ABO O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an unpredictable, potentially catastrophic adverse effect resulting from an immune response to platelet factor 4 (PF4)/heparin complexes. We performed a genome-wide association study (GWAS) with positive functional assay as the outcome in a large discovery cohort of patients divided into 3 groups: (1) functional assay-positive cases (n = 1269), (2) antibody-positive (functional assay-negative) controls (n = 1131), and (3) antibody-negative controls (n = 1766). Significant associations (α = 5 × 10-8) were investigated in a replication cohort (α = 0.05) of functional assay-confirmed HIT cases (n = 177), antibody-positive (function assay-negative) controls (n = 258), and antibody-negative controls (n = 351). We observed a strong association for positive functional assay with increasing PF4/heparin immunoglobulin-G (IgG) level (odds ratio [OR], 16.53; 95% confidence interval [CI], 13.83-19.74; P = 1.51 × 10-209) and female sex (OR, 1.15; 95% CI, 1.01-1.32; P = .034). The rs8176719 C insertion variant in ABO was significantly associated with positive functional assay status in the discovery cohort (frequency = 0.41; OR, 0.751; 95% CI, 0.682-0.828; P = 7.80 × 10-9) and in the replication cohort (OR, 0.467; 95% CI, 0.228-0.954; P = .0367). The rs8176719 C insertion, which encodes all non-O blood group alleles, had a protective effect, indicating that the rs8176719 C deletion and the O blood group were risk factors for HIT (O blood group OR, 1.42; 95% CI, 1.26-1.61; P = 3.09 × 10-8). Meta-analyses indicated that the ABO association was independent of PF4/heparin IgG levels and was stronger when functional assay-positive cases were compared with antibody-positive (functional assay-negative) controls than with antibody-negative controls. Sequencing and fine-mapping of ABO demonstrated that rs8176719 was the causal single nucleotide polymorphism (SNP). Our results clarify the biology underlying HIT pathogenesis with ramifications for prediction and may have important implications for related conditions, such as vaccine-induced thrombotic thrombocytopenia.

A randomized control trial to compare mortality in recipients of leucoreduced and non-leucoreduced whole blood transfusion in patients with cancer in Uganda.

BACKGROUND: Mortality benefit of transfusion with leucoreduced whole blood has not been demonstrated in the sub-Saharan Africa (SSA). We compared mortality in patients with cancer transfused with leucoreduced and non-leucoreduced whole blood in a SSA setting. METHODS: An open-label randomized controlled trial was conducted at the Uganda Cancer Institute where participants were randomized in a 1:1 ratio into the leucoreduced and non-leucoreduced whole blood transfusion arms. Leucocyte filtration of whole blood was performed within 72 h of blood collection. Patients aged ≥ 15 years who were prescribed blood transfusion by the primary physicians were eligible for study enrolment. Mortality difference was analyzed using intention-to-treat survival analysis and cox proportional hazard model was used to analyze factors associated with mortality. RESULTS: There were 137 participants randomized to the leucoreduced and 140 to the non-leucoreduced arms. Baseline characteristics were similar between the two arms. The median number of blood transfusions received was 1 (IQR, 1-3) unit and 2 (IQR, 1-3) units in the leucoreduced and non-leucoreduced arms respectively, p = 0.07. The 30-day mortality rate in the leucoreduced arm was 4.6% (95% CI, 2.1-10) and was 6.2% (95% CI, 3.2-12.1) in the non-leucoreduced arm (p = 0.57), representing an absolute effect size of only 1.6%. Increasing age (HR = 0.92, 95% CI, 0.86-0.98, p = 0.02) and Eastern Co-operative Oncology Group (ECOG) performance score of 1 (HR = 0.03, 95% CI, 0.00-0.31, p < 0.01) were associated with reduced 30-day mortality. CONCLUSIONS: The study failed to demonstrate mortality difference between cancer patients transfused with leucoreduced and non-leucoreduced whole blood. Although this study does not support nor refute universal leucoreduction to reduce mortality in patients with cancer in SSA, it demonstrates the feasibility of doing transfusion RCTs in Uganda, where a multi-center trial with an appropriate sample size is needed. TRIAL REGISTRATION: Pan African Clinical Trial Registry, https://pactr.samrc.ac.za/ (PACTR202302787440132). Registered on 06/02/2023.

