Effect of Donor Sex on Recipient Mortality in Transfusion.

BACKGROUND: Conflicting observational evidence exists regarding the association between the sex of red-cell donors and mortality among transfusion recipients. Evidence to inform transfusion practice and policy is limited. METHODS: In this multicenter, double-blind trial, we randomly assigned patients undergoing red-cell transfusion to receive units of red cells from either male donors or female donors. Patients maintained their trial-group assignment throughout the trial period, including during subsequent inpatient and outpatient encounters. Randomization was conducted in a 60:40 ratio (male donor group to female donor group) to match the historical allocation of red-cell units from the blood supplier. The primary outcome was survival, with the male donor group as the reference group. RESULTS: A total of 8719 patients underwent randomization before undergoing transfusion; 5190 patients were assigned to the male donor group, and 3529 to the female donor group. At baseline, the mean (±SD) age of the enrolled patients was 66.8±16.4 years. The setting of the first transfusion was as an inpatient in 6969 patients (79.9%), of whom 2942 (42.2%) had been admitted under a surgical service. The baseline hemoglobin level before transfusion was 79.5±19.7 g per liter, and patients received a mean of 5.4±10.5 units of red cells in the female donor group and 5.1±8.9 units in the male donor group (difference, 0.3 units; 95% confidence interval [CI], -0.1 to 0.7). Over the duration of the trial, 1141 patients in the female donor group and 1712 patients in the male donor group died. In the primary analysis of overall survival, the adjusted hazard ratio for death was 0.98 (95% CI, 0.91 to 1.06). CONCLUSIONS: This trial showed no significant difference in survival between a transfusion strategy involving red-cell units from female donors and a strategy involving red-cell units from male donors. (Funded by the Canadian Institutes of Health Research; iTADS ClinicalTrials.gov number, NCT03344887.).

A global analysis of the use of immunoglobulin, shortages in supply, and mitigating measures: A survey of hospital providers (a BEST Collaborative study).

BACKGROUND: Immunoglobulin (IG) therapy is widely used to treat primary and secondary immune deficiencies and as immunomodulatory agent for various disorders. There is great concern that shortages of IG may rise, potentially affecting medical treatment options. STUDY DESIGN AND METHODS: An international survey was developed to study how intravenous immunoglobulins (IVIGs) are used and managed within hospitals in case of shortages. Study data were collected and managed using REDCap electronic data capture tools hosted by the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. The survey was directed to hospital pharmacists and blood bank transfusion professionals and disseminated through members of the BEST Collaborative network. RESULTS: Survey respondents from institutions in the USA, Canada, Europe, Japan, and Australia (n = 13) confirmed that the primary specialties utilizing IG are neurology, hematology, and immunology. More than 60% of respondents reported IG supply shortages, but mitigation strategies were not well developed. DISCUSSION: As IG is the leading driver in plasma demand, more studies are needed to understand current and future demand for IG from the clinical perspective. Necessity lies in establishing clinical guidance to address shortages.

How do we achieve blinding in modern electronic and paper medical records during the conduct of transfusion trials?

BACKGROUND: Regulatory aspects of transfusion medicine add complexity in blinded transfusion trials when considering various electronic record keeping software and blood administration processes. The aim of this study is to explore strategies when blinding transfusion components and products in paper and electronic medical records. METHODS: Surveys were collected and interviews were conducted for 18 sites across various jurisdictions in North America to determine solutions applied in previous transfusion randomized control trials. RESULTS: Sixteen responses were collected of which 11 had previously participated in a transfusion randomized control trial. Various solutions were reported which were specific to the laboratory information system (LIS) and electronic medical record (EMR) combinations although solutions could be grouped into four categories which included the creation of a study product code in the LIS, preventing the transmission of data from the LIS to the EMR, utilizing specialized stickers and labels to conceal product containers and documents in the paper records, and modified bedside procedures and documentation. DISCUSSION: LIS and EMR combinations varied across sites, so it was not possible to determine combination-specific solutions. The study was able to highlight solutions that may be emphasized in future iterations of LIS and EMR software as well as procedural changes that may minimize the risk of unblinding.

Management strategies in persons with inherited haemophilia requiring antithrombotic therapy: A scoping review.

