How do we leverage data through replication and warehousing to meet blood collection and transfusion service needs.

BACKGROUND: With the widespread adoption of Blood Establishment Computer Systems and other Blood Collection and Transfusion Service (BCTS) clinical information systems (CIS), electronic blood donor, product, and patient data are now routinely required for clinical, regulatory, operational, and quality needs. That data are often not readily accessible for such secondary use within CIS databases, particularly for applications with significant data availability requirements such as machine learning and artificial intelligence. Data replication provides one avenue by which CIS data can be made more readily available. STUDY DESIGN AND METHODS: Members of the AABB's Information Systems Committee along with institutional information technology colleagues provided a multi-institutional viewpoint on data replication through the lens of BCTS specific use cases. Case studies of informatics offerings leveraging such technologies were also elicited. RESULTS: Six distinct use cases describe the potential role of data replication including the creation of data warehouses for frontline laboratory staff. Specific BCTS examples for each use case are presented to highlight the value of data replication, including visualization of critical inventory (O red blood cells, HLA-compatible platelets) and utilization analytics for patient blood management. Two case studies describe the approach to implement such technologies to (1) optimize staffing via laboratory workload reporting and (2) improve access to blood via antigen-negative blood product location services. DISCUSSION: Data replication and warehousing can empower BCTS analytic offerings not otherwise natively available through one's CIS to improve patient care and laboratory operations.

Drivers of blood use in paediatric trauma: A retrospective cohort study.

OBJECTIVES: We asked whether age or injury severity drives blood use patterns in paediatric trauma. BACKGROUND: Transfusion for paediatric trauma care is complicated by known developmental differences in coagulation and injury patterns. METHODS/MATERIALS: We linked 10 years of Trauma Registry and blood bank data, 2011-2020, for all acute trauma patients aged <18 treated at a large US Level 1 adult and paediatric trauma centre. We assessed age, injury severity and mechanism for association with any blood use, use within the first 4 h of care, and resuscitation balance, using grouped-age Chi-square and multivariable regression models. RESULTS: Of 60 066 acute trauma arrivals at our centre in the study period, 7979 (13.3%) met inclusion criteria. Median age (IQR) was (7.6[2.4-14.5]); 6230(78.1%) were < 15 years old; 590(7.4%) received any blood products; and 128(1.6%) died. Among the 5842(73.2%) patients with impact-related injury, 2023(34.6%) met standards for severe injury (New Injury Severity Score [NISS] ≥ 16); 541(9.3%) were transfused, 171(31.6%) in the first 4 h and 72(13.3%) using ≥3 units of products in the first hour. Firearms injuries were the most severe, most likely to be transfused urgently, using balanced resuscitation, and to die (p < 0.001 for all). Multivariable logistic regression showed any blood use as strongly associated with NISS (Odds Ratio 1.124832; p < 0.0001; 95% CI 1.11-1.13) but not with age (OR 0.98; p = 0.07; 95% CI 0.96-1.00). CONCLUSION: Transfusion in the care of acute paediatric trauma is uncommon (<10% of injured minors in our cohorts received any blood products), and injury severity, particularly firearms injury-not age-drove transfusion.

Passive order auditing associated with reductions in red blood cell utilization: National blood shortage experience.

