified Cox regression models were used to estimate associations between donor exposure groups with risk of mortality, adjusting for the number of red blood cell unit transfusions. The number of transfused red blood cell units from female donors, previously pregnant donors, and sex-discordant donors (male donor and female recipient or female donor and male recipient). In-hospital mortality. The study population included 34 662 patients (mean age, 69 years; 18 652 [54%] women) from the KPNC cohort, 93 724 patients (mean age, 61 years; 48 348 [52%] women) from the REDS-III cohort, and 918 996 patients (mean age, 72 years; 522 239 [57%] women) from the SCANDAT cohort. The median number of red blood cell transfusions per patient was 3 in the KPNC cohort, 2 in the REDS-III cohort, and 3 in the SCANDAT cohort. The percentage of transfusions from previously pregnant or parous donors was 9% in the KPNC cohort, 18% in the REDS-III cohort, and 25% in the SCANDAT cohort. The percentage of transfusions in the 3 cohorts from female donors ranged from 39% to 43%, from previously pregnant or parous donors ranged from 9% to 25%, and from sex-discordant donors ranged from 44% to 50%. There were 3217 in-hospital deaths in the KPNC cohort, 8519 in the REDS-III cohort, and 198 537 in the SCANDAT cohort. There were no statistically significant associations between any of the 3 donor exposures and in-hospital mortality in the 3 cohorts. Hazard ratios for in-hospital mortality per transfused unit from female donors were 0.99 (95% CI, 0.96-1.03) for the KPNC cohort, 1.00 (95% CI, 0.99-1.01) for the REDS-III cohort, and 1.00 (95% CI, 0.99-1.00) for the SCANDAT cohort. For units from previously pregnant or parous female donors, hazard ratios were 1.00 (95% CI, 1.00-1.01) for the KPNC cohort, 1.01 (95% CI, 0.98-1.03) for the REDS-III cohort, and 1.00 (95% CI, 1.00-1.01) for the SCANDAT cohort. For units from sex-discordant transfusions, hazard ratios were 1.02 (95% CI, 0.99-1.05) for the KPNC cohort, 0.99 (95% CI, 0.98-1.00) for the REDS-III cohort, and 1.00 (95% CI, 0.99-1.00) for the SCANDAT cohort. Among red blood cell transfusion recipients, transfusions from female, previously pregnant, or sex-discordant donors were not significantly associated with increased mortality.

Analysis of Clinical Blood Use in Emergency Blood Loss Patients

To explore the blood transfusion data of emergency hemorrhage patients, so as to provide the basis for improving the quality of emergency blood transfusion and guiding clinic rational blood transfusion. one thousand emergency blood loss patients once transfused RBC suspension were collected by Recipient Epidemiology and Donor Evaluation Study-III internationals Site range from November 2012 to November 2015. The clinical data including age, sex, clinical diagnosis etc were analyzed retrospectively. According to the quantity of blood transfusion the 1 000 patients were divided into 3 groups: low transfusion volume group(834),moderate transfusion volume group(116) and high transfusion volume group(50), difference was compared among the 3 groups，the transfusion predicting index and risk factor were analyzed by unvariate and multivoriate analyses using SPSS 23.0 software. High volume transfusion group was different from moderate and low volume transfusion in sex, pathogenesis, systolic pressure, hemoglobin level, with or without surgical operation, infusion volume of blood products, the retention time of ICU, total hospitalzed stay and mortality(P＜0.05), but there were no differences in age, respiration frequency, temperature before transfusion and creatinine level. The multivarate analysis showed that with or without surgical operation(OR=7.515，95% CI: 3.289-17.174, P=0.000), bleeding volume in surgery(OR=2.626, 95% CI: 1.428-4.828, P=0.043), the amount of transfused red blood cells(OR=2.574, 95% CI: 1.306-5.073, P=0.015), plasma transfusion or no(OR=2.118, 95% CI: 1.184-3.789, P=0.011), cryoprecipitate transfusion or no(OR=5.296, 95% CI: 2.164-12.960, P=0.000) were the independent risk factors for death resulted from emergency blood loss. The probability of massive transfusion in the trauma patients is higher，and the massive transfusion associates with increased mortality in the emergency blood loss patients. Surgery operation, bleeding volume in operation, amount of transfused red blood cells, plasma transfusion and cryoprecipitate transfusion may predict the mortality of patients with blood transfusion.