Reducing blood product wastage through the inter-hospital redistribution of near-outdate inventory.

BACKGROUND: Hospital transfusion services order blood products to satisfy orders and maintain inventory levels during unexpected periods of increased blood demand. Surplus inventory may outdate before being allocated to a recipient. Blood product outdating is the largest contributor to blood wastage. STUDY DESIGN: A province-wide redistribution program was designed and implemented to redistribute near-outdate plasma protein and related blood products from low-usage to high-usage hospitals. Program operations and details are described in this paper. Two transport container configurations were designed and validated for transport of all blood products. A cost-analysis was performed to determine the effectiveness of this redistribution program. RESULTS: A total of 130 hospital transfusion services contributed at least one near-outdate blood product for redistribution between January 2012 and March 2020. These services redistributed 15,499 products through 3412 shipments, preventing the outdating of $17,570,700 CAD worth of product. Program costs were $14,900 for shipping and $30,000 for staffing. Failed time limits or non-compliance with packing configurations resulted in $388,200 worth of blood products (97 shipments containing 816 products) being discarded. Courier transport delays was the most common reason (42/97; 43%) for transport failure. CONCLUSION: Redistributing near-outdate blood products between hospitals is a feasible solution to minimize outdating. Despite heterogeneity of Canadian blood product inventory, all products (each with unique storage and transport requirements) were successfully redistributed in one of two validated and simple containers. Total operation costs of this program were small in comparison to the $17.6 million in savings associated with preventing the discard of outdated products.

Red cell transfusion thresholds in outpatients with myelodysplastic syndromes: Results of a pilot randomized trial RBC-ENHANCE.

BACKGROUND: The optimal hemoglobin (Hb) threshold for red blood cell transfusions in adult patients with myelodysplastic syndromes (MDS) has not been defined. STUDY DESIGN AND METHODS: We conducted a pilot randomized multi-center study of two transfusion algorithms (liberal, to maintain Hb 110-120 g/L, transfuse 2 units if Hb < 105 g/L and 1 unit if Hb 105-110 g/L vs. restrictive, 85-105 g/L, transfuse 2 units when Hgb < 85 g/L). Primary objectives were 70% compliance in maintaining the q2 week hemoglobin within the targeted range and the achievement of a 15 g/L difference in pre-transfusion Hb. Secondary outcomes included measures of quality of life (QOL), iron studies and safety. RESULTS: Twenty-eight patients were randomized between February 2015-2020, 13 to the restrictive arm and 15 to the liberal arm in three tertiary care centers. The compliance was 66% and 45% and the mean pre-transfusion Hb thresholds were 86 (standard deviation [SD] 8) and 98 g/L (SD 10) in the restrictive and liberal arms, (mean difference 11.8 g/L, p < .0001), respectively. Patients in the liberal arm experienced a mean of 3.4 (SD 2.6) more transfusion visits and received a mean of 5.3 (SD 5.5) more units of blood during the 12-week study. Ferritin increased by 1043 (SD 1516) IU/L and 148 (SD 1319) IU/L in the liberal and restrictive arms, respectively. Selected QOL scores were superior pre-transfusion and more patients achieved clinically important improvements in the liberal arm compared with the restrictive arm for selected symptoms and function domains. CONCLUSION: The results establish that policies for transfusion support can be delivered in practice at multiple hospitals, but further research is required to understand the full clinical effects and safety of liberal transfusion policies in MDS outpatients.

Quality of life and cost-effectiveness of convalescent plasma compared to standard care for hospitalized COVID-19 patients in the CONCOR-1 trial.