BACKGROUND: Decreased blood collection during the Coronavirus Disease 2019 (COVID-19) pandemic resulted in long-term red blood cell (RBC) shortages in the United States. In an effort to conserve RBCs, the existing passive alert system for auditing inpatient transfusions was modified to activate at a lower hemoglobin threshold (6.5 g/dL instead of 7.0 g/dL for stable, nonbleeding inpatients) during a 9-month shortage at an academic medical center. Hemoglobin levels prior to RBC transfusions were compared for inpatients receiving RBC transfusions to determine whether RBC utilization changed during the intervention. STUDY DESIGN AND METHODS: This retrospective study compared the number of single-unit RBC transfusions and hemoglobin levels prior to RBC transfusion among inpatients during the 9 months of the intervention (Period 2, 06/01/2021-2/28/2022) to the same period of the previous year (Period 1, 06/01/2020-2/28/2021). RESULTS: Overall full unit RBC transfusions to inpatients decreased by 15% from 5182 to 4421. Of all transfusions, 50.3% and 49.8% were single-unit RBC transfusions in Period 1 and Period 2, respectively. The incidence rate difference and incidence rate ratio of single RBC units transfused per 1000 patient days were significantly decreased (p = 0.0007). The average pre-transfusion hemoglobin level significantly decreased from 7.18 g/dL to 7.05 g/dL (p = 0.0002), largely due to significant decreases in hemoglobin transfusion triggers for adult inpatient ward transfusions. DISCUSSION: Modification of the passive alert system was associated with significantly decreased RBC utilization during a long-term RBC shortage. Modification of transfusion criteria recommended by passive alerts may be a feasible option to decrease RBC utilization at centers during long-term RBC shortages.

Application of Standardized Residual Component Culture Criteria for Suspected Septic Transfusion Reactions Would Increase the Component Culturing Rate at a Single Academic Medical Center.

OBJECTIVES: The 2019 SCARED study developed the Biomedical Excellence for Safer Transfusion (BEST) criteria in an effort to standardize the decision to culture residual units in the context of suspected septic transfusion reactions (STRs). The goal of this study was to apply the BEST criteria to determine the effect on the transfusion reaction decision to culture. METHODS: This retrospective, single-center, cross-sectional study assessed adult transfusion reactions identified in calendar years 2013 to 2020. Reactions following transfusion of RBCs, platelets, and plasma were included, and the decisions to culture following strict application of BEST criteria were compared with decisions to culture in actual practice. RESULTS: In total, 1,068 transfusion reactions were reported and 200 (19%) suspected STRs were cultured, all with negative results; 303 (28%) reactions would have been cultured per strict application of the BEST criteria. Concordance between actual culture decision and BEST criteria recommendation was 62% for cultured components and 79% for components that were not cultured. CONCLUSIONS: BEST criteria provide objective recommendations of when to culture residual units implicated in suspected STRs, but strict application of these criteria may result in increased culture rates. Clinical correlation to aid in the decision to culture is recommended.

Current state and positive impact of hospital-based blood donor centers in the United States.

BACKGROUND: The COVID-19 pandemic has brought tremendous challenges to the United States blood supply. Decreased collections have caused blood product shortages. The number of hospital-based donor centers (HBDCs) has decreased in the past decades, but they provide important support to their hospital systems. MATERIALS/METHODS: We identified 79 active HBDCs through an information request to the FDA. These centers were invited to participate in a survey about their activities, blood product collections, and perceived value. RESULTS: Thirty-six centers responded (46% response rate). The centers represented a wide range of states and geographic settings. Whole blood collection was most common, but some respondents also prepared specialized products such as COVID-19 convalescent plasma and pathogen-reduced platelets. Positive impacts of HBDCs included inventory availability, cost-effectiveness/savings, community outreach, supporting special patient populations, and collecting specialty products. All respondents anticipate at least stable operations, if not growth, in the future. CONCLUSION: HBDCs continue to be valuable assets in addressing emerging patient transfusion needs. Their unique offerings are tailored to the populations their hospitals support, and demonstrate the value in having the collection infrastructure in place to rapidly respond to critical shortages. This survey provides benchmark data about a broad group of HBDCs including products prepared, inventory self-sufficiency levels, and reasons for positive impact.