BACKGROUND: Thromboembolic events are increasingly reported in the aging haemophilia population. The purpose of this study was to understand current practices and identify knowledge and research gaps in the management of persons with haemophilia requiring antithrombotic therapy for cardiovascular disorders (CVD) or venous thromboembolism (VTE). METHODS: We searched MEDLINE, EMBASE and Scopus for studies reporting on more than two patients with inherited haemophilia A or B, without inhibitors, requiring antithrombotic therapy for CVD or VTE. Data were extracted by two independent reviewers and analysed using descriptive statistics and narrative synthesis. RESULTS: We included 32 studies reporting on 432 persons with haemophilia. Three themes described the observed practice variation: (1) Difficulty weighing competing bleeding and thrombotic risks; (2) Tensions in providing standards of care and minimizing bleeding risk; (3) Advocacy for individualized strategies and multidisciplinary care. Different management strategies were used to treat persons with haemophilia in the setting of thromboembolic events, such as avoiding or choosing lower intensity antithrombotic therapy, or procedural alternatives to antithrombotic therapy. Initiation or alteration in haemostatic therapies along with antithrombotic therapy were common strategies and reported in 30 studies. However, data on target factor levels and bleeding and thrombotic events were largely missing. DISCUSSION: Our scoping review highlights unmet needs in the management of an aging population of persons with haemophilia with increasing prevalence of CVD and VTE. Management is inconsistent and divergent from those of non-haemophilic patients. Prospective data are needed to inform optimal and evidence-based management strategies of CVD and VTE in persons with haemophilia.

Nonclinical factors affecting intraoperative red blood cell transfusion: a systematic review.

PURPOSE: There is significant variability in intraoperative red blood cell (RBC) transfusion practice. We aimed to use the theoretical domains framework (TDF) to categorize nonclinical and behavioural factors driving intraoperative RBC transfusion practice in a systematic review of the literature. SOURCE: We searched electronic databases from inception until August 2021 to identify studies evaluating nonclinical factors affecting intraoperative RBC transfusion. Using the Mixed Methods Appraisal Tool, we assessed the quality of included studies and identified relevant nonclinical factors, which were coded into TDF domains by two independent reviewers using NVivo (Lumivero, QSR International, Burlington, MA, USA). We identified common themes within domains and sorted domains based on the frequency of reported factors. PRINCIPAL FINDINGS: Our systematic review identified 18 studies: nine retrospective cohort studies, six cross-sectional surveys, and three before-and-after studies. Factors related to the social influences, behavioural regulation, environmental context/resources, and beliefs about consequences domains of the TDF were the most reported factors. Key factors underlying the observed variability in transfusion practice included the social effects of peers, patients, and institutional culture on decision-making (social influences), and characteristics of the practice environment including case volume, geographic location, and case start time (environmental context/resources). Studies reported variable beliefs about the consequences of both intraoperative transfusion and anemia (beliefs about consequences). Provider- and institutional-level audits, educational sessions, and increased communication between surgeons/anesthesiologists were identified as strategies to optimize intraoperative transfusion decision-making (behavioural regulation). CONCLUSION: Our systematic review has synthesized the literature on nonclinical and behavioural factors impacting intraoperative transfusion decision-making, categorized using the TDF. These findings can inform evidence-based interventions to reduce intraoperative RBC transfusion variability. STUDY REGISTRATION: Open Science Framework ( https://osf.io/pm8zs/?view_only=166299ed28964804b9360c429b1218c1 ; first posted, 3 August 2022).