BACKGROUND: The CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID-19 patients. This study evaluates the cost-effectiveness of convalescent plasma and its impact on quality-of-life to provide insight into its potential as an alternative treatment in resource-constrained settings. METHODS: Individual patient data on health outcomes and resource utilization from the CONCOR-1 trial were used to conduct the analysis from the Canadian public payer's perspective with a time horizon of 30 days post-randomization. Baseline and 30-day EQ-5D-5L were measured to calculate quality-adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ-5D-5L scores of hospitalized inpatients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled were used. The sensitivity analysis utilizes EQ-5D-5L scores from the same population but only uses costs from this population. RESULTS: 940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ-5D-5L scores were 0.61 in both arms (p = .85) at baseline. At 30 days, EQ-5D-5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms, respectively (p = .46). The incremental cost was $4458 and the incremental quality-adjusted life day was -0.078. DISCUSSION: Convalescent plasma was less effective and more costly than standard care in treating hospitalized COVID-19.

KEL1 negative red cell transfusions for females of current or future child-bearing potential: A clinical impact and feasibility study.

BACKGROUND: Anti-K is an alloantibody stimulated in response to the KEL1 antigen and may cause hemolytic disease of the fetus and newborn (HDFN). Provision of KEL1 negative blood to females of child-bearing potential was not our practice. We assessed the impact of our policy and assessed feasibility of a KEL1 negative transfusion policy. STUDY DESIGN AND METHODS: This is a cohort study spanning Jan 1, 2007-Jun 30, 2017 in Hamilton, Canada. Data were obtained via our institution's transfusion database. Chart reviews of females age ≤45 with anti-K were performed; data on RBC KEL1 phenotype were obtained from the blood supplier when needed to ascertain the cause of alloimmunization. Descriptive analysis of hospital KEL1 negative inventory demand and supply was performed. RESULTS: From Jan 2007-Jun 2017, 8.6% of all RBC units transfused were provided to females age ≤45. There were 111 females with detectable anti-K. Median age at time of antibody detection was 34 years (interquartile range 27-40) and 28 of 111 (25.2%) patients may have been alloimmunized by transfusion. Of 49 pregnancies, seven had complications due to anti-K. We estimated that our existing RBC inventory (with 16% units known to be KEL1 negative in 2017) is sufficient to meet demand and support a KEL1 negative transfusion policy for females age ≤45. CONCLUSION: Transfusion was responsible for alloimmunization in 25% of females with anti-K over 10 years. Analysis of supply and demand can be used to inform feasibility of a KEL1 negative transfusion policy.

An unsupervised learning approach to identify immunoglobulin utilization patterns using electronic health records.

BACKGROUND: Managing Canada's immunoglobulin (Ig) product resource allocation is challenging due to increasing demand, high expenditure, and global shortages. Detection of groups with high utilization rates can help with resource planning for Ig products. This study aims to uncover utilization subgroups among the Ig recipients using electronic health records (EHRs). METHODS: The study included all Ig recipients (intravenous or subcutaneous) in Calgary from 2014 to 2020, and their EHR data, including blood inventory, recipient demographics, and laboratory test results, were analyzed. Patient clusters were derived based on patient characteristics and laboratory test data using K-means clustering. Clusters were interpreted using descriptive analyses and visualization techniques. RESULTS: Among 4112 recipients, six clusters were identified. Clusters 1 and 2 comprised 408 (9.9%) and 1272 (30.9%) patients, respectively, contributing to 62.2% and 27.1% of total Ig utilization. Cluster 3 included 1253 (30.5%) patients, with 86.4% of infusions administered in an inpatient setting. Cluster 4, comprising 1034 (25.1%) patients, had a median age of 4 years, while clusters 2-6 were adults with median ages of 46-60. Cluster 5 had 62 (1.5%) patients, with 77.3% infusions occurring in emergency departments. Cluster 6 contained 83 (2.0%) patients receiving subcutaneous Ig treatments. CONCLUSION: The results identified data-driven segmentations of patients with high Ig utilization rates and patients with high risk for short-term inpatient use. Our report is the first on EHR data-driven clustering of Ig utilization patterns. The findings hold the potential to inform demand forecasting and resource allocation decisions during shortages of Ig products.