Comparison of Two Automated Immunoassays for the Detection of SARS-CoV-2 Nucleocapsid Antibodies.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel member of the coronavirus family that caused the global coronavirus 2019 (COVID-19) pandemic. The prevalence remains largely unknown because of early testing supply shortages. Although it cannot currently be used to determine level of immunity, antibody testing can contribute to epidemiological studies, identify convalescent plasma donors, or satisfy curiosity about previous exposure to the virus. METHODS: 407 samples collected from hospitalized inpatients with and without a confirmed SARS-CoV-2 infection, 170 remnant clinical specimens collected and frozen prior to the COVID-19 outbreak, and paired serum and plasma samples from 23 convalescent plasma donors were used to determine performance characteristics of the Abbott SARS-CoV-2 IgG and Roche Elecsys Anti-SARS-CoV-2 assays. The sensitivity, specificity, imprecision, interferences, and sample stability were determined. These assays were then used to characterize the antibody response in serial samples from 20 SARS-CoV-2 positive inpatients. RESULTS: Both assays exhibited 100% specificity (95% CI; 99.05-100.00), giving no positive results in 170 specimens collected before July 2019 and 215 specimens from patients without a confirmed SARS-CoV-2 infection. Differences between platforms were most notable in SARS-CoV-2 positive samples. Roche offered higher sensitivity in convalescent plasma donors at 95.7% (95% CI; 78.1-99.9) versus 91.3% (95% CI; 72.0-98.9) but Abbott detected antibodies in 2 immunocompromised patients whereas Roche did not. The Roche and Abbott platforms also exhibited different trends in antibody signal for a subset of patients. CONCLUSIONS: Both the Abbott and Roche platforms offer excellent specificity but different trends in antibody signal may reflect qualitative differences in the types of antibodies recognized by the 2 assays. Negative serologic results do not exclude previous SARS-CoV-2 infection.

Transfusion of blood components containing ABO-incompatible plasma does not lead to higher mortality in civilian trauma patients.

BACKGROUND: This study investigated the effect on mortality of transfusing ABO-incompatible plasma from all sources during trauma resuscitation. METHODS: Demographic, transfusion, and survival data were retrospectively extracted on civilian trauma patients. Patients were divided by receipt of any quantity of ABO-incompatible plasma from any blood product (incompatible group) or receipt of solely ABO-compatible plasma (compatible group). The primary outcome was 30-day mortality, while other outcomes included 6- and 24-hour mortality. Mixed-effects logistic regression was used to model the effect of various predictor variables, including receipt of incompatible plasma, on mortality outcomes. RESULTS: Nine hospitals contributed data on a total of 2618 trauma patients. There were 1282 patients in the incompatible group and 1336 patients in the compatible group. In both the unadjusted and adjusted models, the 6-hour, 24-hour, and 30-day mortality rates were not significantly different between these groups. The patients in the incompatible group were then divided into high volume (>342 mL) and low volume (≤342 mL) incompatible plasma recipients. In the adjusted model, the high-volume group had higher 24-hour mortality when the Trauma Injury Severity Score survival prediction was >50%. Mortality at 6 hours and 30 days was not higher in this model. The low-volume group did not have increased mortality at any of the time points in this adjusted model. CONCLUSION: The transfusion of incompatible plasma in civilian trauma resuscitation does not lead to higher 30-day mortality. The finding of higher mortality in a select group of recipients in the secondary analysis warrants further study.

Interference in the anti-Xa heparin activity assay due to hemolysis and icterus during pediatric extracorporeal life support.

Chromogenic anti-Xa assays for unfractionated heparin monitoring (heparin activity) are susceptible to interference from hemolysis and icterus. The purpose of this study was to better understand the effect of hemolysis and icterus on anti-Xa heparin activity and to predict the magnitude of the error. Increasing levels of hemoglobin and unconjugated bilirubin were added to pooled normal plasma or buffer containing known levels of heparin. Increased plasma hemoglobin or bilirubin produced falsely increased residual factor Xa activity as measured by the absorbance change (OD/min) in the Stago heparin activity assay. This increased absorbance change slope resulted in falsely lower estimates of heparin activity. The falsely lower heparin activity measurement occurred even when heparin was not present, indicating it was not due to heparin neutralization. In a sample containing 0.62 ± 0.06 U/mL heparin and 228 mg/dL hemoglobin, the measured heparin activity was 0.41 ± 0.03 U/mL, underestimating heparin activity by 0.21 ± 0.07 U/mL. Interference occurred if plasma hemoglobin was above 70 mg/dL or bilirubin was above 16 mg/dL, which happened in 16%-26% of samples from pediatric patients on extracorporeal life support (ECLS). In conclusion, hemolysis and icterus were common in ECLS patients, leading to underestimates of unfractionated heparin activity and potentially higher doses of heparin than intended. The magnitude of the heparin activity measurement error could be predicted based on plasma hemoglobin and bilirubin levels until these levels exceeded the technical limits of the assay, ~230 mg/dL hemoglobin and 55 mg/dL bilirubin.