RéSUMé: OBJECTIF: Il existe une variabilité importante dans les pratiques de transfusion peropératoire de culots sanguins. Nous avons cherché à utiliser le cadre des domaines théoriques (TDF, pour theoretical domains framework) pour catégoriser les facteurs non cliniques et comportementaux motivant les pratiques de transfusion peropératoire de culots sanguins dans une revue systématique de la littérature. SOURCES: Nous avons réalisé des recherches dans les bases de données électroniques de leur création jusqu'en août 2021 pour identifier les études évaluant les facteurs non cliniques affectant la transfusion peropératoire de culots sanguins. À l'aide de l'outil d'évaluation des méthodes mixtes, nous avons évalué la qualité des études incluses et identifié les facteurs non cliniques pertinents, qui ont été codés dans les domaines TDF par deux personnes les révisant de manière indépendante utilisant NVivo (Lumivero, QSR International, Burlington, MA, États-Unis). Nous avons identifié des thèmes communs au sein des domaines et trié les domaines en fonction de la fréquence des facteurs signalés. CONSTATATIONS PRINCIPALES: Notre revue systématique a identifié 18 études : neuf études de cohorte rétrospectives, six sondages transversaux et trois études avant-après. Les facteurs liés aux influences sociales, à la régulation comportementale, au contexte et aux ressources environnementaux et les croyances concernant les domaines de conséquences du TDF étaient les facteurs les plus rapportés. Les principaux facteurs sous-jacents à la variabilité observée dans la pratique transfusionnelle comprenaient les effets sociaux des pairs, de la patientèle et de la culture de l'établissement sur la prise de décision (influences sociales) et les caractéristiques de l'environnement de pratique, y compris le volume de cas, l'emplacement géographique et l'heure de début des cas (contexte/ressources environnementaux). Des études ont fait état de croyances variables sur les conséquences de la transfusion peropératoire et de l'anémie (croyances sur les conséquences). Des vérifications au niveau des prestataires et des établissements, des séances de formation et une communication accrue entre les chirurgien·nes et les anesthésiologistes ont été identifiées comme des stratégies pouvant optimiser la prise de décision transfusionnelle peropératoire (régulation comportementale). CONCLUSION: Notre revue systématique a synthétisé la littérature sur les facteurs non cliniques et comportementaux ayant une incidence sur la prise de décision transfusionnelle peropératoire, classés à l'aide du TDF. Ces résultats peuvent éclairer les interventions fondées sur des données probantes pour réduire la variabilité de transfusion peropératoire de culots sanguins. ENREGISTREMENT DE L'éTUDE: Open Science Framework ( https://osf.io/pm8zs/?view_only=166299ed28964804b9360c429b1218c1 ; soumis pour la première fois, 3 août 2022).

Patient perspectives on intraoperative blood transfusion: A qualitative interview study with perioperative patients.

BACKGROUND: While red blood cell (RBC) transfusions are frequently administered during surgery, little is known about patient perspectives regarding intraoperative transfusion. The aim of this study was to understand patient perspectives about intraoperative RBC transfusion and explore their willingness to engage in transfusion prevention strategies. STUDY DESIGN AND METHODS: This descriptive qualitative study used semi-structured patient interviews before and after surgery. Purposive sampling was used to select adult patients with varying perioperative courses, including having perioperative transfusion or postoperative anemia. Inductive and deductive thematic analyses were conducted to identify themes. RESULTS: Twenty patients (nine preoperative and 11 postoperative patients) were interviewed. The following themes were identified: Risk-benefit perception of transfusion, transfusion acceptance, trust, patient involvement in transfusion decisions, acceptance of transfusion prevention interventions, and communication. Patients perceived transfusions as low-risk compared to the surgery itself. Factors influencing transfusion acceptance included trust in the healthcare system and the perception of the treatability of transfusion-related complications. Some patients preferred to defer transfusion decision making to the perioperative team, citing trust in professional judgment and building a positive relationship with their surgeon. Others wished for their preferences to be incorporated into transfusion decisions. Some desired detailed blood consent conversations and most were willing to participate in strategies to reduce intraoperative transfusion. CONCLUSION: In our sample, patients consider intraoperative transfusions as low-risk high-reward interventions and trust the healthcare system and perioperative team to guide intraoperative transfusion decision making. However, preoperative transfusion consent discussions were recalled as being superficial and lacking nuance. Targeted strategies are required to improve blood consent discussions to better integrate patient preferences.

A Systematic Review and Meta-analysis of Randomized Controlled Trials Comparing Intraoperative Red Blood Cell Transfusion Strategies.