An evaluation of the clinical impacts of 7-day platelets.

BACKGROUND: In August 2017, Canadian Blood Services extended the shelf-life of platelet concentrates from 5 to 7 days. The clinical impacts of this policy change remain unclear. STUDY DESIGN AND METHODS: We used a before-after retrospective design of platelet-transfused adult inpatients in Hamilton, ON, Canada. Data were captured for 18 months before (Period 1: February 2016-July 2017) and 18 months after (Period 2: September 2017-February 2019) 7-day platelet implementation. Primary outcome was absolute platelet count increment (ACI) in univariate and multivariate analyses adjusted for confounders. Data were obtained from our institution's transfusion database, Ontario's Transfusion Transmitted Injuries Surveillance System, and the blood supplier. RESULTS: Overall, 1360 patients with single dose platelet transfusions were included in Period 1 and 1211 patients in Period 2. Median age at admission was 66 years, and approximately 40% of patients underwent cardiac surgery. Using a non-inferiority margin of -10 × 109 /L, platelets transfused during the 7-day storage period were non-inferior to those transfused in the 5-day storage period [mean count difference - 4.63 × 109 /L (95% CI -7.40 to -1.87, p = 0.0001)]. However, platelet ACIs following transfusion consistently trended lower in the 7-day group for all patients and subgroups. No differences in secondary clinical outcomes were observed. Platelet expiry reduced from 8.1 to 6.3% (p < 0.0001). CONCLUSION: Platelet transfusions following 7-day storage policy were non-inferior to transfusions in the 5-day policy period, although reduced ACIs were observed. There were no increases in adverse clinical outcomes.

Exploring the potential harm of varied blood storage on patients undergoing cardiovascular surgery.

BACKGROUND AND OBJECTIVES: Debate exists surrounding the optimal duration of red blood cell (RBC) storage. A hypothesis emerging from previous research suggests that exposure to fresh blood may be harmful to patients undergoing cardiac surgery. This study uses a large transfusion medicine database to explore the association between in-hospital mortality and red cell storage duration. MATERIALS AND METHODS: This is an exploratory retrospective cohort study of all adult patients at Hamilton, Canada, over a 14-year period that received at least one allogeneic red cell transfusion during their hospitalization for cardiac surgery requiring bypass. The primary outcome for the study was in-hospital death. Analysis was performed using multivariate Cox regression modelling with time-dependent and time-independent covariates and stratification variables. Five models with varying definitions for short, intermediate and prolonged duration of RBC storage were tested. RESULTS: From March 2004 to December 2017, 11,205 patients met the inclusion criteria and were included in the regression analyses. No significant effect of short-duration red storage on patient mortality was observed in all statistical models, with the red cells stored for the longest duration as the reference group. When patients who received exclusively fresh (hazard ratio [HR] 1.040, 95% confidence interval [CI] 0.588-1.841, p-value = 0.893) and older aged (HR 1.038, 95% CI 0.769-1.1.402, p-value = 0.0801) RBCs were compared with those who received exclusively mid-age red cells as the reference, statistical significance was similarly not reached. CONCLUSION: Red cells stored for the shortest duration are not associated with increased risk of mortality among cardiac surgery patients.

A positive blood culture is associated with a lower haemoglobin increment in hospitalized patients after red blood cell transfusion.