Venous Thrombotic Risk in Transgender Women Undergoing Estrogen Therapy: A Systematic Review and Metaanalysis.

BACKGROUND: Transgender women are female individuals who were recorded men at birth based on natal sex. Supporting a person's gender identity improves their psychological health, and gender-affirming hormones reduce gender dysphoria and benefit mental health. For transgender women, estrogen administration has clinically significant benefits. Previous reviews have reported conflicting literature on the thrombotic risk of estrogen therapy in transgender women and have highlighted the need for more high-quality research. CONTENT: To help address the gap in understanding thrombotic risk in transgender women receiving estrogen therapy, we performed a systematic literature review and metaanalysis. Two evaluators independently assessed quality using the Ottawa Scale for Cohort Studies. The Poisson normal model was used to estimate the study-specific incidence rates and the pooled incidence rate. Heterogeneity was measured using Higgins I 2 statistic. The overall estimate of the incidence rate was 2.3 per 1000 person-years (95% CI, 0.8-6.9). The heterogeneity was significant (I 2 = 74%; P = 0.0039). SUMMARY: Our study estimated the incidence rate of venous thromboembolism in transgender women prescribed estrogen to be 2.3 per 1000 person-years, but because of heterogeneity this estimate cannot be reliably applied to transgender women as a group. There are insufficient data in the literature to partition by subgroup for subgroup prohibiting the analysis to control for tobacco use, age, and obesity, which is a major limitation. Additional studies of current estrogen formulations, modes of administration, and combination therapies, as well as studies in the aging transgender population, are needed to confirm thrombotic risk and clarify optimal therapy regimens.

Discordant Partial Thromboplastin Time (PTT) vs Anti-Xa Heparin Activity.

OBJECTIVES: To determine the relationship between baseline variations in the partial thromboplastin time (PTT) and the discordance between the PTT and anti-Xa heparin activity (anti-Xa) during heparin therapy. METHODS: The baseline PTT on heparin was determined using automated heparin neutralization with protamine (prPTT). The prPTT was used to calculate a baseline-corrected PTT on heparin to reduce discordance with anti-Xa measurements. RESULTS: The prPTT removed up to 1 U/mL of heparin, returning baseline values for normal, factor-deficient, and lupus inhibitor plasmas. A prolonged prPTT was seen in 97 (53%) of 182 samples from heparinized patients. The heparinized PTT was discordant compared with anti-Xa in 64 (35%) of 182 samples and 43 (67%) of 64 discordant samples, and 46% of concordant samples showed a prolonged prPTT. A baseline-corrected PTT reduced discordance with anti-Xa measurements by 64%. CONCLUSIONS: PTT/anti-Xa discordance due to baseline PTT prolongation could be reduced using a baseline-corrected PTT.

Severe ABO Hemolytic Disease of the Newborn Requiring Exchange Transfusion.

ABO incompatibility (ABOi), the most common cause of hemolytic disease of the newborn (HDN), is nearly always mild and treatable with phototherapy. Reports of ABOi HDN requiring neonatal exchange transfusion are extremely rare since the inception of modern guidelines. Here, a case of ABOi HDN clearly met criteria for exchange transfusion. An O-positive African American mother delivered a B-positive neonate that quickly developed hyperbilirubinemia. The neonatal DAT was positive from anti-B and anti-A,B, and maternal IgG titer was 1024. Double volume exchange transfusion resulted in a favorable outcome. Given early discharge of newborns, further understanding of factors predicting severe disease is needed.