OBJECTIVE: The objective of this work was to carry out a meta-analysis of RCTs comparing intraoperative RBC transfusion strategies to determine their impact on postoperative morbidity, mortality, and blood product use. SUMMARY OF BACKGROUND DATA: RBC transfusions are common in surgery and associated with widespread variability despite adjustment for casemix. Evidence-based recommendations guiding RBC transfusion in the operative setting are limited. METHODS: The search strategy was adapted from a previous Cochrane Review. Electronic databases were searched from January 2016 to February 2021. Included studies from the previous Cochrane Review were considered for eligibility from before 2016. RCTs comparing intraoperative transfusion strategies were considered for inclusion. Co-primary outcomes were 30-day mortality and morbidity. Secondary outcomes included intraoperative and perioperative RBC transfusion. Meta-analysis was carried out using random-effects models. RESULTS: Fourteen trials (8641 patients) were included. One cardiac surgery trial accounted for 56% of patients. There was no difference in 30-day mortality [relative risk (RR) 0.96, 95% confidence interval (CI) 0.71-1.29] and pooled postoperative morbidity among the studied outcomes when comparing restrictive and liberal protocols. Two trials reported worse composite outcomes with restrictive triggers. Intraoperative (RR 0.53, 95% CI 0.43-0.64) and perioperative (RR 0.70, 95% CI 0.62-0.79) blood transfusions were significantly lower in the restrictive group compared to the liberal group. CONCLUSIONS: Intraoperative restrictive transfusion strategies decreased perioperative transfusions without added postoperative morbidity and mortality in 12/14 trials. Two trials reported worse outcomes. Given trial design and generalizability limitations, uncertainty remains regarding the safety of broad application of restrictive transfusion triggers in the operating room. Trials specifically designed to address intraoperative transfusions are urgently needed.

The association of venous thromboembolism with blood transfusion in kidney transplant patients.

BACKGROUND: Red blood cell transfusion (RBCT) is common after kidney transplantation and could have pro-thrombotic effects predisposing to venous thromboembolism (VTE). The risks for developing of VTE after RBCT in kidney transplant patients are unknown. STUDY DESIGN AND METHODS: This was a retrospective cohort study of adult kidney transplant recipients from 2002 to 2018. The exposure of interest was receipt of RBCT after transplant. Cox proportional hazards models were used to calculate hazard ratios (HR) for the outcomes of venous thromboembolism [VTE] (deep venous thrombosis [DVT] or pulmonary embolism [PE]) using RBCT as a time-varying, cumulative exposure. RESULTS: Out of 1258 kidney transplants recipients, 468 (37%) were transfused during the study period. Seventy-nine study participants (6.3%) developed VTE, 72 DVT (5.7%), and 22 PE (1.8%). For the receipt of 1, 2, 3-5, and >5 RBCT, compared to individuals never transfused, the number of events and adjusted HR (95%CI) for VTE were 6 (6.2%) HR 1.57 (0.69-3.58), 9 (7.6%) HR 2.54 (1.30-4.96), 15 (11.9%) HR 2.73 (1.38-5.41), and 23 (18.1%) HR 5.77 (2.99-11.14) respectively; for DVT, it was 6 (6.2%) HR 1.94 (0.84-4.48), 9 (7.6%) HR 2.92 (1.44-5.94), 14 (11.1%) HR 3.29 (1.63-6.65), and 21 (16.5%) HR 6.97 (3.53-13.76), respectively. For PE, among transfused individuals, there were 14 events (3.0%) and the HR was 2.40 (1.02-5.61). CONCLUSION: The risks for developing VTE, DVT, and PE were significantly increased in kidney transplant patients receiving RBCT after transplant. Receipt of RBCT should prompt considerations for judicious monitoring and assessment for thrombosis.

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.

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.

Red blood cell transfusion in myelodysplastic syndromes: A systematic review.

Patients with myelodysplastic syndrome (MDS) frequently receive red blood cell (RBC) transfusions for anaemia resulting from ineffective erythropoiesis. While RBC transfusions may rapidly increase haemoglobin values, their impact on clinical and health services outcomes in MDS patients has not previously been summarized. We conducted a systematic review of the literature to evaluate risks and benefits of RBC transfusions in MDS patients. We searched electronic databases (MEDLINE, Embase, CENTRAL, CINAHL) from inception through June 4, 2021 to identify studies reporting data on RBC transfusions in MDS patients. Full text publications that assessed RBC transfusions as an intervention and reported at least one clinical, laboratory, or healthcare outcome associated with transfusion were included. Study characteristics, transfusion information and transfusion-related outcomes were extracted and reported. We identified 1243 original studies, of which 38 met eligibility requirements and were included. Fourteen reported on survival following diagnosis of MDS, with the majority reporting poorer survival among patients receiving or requiring more frequent transfusions. Nine reported on transfusion-related iron overload and its complications. Other outcomes included rates of allo/autoimmunization and adverse transfusion reactions, and healthcare costs incurred by patients with a greater transfusion burden. Only two studies reported on symptom relief following transfusion. This review underscores transfusion dependence as a negative prognostic factor for MDS patients and highlights the paucity of evidence surrounding quality of life and symptom-related outcomes following RBC transfusions in this population. Further study of patient-important outcomes associated with transfusion in MDS patients is warranted to improve therapeutic recommendations and inform resource allocation.