BACKGROUND AND OBJECTIVES: Abundant clinical evidence supports the safety of red blood cell (RBC) concentrates for transfusion irrespective of storage age, but still, less is known about how recipient characteristics may affect post-transfusion RBC recovery and function. Septic patients are frequently transfused. We hypothesized that the recipient environment in patients with septicaemia would blunt the increase in post-transfusion blood haemoglobin (Hb). The main objective was to compare the post-transfusion Hb increment in hospitalized patients with or without a positive blood culture. MATERIALS AND METHODS: A retrospective cohort study using data from the Transfusion Research, Utilization, Surveillance, and Tracking database (TRUST) was performed. All adult non-trauma in-patients transfused between 2010 and 2017 with ≥1 RBC unit, and for whom both pre- and post-transfusion complete blood count and pre-transfusion blood culture data were available were included. A general linear model with binary blood culture positivity was fit for continuous Hb increment after transfusion and was adjusted for patient demographic parameters and transfusion-related covariates. RESULTS: Among 210,263 admitted patients, 6252 were transfused: 596 had positive cultures, and 5656 had negative blood cultures. A modelled Hb deficit of 1.50 g/L in blood culture-positive patients was found. All covariates had a significant effect on Hb increment, except for the age of the transfused RBC. CONCLUSION: Recipient blood culture positivity was associated with a statistically significant but modestly lower post-transfusion Hb increment in hospitalized patients. In isolation, the effect is unlikely to be clinically significant, but it could become so in combination with other recipient characteristics.

A retrospective analysis of haemolytic reactions to intravenous immunoglobulin using data from the Transfusion-Transmitted Injuries Surveillance System (Ontario).

BACKGROUND AND OBJECTIVES: Haemolysis can occur following intravenous immunoglobulin (IVIG) infusion. Haemovigilance data were analysed using a novel approach for including two control groups with no haemolysis to IVIG. Objectives included a summary of all reactions to IVIG, rate estimates and analysis of haemolytic reactions including risk factors. MATERIALS AND METHODS: Canadian haemovigilance data from Ontario (2013-2021), IVIG distribution and transfusion data from the blood supplier, and data from a large local transfusion registry were used. An 'other-reactions' control group included patients with IVIG reactions that were not haemolytic, and registry patients with no-reaction were the 'no-reaction controls'. Descriptive analysis and two logistic regression models for the different control groups were performed. RESULTS: One thousand one hundred and seventy reactions were included. Most common were febrile non haemolytic (26.1%), minor allergic (24.5%) and IVIG headache (15.3%) followed by haemolytic 10.9% (128/1170). Haemolytic reaction rates decreased over time: rates since 2020 estimated between 1.5 and 2.9/1000 kg IVIG used. The regression model for other-reaction controls identified two risk factors for haemolysis: non-O blood group recipients compared with group O recipients (p value = 0.0106) and IVIG dose per 10 g increase (OR 1.359; 95% CI 1.225-1.506). The model using no-reaction controls gave similar results and also showed no pre-medication was associated with a higher risk of haemolysis (OR 29.084; 95% CI 1.989-425.312). CONCLUSION: The frequency of haemolytic reactions has decreased over time. We confirmed non-O blood group recipients and IVIG dose as risk factors for haemolysis and raise the hypothesis that no pre-medication may increase the risk of haemolysis.

A data-driven approach to determine daily platelet order quantities at hospitals.

BACKGROUND: Determining the required daily number of platelet units in hospitals is a challenging task due to the high uncertainty in daily usage and short shelf life of platelets. STUDY DESIGN AND METHODS: We developed a linear prediction model to guide the daily ordering quantity of platelet units at a hospital that orders the required units from a central supplier. The predictive model relies on historical demand data and other information from the hospital's information system. The ordering strategy is to place an order at the end of each day to bring the platelet inventory to the predicted demand for the next day. Unlike typical prediction models, the quality of the predictions is measured with respect to the resulting inventory costs of wastage and shortage. We used data from two hospitals in Hamilton, Ontario from 2015 to 2016 to train our model and evaluated its performance based on the resulting wastage and shortage rates in 2017. RESULTS: In 2017, respectively 1915 and 4305 platelet units were transfused at the two hospitals, with daily average (SD) usage of 5.2 (3.7) and 11.8 (4.4). The expiry (estimated shortage) rates were 8.67% (13.86%), and 2.28% (8.48%) at the two hospitals, respectively. Our baseline model would have reduced the expiry (shortage) rates to 2.54% (4.01%) and 0.05% (0.44%) for the two hospitals, respectively. DISCUSSION: Guiding daily ordering decisions for platelets using our proposed model could lead to a significant reduction of wastage and shortage rates at hospitals.