Transfusion Support of Minority Patients: Extended Antigen Donor Typing and Recruitment of Minority Blood Donors.

One of the most important and persistent complications of blood transfusion is red blood cell (RBC) alloimmunization. When a patient is exposed to RBC antigens that differ from their own they can form alloantibodies to these foreign antigens. Blood group antigens are highly conserved and follow ancestral patterns of inheritance that may demonstrate population restriction. Minority populations who require chronic transfusion are at particularly high risk of alloimmunization when the blood donor population does not share the same ancestral background, resulting in exposure to non-self RBC antigens. It is incumbent on blood collectors to support patients with risk factors for alloimmunization as well as patients who have already formed alloantibodies. Increasing utilization of RBC genotyping may represent an opportunity to improve access to RBC units from donors that match the extended RBC phenotype of all possible patients.

Variability in, variability out: best practice recommendations to standardize pre-analytical variables in the detection of circulating and tissue microRNAs.

microRNAs (miRNAs) hold promise as biomarkers for a variety of disease processes and for determining cell differentiation. These short RNA species are robust, survive harsh treatment and storage conditions and may be extracted from blood and tissue. Pre-analytical variables are critical confounders in the analysis of miRNAs: we elucidate these and identify best practices for minimizing sample variation in blood and tissue specimens. Pre-analytical variables addressed include patient-intrinsic variation, time and temperature from sample collection to storage or processing, processing methods, contamination by cells and blood components, RNA extraction method, normalization, and storage time/conditions. For circulating miRNAs, hemolysis and blood cell contamination significantly affect profiles; samples should be processed within 2 h of collection; ethylene diamine tetraacetic acid (EDTA) is preferred while heparin should be avoided; samples should be "double spun" or filtered; room temperature or 4 °C storage for up to 24 h is preferred; miRNAs are stable for at least 1 year at -20 °C or -80 °C. For tissue-based analysis, warm ischemic time should be <1 h; cold ischemic time (4 °C) <24 h; common fixative used for all specimens; formalin fix up to 72 h prior to processing; enrich for cells of interest; validate candidate biomarkers with in situ visualization. Most importantly, all specimen types should have standard and common workflows with careful documentation of relevant pre-analytical variables.

Method-to-method variability in urine albumin measurements.

BACKGROUND: Urine albumin (uALB) is a useful marker in diagnosis and treatment of renal microvascular disease. Beckman Coulter recently re-formulated their uALB reagent for the AU series of instruments to increase the analytical measurement range (AMR). METHODS: Precision, linearity, reportable range, and analytical sensitivity for the reformulated reagent were determined using the AU680. In addition, the re-formulated AU reagent was compared to the previous generation AU reagent and to the Siemens Vista using residual urine specimens. The hook effect was evaluated on five instruments by spiking serum into albumin-free urine to generate a range of albumin concentrations. RESULTS: Precision and linearity within the AMR were confirmed, along with accuracy of dilutions to extend the reportable range. For patient sample correlation, the re-formulated reagent demonstrated a positive 11% bias relative to the original AU reagent and a negative 11% bias relative to the Vista. Concentrations of uALB >3000mg/dL produced falsely low results for both AU reagents. The DCA Vantage assay "hooked" at even lower uALB concentrations. CONCLUSIONS: The re-formulated AU uALB reagent met the manufacturer claimed performance characteristics. The AU and DCA Vantage were the only instruments of those tested affected by the hook effect in the concentration range evaluated. uALB assays are clearly not standardized, yet clinical guidelines dictate result interpretation. The method-to-method biases we observed here have the potential to lead to clinically significant post-analytical errors in uALB interpretation.

Mammogram image quality as a potential contributor to disparities in breast cancer stage at diagnosis: an observational study.