Intraoperative Red Blood Cell Transfusion Decision-making: A Systematic Review of Guidelines.

OBJECTIVES: The objective of this work was to carry out a systematic review of clinical practice guidelines (CPGs) pertaining to intraoperative red blood cell (RBC) transfusions, in terms of indications, decision-making, and supporting evidence base. SUMMARY OF BACKGROUND DATA: RBC transfusions are common during surgery and there is evidence of wide variability in practice. METHODS: Major electronic databases (MEDLINE, EMBASE, and CINAHL), guideline clearinghouses and Google Scholar were systematically searched from inception to January 2019 for CPGs pertaining to indications for intraoperative RBC transfusion. Eligible guidelines were retrieved and their quality assessed using AGREE II. Relevant recommendations were abstracted and synthesized to allow for a comparison between guidelines. RESULTS: Ten guidelines published between 1992 and 2018 provided indications for intraoperative transfusions. No guideline addressed intraoperative transfusion decision-making as its primary focus. Six guidelines provided criteria for transfusion based on hemoglobin (range 6.0-10.0 g/dL) or hematocrit (<30%) triggers. In the absence of objective transfusion rules, CPGs recommended considering other parameters such as blood loss (n = 7), signs of end organ ischemia (n = 5), and hemodynamics (n = 4). Evidence supporting intraoperative recommendations was extrapolated primarily from the nonoperative setting. There was wide variability in the quality of included guidelines based on AGREE II scores. CONCLUSION: This review has identified several clinical practice guidelines providing recommendations for intraoperative transfusion. The existing guidelines were noted to be highly variable in their recommendations and to lack a sufficient evidence base from the intraoperative setting. This represents a major knowledge gap in the literature.

Red blood cell transfusion and associated outcomes in patients referred for palliative care: A retrospective cohort study.

BACKGROUND: We aim to describe the occurrence of red blood cell transfusion and associated predictive factors and outcomes among patients referred for palliative care. STUDY DESIGN AND METHODS: This retrospective cohort study used linked health administrative data of adults referred for palliative care at an academic hospital from 2014 to 2018. Multivariable regression models were employed to evaluate patient characteristics associated with transfusion and the relationship between transfusion status and location of death. Survival analyses were performed using log-rank tests and Cox proportional hazards modeling. RESULTS: Of 6980 evaluated patients, 885 (12.7%) were transfused following palliative care consultation. Covariate factors associated with transfusion included younger age, higher performance status, lower baseline hemoglobin, and a diagnosis of hematologic malignancy (OR = 2.97, 95% CI 2.20-4.01) or solid organ tumor (OR = 1.37, 95% CI 1.10-1.71) vs. noncancer diagnosis. Median survival from palliative care consultation was 19 (IQR 5-75) days; 83 (32-305) days in those transfused and 15 (4-57) days in the nontransfused group (p < .0001). Median survival following transfusion was 56 (19-200) days. Solid organ tumor diagnosis was independently associated with poor survival (HR = 1.7, 95% CI 1.39-2.09 vs. non-cancer diagnosis). Among individuals who survived ≥30 days, transfusion was associated with a higher likelihood of death in hospital (OR = 2.15, 95% CI 1.71-2.70 vs. home/subacute setting). DISCUSSION: Transfusions commonly occurred in patients receiving palliative care, associated with cancer diagnoses and favorable baseline prognostic factors. Poor survival following transfusion, particularly in solid organ tumor patients, and the twofold likelihood of death in hospital associated with this intervention have important implications in prescribing transfusion for this population.