Prevalence and risk factors for RBC alloantibodies in blood donors in the Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III)

Little information exists on red blood cell (RBC) alloimmunization in healthy US blood donors, despite the potential significance for donors themselves, blood recipients, and the blood center. Donor/donation data were sourced from the Recipient Epidemiology and Donor Evaluation Study-III, which contains information from four US blood centers during 2012 through 2016. Multivariable logistic regression was used to assess prevalence of positive antibody screen by donor demographics, blood type, parity, and transfusion history. More than 2 million units were collected from 632,378 donors, with 0.51% of donations antibody screen positive and 0.77% of donors having at least one positive antibody screen. The most common antibody specificities were D (26.4%), E (23.8%), and K (21.6%). Regression analysis indicated that increasing age, female sex, D-negative status, and history of transfusion and pregnancy were positively associated with a positive antibody screen. Prior transfusion history was most strongly associated with a positive antibody screen, with donors reporting a prior transfusion having a higher adjusted odds ratio (3.9) of having a positive antibody screen compared to donors reporting prior pregnancy (adjusted odds ratio, 2.0). Though transfusion was a more potent immune stimulus for RBC alloantibody formation than pregnancy, the sheer number of previously pregnant donors contributed to pregnancy being a risk factor for the majority of clinically significant RBC alloantibodies detected in females. These findings on prevalence of and risk factors for RBC antibodies may have implications for future medical care of donors and for operations at blood centers.

Heterogeneity of blood processing and storage additives in different centers impacts stored red blood cell metabolism as much as storage time: lessons from REDS‐III—Omics

Biological and technical variability has been increasingly appreciated as a key factor impacting red blood cell (RBC) storability and, potentially, transfusion outcomes. Here, we performed metabolomics analyses to investigate the impact of factors other than storage duration on the metabolic phenotypes of stored RBC in a multicenter study. Within the framework of the REDS-III (Recipient Epidemiology and Donor Evaluation Study-III) RBC-Omics study, 13,403 donors were enrolled from four blood centers across the United States and tested for the propensity of their RBCs to hemolyze after 42 days of storage. Extreme hemolyzers were recalled and donated a second unit of blood. Units were stored for 10, 23, and 42 days prior to sample acquisition for metabolomics analyses. Unsupervised analyses of metabolomics data from 599 selected samples revealed a strong impact (14.2% of variance) of storage duration on metabolic phenotypes of RBCs. The blood center collecting and processing the units explained an additional 12.2% of the total variance, a difference primarily attributable to the storage additive (additive solution 1 vs. additive solution 3) used in the different hubs. Samples stored in mannitol-free/citrate-loaded AS-3 were characterized by elevated levels of high-energy compounds, improved glycolysis, and glutathione homeostasis. Increased methionine metabolism and activation of the transsulfuration pathway was noted in samples processed in the center using additive solution 1. Blood processing impacts the metabolic heterogeneity of stored RBCs from the largest multicenter metabolomics study in transfusion medicine to date. Studies are needed to understand if these metabolic differences influenced by processing/storage strategies impact the effectiveness of transfusions clinically.

Demographic and epidemiologic characterization of transfusion recipients from four US regions: evidence from the REDS-III recipient database.

Blood transfusion is one of the most common medical procedures during hospitalization in the United States. To understand the benefits of transfusion while mitigating potential risks, a multicenter database containing detailed information on transfusion incidence and recipient outcomes would facilitate research. The Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) program has developed a comprehensive transfusion recipient database utilizing data from hospital electronic health records at 12 participating hospitals in four geographic regions. Inpatient and outpatient data on transfusion recipients from January 1, 2013 to December 31, 2014 included patient age, sex, ethnicity, primary diagnosis, type of blood product provided, issue location, pretransfusion and post-transfusion hemoglobin (Hgb), and hospital outcomes. Transfusion incidence per encounter was calculated by blood product and various patient characteristics. During the 2-year study period, 80,362 (12.5%) inpatient encounters involved transfusion. Among inpatients, the most commonly transfused blood products were red blood cells (RBCs; 10.9% of encounters), followed by platelets (3.2%) and plasma (2.9%). Among patients who received transfusions, the median number of RBC units was one, the pretransfusion Hgb level was 7.6 g/dL, and the Hgb increment per unit was 1.4 g/dL. Encounter mortality increased with patient age, the number of units transfused, and the use of platelet or plasma products. The most commonly reported transfusion reaction was febrile nonhemolytic. The database contains comprehensive data regarding transfusion use and patient outcomes. The current report describes an evaluation of the first 2 years of a planned, 4-year, linked blood donor-component-recipient database, which represents a critical new resource for transfusion medicine researchers.