BACKGROUND: In an ongoing study of racial/ethnic disparities in breast cancer stage at diagnosis, we consented patients to allow us to review their mammogram images, in order to examine the potential role of mammogram image quality on this disparity. METHODS: In a population-based study of urban breast cancer patients, a single breast imaging specialist (EC) performed a blinded review of the index mammogram that prompted diagnostic follow-up, as well as recent prior mammograms performed approximately one or two years prior to the index mammogram. Seven indicators of image quality were assessed on a five-point Likert scale, where 4 and 5 represented good and excellent quality. These included 3 technologist-associated image quality (TAIQ) indicators (positioning, compression, sharpness), and 4 machine associated image quality (MAIQ) indicators (contrast, exposure, noise and artifacts). Results are based on 494 images examined for 268 patients, including 225 prior images. RESULTS: Whereas MAIQ was generally high, TAIQ was more variable. In multivariable models of sociodemographic predictors of TAIQ, less income was associated with lower TAIQ (p < 0.05). Among prior mammograms, lower TAIQ was subsequently associated with later stage at diagnosis, even after adjusting for multiple patient and practice factors (OR = 0.80, 95% CI: 0.65, 0.99). CONCLUSIONS: Considerable gains could be made in terms of increasing image quality through better positioning, compression and sharpness, gains that could impact subsequent stage at diagnosis.

Potentially missed detection with screening mammography: does the quality of radiologist's interpretation vary by patient socioeconomic advantage/disadvantage?

PURPOSE: We examined whether quality of mammography interpretation as performed by the original reading radiologist varied by patient sociodemographic characteristics. METHODS: For 149 patients residing in Chicago and diagnosed in 2005-2008, we obtained the original index mammogram that detected the breast cancer and at least one prior mammogram that did not detect the cancer performed within 2 years of the index mammogram. A single breast imaging specialist performed a blinded review of the prior mammogram. Potentially missed detection (PMD) was defined as an actionable lesion seen during a blinded review of the prior mammogram that was in the same quadrant as the cancer on the index mammogram. RESULTS: Of 149 prior mammograms originally read as nonmalignant, 46% (N = 68) had a potentially detectable lesion. In unadjusted analyses, PMD was greater among minority patients (54% vs. 39%, P = .07) and for patients with incomes below $30,000 (65% vs. 36%, P < .01), less education (58% vs. 39%, P = .02), and lacking private health insurance (63% vs. 40%, P = .02). Likelihood ratio tests for the inclusion of socioeconomic variables in multivariable logistic regression models were highly significant (P ≤ .02). CONCLUSIONS: Disadvantaged socioeconomic status appears to be associated with PMD of breast cancer at mammography screening.

Geographic and sociodemographic disparities in drive times to Joint Commission-certified primary stroke centers in North Carolina, South Carolina, and Georgia.

INTRODUCTION: Timely access to facilities that provide acute stroke care is necessary to reduce disabilities and death from stroke. We examined geographic and sociodemographic disparities in drive times to Joint Commission-certified primary stroke centers (JCPSCs) and other hospitals with stroke care quality improvement initiatives in North Carolina, South Carolina, and Georgia. METHODS: We defined boundaries for 30- and 60-minute drive-time areas to JCPSCs and other hospitals  by  using geographic information systems (GIS) mapping technology and calculated the proportions of the population living in these drive-time areas by sociodemographic characteristics. Age-adjusted county-level stroke death rates were overlaid onto the drive-time areas. RESULTS: Approximately 55% of the population lived within a 30-minute drive time to a JCPSC; 77% lived within a 60-minute drive time. Disparities in percentage of the population within 30-minute drive times were found by race/ethnicity, education, income, and urban/rural status; the disparity was largest between urban areas (70% lived within 30-minute drive time) and rural areas (26%). The rural coastal plains had the largest concentration of counties with high stroke death rates and the fewest JCPSCs. CONCLUSION: Many areas in this tri-state region lack timely access to JCPSCs. Alternative strategies are needed to expand provision of quality acute stroke care in this region. GIS modeling is valuable for examining and strategically planning the distribution of hospitals providing acute stroke care.