Prophylactic tranexamic acid use in non-cardiac surgeries at high risk for transfusion.

BACKGROUND: Tranexamic acid (TXA) reduces transfusion in a wide range of surgical populations, although its real-world use in non-cardiac surgeries has not been well described. The objective of this study was to describe prophylactic TXA use in non-cardiac surgeries at high risk for transfusion. METHODS: This is a retrospective cohort study of all adult patients undergoing major non-cardiac surgery at ≥5% risk of perioperative transfusion at five Canadian hospitals between January 2014 and December 2016. Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database were linked to transfusion and laboratory databases. TXA use was ascertained electronically from The Ottawa Hospital Data Warehouse and via manual chart review for Winnipeg hospitals. For each surgery, we evaluated the percentage of patients who received TXA as well as the specifics of TXA dosing and administration. RESULTS: TXA use was evaluable in 14 300 patients. Overall, 17% of surgeries received TXA, ranging from 0% to 68% among individual surgeries. TXA use was more common in orthopaedic (n = 2043/4942; 41%) and spine surgeries (n = 239/1322; 18%) compared to other surgical domains (n = 109/8036; 1%). TXA was commonly administered as a bolus (n = 2097/2391; 88%). The median TXA dose was 1000 mg (IQR 1000-1000 mg). CONCLUSION: TXA is predominantly used in orthopaedic and spine surgeries, with little uptake in other non-cardiac surgeries at high risk for red blood cell transfusion. Further studies are needed to evaluate the effectiveness and safety of TXA and to understand the barriers to TXA administration in a broad range of non-cardiac surgeries.

Variation in prophylactic tranexamic acid administration among anesthesiologists and surgeons in orthopedic surgery: a retrospective cohort study.

PURPOSE: Tranexamic acid (TXA) reduces red blood cell transfusion in various orthopedic surgeries, yet the degree of practice variation in its use among anesthesiologists and surgeons has not been described. To target future knowledge transfer and implementation strategies, and to better understand determinants of variability in prophylactic TXA use, our primary objective was to evaluate the influence of surgical team members on the variability of prophylactic TXA administration. METHODS: This was a retrospective cohort study of all adult patients undergoing primary total hip arthroplasty (THA), hip fracture surgery, and spine fusion ± vertebrectomy at two Canadian hospitals between January 2014 and December 2016. We used Canadian Classification of Health Interventions procedure codes within the Discharge Abstract Database which we linked to the Ottawa Data Warehouse. We described the percentage of patients that received TXA by individual surgery, the specifics of TXA dosing, and estimated the effect of anesthesiologists and surgeons on prophylactic TXA using multivariable mixed-effects logistic regression analyses. RESULTS: In the 3,900 patients studied, TXA was most commonly used in primary THA (85%; n = 1,344/1,582), with lower use in hip fracture (23%; n = 342/1,506) and spine fusion surgery (23%; n = 186/812). The median [interquartile range] total TXA dose was 1,000 [1,000-1,000] mg, given as a bolus in 92% of cases. Anesthesiologists and surgeons added significant variability to the odds of receiving TXA in hip fracture surgery and spine fusion, but not primary THA. Most of the variability in TXA use was attributed to patient and other factors. CONCLUSION: We confirmed the routine use of TXA in primary THA, while observing lower utilization with more variability in hip fracture and spine fusion surgery. Further study is warranted to understand variations in use and the barriers to TXA implementation in a broader population of orthopedic surgical patients at high risk for transfusion.