From demand forecasting to inventory ordering decisions for red blood cells through integrating machine learning, statistical modeling, and inventory optimization.

BACKGROUND: The demand and supply of blood are highly variable over time. Blood inventory management that relies heavily on experience-based decisions may not be adaptive to real demand, leading to high operational costs, wastage, and shortages. METHODS: We combined statistical modeling, machine learning, and optimization methods to develop a data-driven demand forecasting and inventory management strategy for red blood cells (RBCs). We then used the strategy to inform daily blood orders. A secondary semi-weekly (twice per week) ordering strategy was developed to handle the last-mile split delivery problem for blood suppliers, characterized by multi-deliveries to the same location multiple times during a short period of time. Both strategies were evaluated using the TRUST database including all patient data across four hospitals in Hamilton, Ontario. RESULTS: We identified 227,944 RBC transfusions for 40,787 patients in Hamilton, Ontario from 2012 to 2018. The predicted daily demand from the hybrid demand forecasting model was not significantly different from the actual daily demand (paired t-test p-value = 0.163); however, the proposed daily ordering quantity from the model was significantly lower than the actual ordering quantity (p-value <0.001). The proposed daily ordering strategy reduced inventory levels by 38.4% without risk of shortages, leading to an overall cost reduction of 43.0% (95% confidence interval [CI]: 42.3%, 43.7%) compared with the actual cost. The semi-weekly ordering strategy reduced ordering frequency by 62.6% (95% CI: 61.5%, 63.7%). CONCLUSION: The proposed data-driven ordering strategy combining demand forecasting and inventory optimization can achieve significant cost savings for healthcare systems and blood suppliers.

A data-informed system to manage scarce blood product allocation in a randomized controlled trial of convalescent plasma.

BACKGROUND: Equitable allocation of scarce blood products needed for a randomized controlled trial (RCT) is a complex decision-making process within the blood supply chain. Strategies to improve resource allocation in this setting are lacking. METHODS: We designed a custom-made, computerized system to manage the inventory and allocation of COVID-19 convalescent plasma (CCP) in a multi-site RCT, CONCOR-1. A hub-and-spoke distribution model enabled real-time inventory monitoring and assignment for randomization. A live CCP inventory system using REDCap was programmed for spoke sites to reserve, assign, and order CCP from hospital hubs. A data-driven mixed-integer programming model with supply and demand forecasting was developed to guide the equitable allocation of CCP at hubs across Canada (excluding Québec). RESULTS: 18/38 hospital study sites were hubs with a median of 2 spoke sites per hub. A total of 394.5 500-ml doses of CCP were distributed; 349.5 (88.6%) doses were transfused; 9.5 (2.4%) were wasted due to mechanical damage sustained to the blood bags; 35.5 (9.0%) were unused at the end of the trial. Due to supply shortages, 53/394.5 (13.4%) doses were imported from Héma-Québec to Canadian Blood Services (CBS), and 125 (31.7%) were transferred between CBS regional distribution centers to meet demand. 137/349.5 (39.2%) and 212.5 (60.8%) doses were transfused at hubs and spoke sites, respectively. The mean percentages of total unmet demand were similar across the hubs, indicating equitable allocation, using our model. CONCLUSION: Computerized tools can provide efficient and immediate solutions for equitable allocation decisions of scarce blood products in RCTs.

Prolonged Blood Storage and Risk of Posttransfusion Acute Kidney Injury.

BACKGROUND: Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. METHODS: The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. RESULTS: The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. CONCLUSIONS: In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury.

A cross-sectional study of haemolytic disease of the newborn in Uganda.