RéSUMé: OBJECTIF: L'acide tranexamique (ATX) réduit la transfusion d'érythrocytes dans diverses chirurgies orthopédiques. Cependant, les variations de pratique quant à son utilisation parmi les anesthésiologistes et les chirurgiens n'ont pas été décrites. Afin de cibler les stratégies futures de transfert des connaissances et de mise en œuvre, et pour mieux comprendre les déterminants de la variabilité dans l'utilisation prophylactique d'ATX, notre objectif principal était d'évaluer l'influence des membres de l'équipe chirurgicale sur la variabilité de l'administration prophylactique d'ATX. MéTHODE: Il s'agissait d'une étude de cohorte rétrospective de tous les patients adultes subissant une arthroplastie totale primaire de la hanche (ATH), une chirurgie de fracture de la hanche et une fusion intervertébrale ± vertébrectomie dans deux hôpitaux canadiens entre janvier 2014 et décembre 2016. Nous avons utilisé les codes de procédure de la Classification canadienne des interventions en santé dans la Base de données sur les congés des patients, que nous avons liée à la banque de données d'Ottawa. Nous avons décrit le pourcentage de patients qui ont reçu de l'ATX par chirurgie individuelle, les détails du dosage de l'ATX, et avons estimé l'effet des anesthésiologistes et des chirurgiens sur l'ATX prophylactique en réalisant des analyses de régression logistique multivariées à effets mixtes. RéSULTATS: Parmi les 3900 patients étudiés, l'ATX était le plus fréquemment utilisé lors d'une ATH primaire (85 %; n = 1344/1582), avec une utilisation plus faible lors de chirurgie de fracture de la hanche (23 %; n = 342/1506) et de chirurgie de fusion intervertébrale (23 %; n = 186/812). La dose totale médiane [écart interquartile] d'ATX était de 1000 mg [1000 à 1000], administrés dans 92 % des cas sous forme de bolus. Les anesthésiologistes et les chirurgiens ont ajouté une variabilité significative aux probabilités de recevoir de l'ATX lors d'une chirurgie de fracture de la hanche et de fusion, mais pas lors d'ATH primaire. La majeure partie de la variabilité dans l'utilisation d'ATX était attribuable aux facteurs liés au patient et à d'autres facteurs. CONCLUSION: Nous avons confirmé l'utilisation de routine de l'ATX dans l'ATH primaire, tout en observant une utilisation moins répandue et plus variable lors de chirurgie de fracture de la hanche et de fusion intervertébrale. Une étude plus approfondie est nécessaire pour comprendre les variations d'utilisation et les obstacles à la mise en œuvre de l'ATX dans une population plus étendue de patients de chirurgie orthopédique à haut risque de transfusion.

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.

Volume-dependent effect of stored red blood cells: A secondary analysis of the Age of Blood Evaluation trial.

BACKGROUND: An increased risk of complications, including death, has been associated with stored red blood cell (RBC) units in observational studies but not in randomized trials. We aimed to evaluate for volume-dependent effects attributable to length of RBC storage in a secondary analysis of the Age of Blood Evaluation (ABLE) trial. STUDY DESIGN AND METHODS: In the 2510 critically ill adults from the ABLE trial randomized to receive RBC units stored not more than 7 days or the oldest compatible RBC units, we estimated the hazard ratio (HR) for death by intensive care unit (ICU) and hospital discharge and by days 28, 90, and 180, within subgroups defined by the number of RBC units received. Extended Cox proportional hazards regression was used to model the HR. RESULTS: A volume-dependent effect of storage age on survival was present for death by 90 and 180 days, but not earlier endpoints. The HR for death by 90 days was 0.55 (95% confidence interval [CI], 0.11-0.98, fresh vs standard) after transfusion of 6 RBC units but 1.45 (95% CI, 1.06-1.98) after transfusion of 1 RBC unit. CONCLUSION: In this exploratory analysis, volume-dependent effects related to RBC storage were documented in the ABLE trial. The harms associated with small volumes of fresh RBC units and large volumes of older RBC units should be further explored.

Trends and outcomes in multicomponent blood transfusion: an 11-year cohort study of a large multisite academic center.