BACKGROUND AND OBJECTIVES: Haemolytic disease of the newborn (HDN) is an immune haemolytic anaemia from maternal alloantibodies. Rh immunoglobulin (RhIg) prophylaxis can prevent alloimmunization to the D antigen. However, RhIg is not universally available in Uganda. ABO incompatibility also causes HDN. We determined the prevalence of HDN among newborn infants with jaundice in Uganda. MATERIALS AND METHODS: We conducted a prospective cross-sectional study at Kawempe National Referral Hospital, Kampala, Uganda. Infants aged 0-14 days with neonatal jaundice (or total bilirubin >50 µmol/L) were enrolled. Clinical evaluation and laboratory testing, including ABO, RhD typing and maternal antibody screen, were performed. RESULTS: A total of 466 babies were enrolled. The mean (SD) age was 3.4 (1.5) days. Of newborn babies with jaundice, 17.2% (80/466) had HDN. Babies with HDN had lower haemoglobin (SD); 15.7 (2.7) compared with those without HDN; 16.4 (2.4) g/dL, p = 0.016; and a higher bilirubin (interquartile range); 241 (200-318) compared with those without HDN; 219 (191-263) µmol/L, p < 0.001. One baby had anti-D HDN, while 46/466 had HDN from an ABO incompatibility (anti-A 43.5% and anti-B 56.5%); 82% of babies with HDN also had suspected neonatal sepsis or birth asphyxia. About 79.2% (57/72) of mothers did not have ABO/Rh blood group performed antenatally. All infants with HDN survived except one. CONCLUSION: Among newborn infants with jaundice, HDN is not rare. The majority is due to ABO HDN affecting group A and group B babies equally. Ensuring routine ABO/Rh grouping for all pregnant women is an area for improvement.

Plasma transfusion practices: A multicentre electronic audit.

BACKGROUND AND OBJECTIVES: Plasma is often transfused to patients with bleeding or requiring invasive procedures and with abnormal tests of coagulation. Chart audits find half of plasma transfusions unnecessary, resulting in avoidable complications and costs. This multicentre electronic audit was conducted to determine the proportion of plasma transfused without an indication and/or at a sub-therapeutic dose. METHODS: Data were extracted on adult inpatients in 2017 at five academic sites from the hospital electronic chart, laboratory information systems and the Canadian Institute for Health Information Discharge Abstract Database. Electronic criteria for plasma transfusion outside recommended indications were: (1) international normalized ratio (INR) < 1.5 with no to moderate bleeding; (2) INR ≥ 1.5, with no to mild bleeding and no planned procedures; and (3) no INR before or after plasma infusion. Sub-therapeutic dose was defined as ≤2 units transfused. RESULTS: In 1 year, 2590 patients received 6088 plasma transfusions encompassing 11,490 units of plasma occurred at the five sites. 77.7% of events were either outside indications or under-dosed. Of these, 34.8% of plasma orders had no indication identified, and 62% of these occurred in non-bleeding patients and no planned procedure with an isolated elevated INR. 70.7% of transfusions were under-dosed. Most plasma transfusions occurred in the intensive care unit or the operating room. Inter-hospital variability in peri-transfusion testing and dosing was observed. CONCLUSION: The majority of plasma transfusions are sub-optimal. Local hospital culture may be an important driver. Electronic audits, with definitions employed in this study, may be a practical alternative to costly chart audits.

Exploring the components of bleeding outcomes in transfusion trials for patients with hematologic malignancy.

Clinically significant bleeding in patients with hematologic malignancies is a heterogeneous composite outcome currently defined as World Health Organization (WHO) bleeding Grades 2, 3, and 4. However, the clinical significance of some minor bleeds categorized as WHO Grades 1 and 2 remains controversial. We analyzed the number and frequency of individual signs and symptoms of WHO Grades 1 and 2 bleeds and explored their association with more severe incident bleeds graded as WHO Grades 3 and 4. STUDY DESIGN AND METHODS: We aggregated daily bleeding assessment data from three randomized controlled trials conducted in patients with hematologic malignancies that used bleeding as an outcome. Cox proportional hazard regression analysis was used to identify signs and symptoms categorized as WHO Grades 1 and 2 bleeds that were associated with more severe bleeds (Grades 3 and 4). RESULTS: We collected data from 315 patients (n = 5476 daily bleeding assessments; 3383 [61.8%] with a bleed documented). A total of 98.3% (3326/3383) were Grade 1 and 2 bleeds and 1.7% (57/3383) were Grades 3 and 4. Grade 1 and 2 bleeds were composed of 20 different bleeding signs and symptoms. Hematuria (hazard ratio, 16.1; 95% confidence interval, 4.4-59.2; P < .0001) was associated with incident Grade 3 or 4 bleeds. CONCLUSION: In patients with hematologic malignancy, only hematuria (microscopic and/or macroscopic) was associated with more severe incident bleeds. This findings require validation in independent data sets.

Necrotizing enterocolitis and mortality after transfusion of ABO non-identical blood.

BACKGROUND: The relationship between ABO non-identical transfusion and the outcomes of necrotizing enterocolitis (NEC), and all-cause mortality in very-low birth weight (VLBW) neonates receiving red blood cell transfusion is unknown. STUDY DESIGN AND METHODS: A retrospective multicenter cohort study was conducted in VLBW neonates in neonatal intensive care units between 2004 and 2016. VLBW (≤1500 grams) neonates were followed until discharge or in-hospital death. The primary exposure was ABO group. Secondary exposures included platelet count, plasma transfusions, and maternal ABO group. Outcome measures were NEC (defined as Bell stage ≥ 2) and all-cause mortality. Time-dependent Cox regression models with competing risks were used to investigate factors associated with NEC and mortality. RESULTS: Thousand and sixteen neonates were included with 10.8% developing NEC (n = 110) and 14.1% mortality (n = 143). Platelet count (hazard ratio [HR] = 0.995; 95% confidence interval [CI]: 0.922-0.998) and number of plasma transfusions (HR = 2.908; 95% CI:1.265-6.682) were associated with NEC, while ABO group (non-O vs. O) was not (HR = 0.761; 95% CI: 0.393-1.471). Higher all-cause mortality occurred in neonates without NEC who were non-O compared with O (HR = 17.5; 95% CI: 1.784-171.692), but not in neonates with NEC (HR = 1.112; 95% CI: 0.142-8.841). Plasma transfusion was associated with increased mortality in both groups. DISCUSSION: ABO non-identical transfusion was not associated with NEC or mortality in neonates with NEC. It was associated with increased mortality in neonates without NEC. As many neonatal intensive care units transfuse only O group blood as routine practice, future trials are needed to investigate the association between this practice and neonatal mortality.

Hemostatic efficacy of pathogen-inactivated vs untreated platelets: a randomized controlled trial.

Pathogen inactivation of platelet concentrates reduces the risk for blood-borne infections. However, its effect on platelet function and hemostatic efficacy of transfusion is unclear. We conducted a randomized noninferiority trial comparing the efficacy of pathogen-inactivated platelets using riboflavin and UV B illumination technology (intervention) compared with standard plasma-stored platelets (control) for the prevention of bleeding in patients with hematologic malignancies and thrombocytopenia. The primary outcome parameter was the proportion of transfusion-treatment periods in which the patient had grade 2 or higher bleeding, as defined by World Health Organization criteria. Between November 2010 and April 2016, 469 unique patients were randomized to 567 transfusion-treatment periods (283 in the control arm, 284 in the intervention arm). There was a 3% absolute difference in grade 2 or higher bleeding in the intention-to-treat analysis: 51% of the transfusion-treatment periods in the control arm and 54% in the intervention arm (95% confidence interval [CI], -6 to 11; P = .012 for noninferiority). However, in the per-protocol analysis, the difference in grade 2 or higher bleeding was 8%: 44% in the control arm and 52% in the intervention arm (95% CI -2 to 18; P = .19 for noninferiority). Transfusion increment parameters were ∼50% lower in the intervention arm. There was no difference in the proportion of patients developing HLA class I alloantibodies. In conclusion, the noninferiority criterion for pathogen-inactivated platelets was met in the intention-to-treat analysis. This finding was not demonstrated in the per-protocol analysis. This trial was registered at The Netherlands National Trial Registry as #NTR2106 and at www.clinicaltrials.gov as #NCT02783313.