BACKGROUND: Most studies reporting on blood component utilization overlook patients transfused with more than one type of blood product (multicomponent transfusion). These patients are of importance, as they are large consumers of blood products and likely have different characteristics and outcomes than nontransfused patients and patients transfused with only one blood component type. Our study aimed to determine the prevalence of multicomponent transfusion at a large multisite academic center, as well as the patient characteristics and outcomes associated with multicomponent transfusion. METHODS: A retrospective cohort study of transfused adult inpatients at the Ottawa Hospital between 2007 and 2017 was performed. Eligible transfusions were red blood cells (RBCs), platelets, plasma, cryoprecipitate, and/or fibrinogen concentrate. Descriptive analyses were done to determine multicomponent transfusion prevalence. Patient characteristics and outcomes associated with multicomponent transfusion were assessed using multivariable regressions. RESULTS: Of 55,719 adult transfused inpatient admissions, 25% received a multicomponent transfusion. Multicomponent transfusion prevalence was highest in hematology (51%), cardiac surgery (45%), and critical care (40%) patients. Multivariable regression analysis showed that compared to RBC-only transfusion, multicomponent transfusion was associated with increased odds of in-hospital mortality (odds ratio, 3.48; 95% confidence interval [CI], 3.26-3.73), greater odds of institutional discharge as opposed to discharge home (odds ratio, 1.22; 95% CI, 1.15-1.30), and a 1.58 time increase in duration of hospitalization (95% CI, 1.54-1.62). CONCLUSION: Multicomponent transfusion recipients make up a large proportion of transfused patients and have poorer outcomes. It is necessary to continue studying these patients, including outcomes and transfusion appropriateness, to inform best practices.

Exclusion criteria and adverse events in perioperative trials of tranexamic acid: a systematic review and meta-analysis.

BACKGROUND: Tranexamic acid (TXA) is an inexpensive therapy effective at minimizing perioperative blood loss and transfusion. However, it remains underutilized due to safety concerns. To date, no evidence-based guidelines exist identifying which patients should not receive TXA therapy. This study determined patient groups for whom safety information regarding TXA is lacking due to common exclusion from perioperative TXA trials. STUDY DESIGN AND METHODS: A systematic review searching the databases Medline, EMBASE, CENTRAL, and Clinicaltrials.gov was performed. Randomized controlled trials (RCTs) administering systemic TXA perioperatively to elective or emergent surgery patients were eligible. Our primary outcome was to describe exclusion criteria of RCTs, and the secondary outcome was TXA safety. A descriptive synthesis of exclusion criteria was performed, and TXA safety was assessed by meta-analysis. RESULTS: A total of 268 eligible RCTs were included. Meta-analysis showed that systemic TXA did not increase risk of adverse events compared to placebo or no intervention (relative risk, 1.05; 95% confidence interval, 0.99-1.12). Patient groups commonly excluded from perioperative TXA trials, and thus potentially lacking TXA safety data, were those with major comorbidities, a history of thromboembolism, medication use affecting coagulation, TXA allergy, and coagulopathy. Exclusion of patients with major comorbidities may not be necessary; we showed that the risk of adverse events was similar in studies that excluded patients with major comorbidities and those that did not. CONCLUSION: Sufficient evidence exists to develop perioperative guidelines for TXA use in many populations. Further studies evaluating perioperative TXA use in patients with a history of thromboembolism are warranted.

Trends in IVIG use at a tertiary care Canadian center and impact of provincial use mitigation strategies: 10-year retrospective study with interrupted time series analysis.

BACKGROUND: Intravenous immunoglobulin (IVIG) is a fractionated plasma product used to treat a range of autoimmune or inflammatory conditions, as well as immunodeficiency. Demand for this high-cost product is increasing worldwide. Understanding historical changes in IVIG use is important for inventory management and demand forecasting as well as for the development of initiatives aimed at optimizing blood product use. STUDY DESIGN AND METHODS: This was a 10-year retrospective cohort study of all patient encounters involving an IVIG transfusion from 2007 to 2016 at a four-site tertiary care hospital in Ontario, Canada. IVIG use was reported, including number of hospital encounters and amounts of IVIG prescribed. An interrupted time series analysis was performed to evaluate temporal changes in product use coinciding with the release of 2009-2010 provincial initiatives to optimize IVIG. RESULTS: A total of 1,658,159.50 g of IVIG was administered from 2007 to 2016. Total annual volume administered initially decreased after implementation of new policies (-2032 g/quarter). The number of IVIG patient encounters also decreased (-49.8 encounters/quarter) but was mirrored by an increase in the total volume administered per patient encounter (+0.88 g/quarter). Use increased 820 g/quarter from 2013 to 2016 but was 21% lower than projected before implementation of provincial policies. CONCLUSION: Trends in IVIG use show ongoing increases in the number of patients treated with the product. Development and implementation of provincial initiatives to optimize IVIG use coincided with significant short-term changes at a large tertiary care hospital. Novel initiatives aimed at dose minimization and prescription rationalization for this therapy are needed on local as well as larger scales.