Transfusion-associated Circulatory Overload Research Articles

Classification of posttransfusion adverse events using a publicly available artificial intelligence system.

Correct classification of transfusion reactions is important not only for effective patient care and donor management but also for accurate tracking of events in hemovigilance systems. We compared the ability of a generative artificial intelligence (AI) system to correctly diagnose hypothetical clinical situations as transfusion reactions in comparison to previous studies reporting the accuracy of transfusion medicine (TM) specialists in assessing these cases. An AI system was requested to assess 36 case scenarios to provide a diagnosis, severity, and imputability of the transfusion reactions using the CDC National Healthcare Safety Network (NHSN) criteria. Responses were compared to an expert panel's classifications and to the published responses of a panel of TM specialists. Additionally, the AI's responses were compared to the TM specialists' prior attempts to use the TrDDx web-based algorithm for the five most challenging cases. The AI's classification accuracy varied widely depending on the NHSN category. The AI accurately classified all transfusion-associated circulatory overload and transfusion-related acute lung injury cases, exceeding TM specialists' assessments. Conversely, it did not correctly identify any cases in select NHSN categories such as DSTR. Overall accuracy among all diagnostic categories was 48.7% for AI responses versus 72.1% for prior TM specialist responses (p = 0.005). AI-generated responses included non-standard terminology, limited severity assessments, and no imputability determinations. A generative AI system may have a role in helping healthcare providers to consider transfusion reaction categories that might be missed, but caution is advised in applying the AI's output to transfusion reaction classification at present.

TRALI and TACO syndrome. Pathophysiology, diagnosis and treatment: a review

INTRODUCTION: TRALI (transfusion-related acute lung injury) and TACO (transfusion-associated circulatory overload) are severe post-transfusion reactions with high hospital mortality, uncertainty in pathophysiologic mechanisms and a blurred clinical presentation often lead to these conditions being underdiagnosed or missed by clinicians. OBJECTIVE: To analyze and summarize the current understanding of the pathophysiology, differential diagnosis and treatment of TRALI and TACO syndrome. To highlight the best approaches and current practices to improve treatment efficacy and awareness among specialists. MATERIALS AND METHODS: Articles in the following databases were analyzed: PubMed, eLibrary. The main inclusion criteria were: free access to the full content of the publications, compliance with the review topics concerning pathophysiology, diagnosis and treatment of TRALI- and TACO-syndrome. Exclusion criteria: abstracts, conference proceedings and editorial letters, as well as publications not indexed in specialized abstract databases. RESULTS: This article presents the main reference points, thanks to which clinicians can make a differential diagnosis among posttransfusion complications and select the optimal treatment. Since TACO is a simulated cardiogenic pulmonary edema as a result of altered cytokine profile, and TRALI-syndrome is a consequence of specific immunologic conflict between donor and recipient after hemotransfusion, these conditions should be differentiated in the inpatient setting, and specialists should use the full range of modern laboratory and instrumental methods. CONCLUSIONS: Despite a large number of studies, the pathophysiologic mechanisms of TRALI and TACO remain somewhat unclear, and current approaches to diagnosis and treatment are not effective. Therefore, the existing gaps in the diagnostics of posttransfusion reactions should be clarified in further studies, and clinicians should be extra vigilant in their choice of diagnosis.

Patient Blood Management: Moving Above and Beyond the Optimal Use of Blood!

Transfusion of blood components or products is among the most common procedures performed during a patient’s stay in the hospital. However, apart from being life-saving in exsanguination, blood transfusion is also associated with adverse events such as transfusion-transmitted infections, allergic reactions, transfusion-associated circulatory overload, transfusion-related acute lung injury, and transfusion-related immunomodulation with nosocomial infections and cancer recurrence. These potentially fatal complications have raised perennial concerns among healthcare professionals with regard to blood transfusion and patient outcomes. Thus, in the last few decades, the safety of the blood product has remained the key focus area for almost every stakeholder, whether end user or policy maker. Optimal use of blood is a globally recognized and recommended policy that ensures that the right amount and type of blood component is transfused to the right patient at the right time. Essentially, it focuses on improving the safety and effectiveness of the clinical transfusion process. However, with the evolving knowledge around transfusion science, increasing involvement of surgeons, anesthesiologists, and other specialists in transfusion offerings and proceedings, and the accumulating evidence on the fact that blood transfusion can, often, be more detrimental to a patient’s clinical status rather than benefiting it, has led to the endorsement and establishment of policy(ies) for optimal use of blood. Patient blood management (PBM), a concept coined and introduced almost two decades ago, encompasses, rather comprehensively, not just the policies and procedures of optimal use of blood and restricting transfusion to as minimum as possible but has a scope that spans much beyond that. PBM is driven and implemented through the three-pillar and nine-field matrix that incorporates the objectives of optimizing hematopoiesis, minimizing bleeding and blood loss, and harnessing and optimizing the physiological tolerance of anemia within the preoperative, intraoperative, and postoperative settings. PBM focuses on patient safety rather than product safety and, thus, ensures adopting a customized approach toward judicious and clinical use of the precious resource, blood. The principles and practices of PBM gained significant relevance and acceptability in the past few years, especially after the pandemic of COVID-19 when the World Health Organization issued a policy brief on its urgent implementation. Through this review article, we intend to establish not just the impact of PBM implementation towards improvement in patient outcomes but also the fact that the relevance and means of PBM extend far above and beyond just the optimal use of blood.

Massive Transfusion/Hemorrhage Protocols Versus Goal-Directed Bleeding Management: Science Gone Eerie?

Key questions in bleeding management are “Why does my patient bleed?” and “How to fix it?” To answer the first question, the high negative predictive value of viscoelastic testing can be used to identify coagulopathic bleeding. Accordingly, goal-directed bleeding management (GDBM) guided by viscoelastic testing has been shown to be an effective and essential part of the second pillar of patient blood management (PBM) with the aim to improve patients’ outcomes and safety. Patient’s medical and drug history – with a focus on medication with oral anticoagulants and antiplatelet drugs – are important in emergency, urgent, and elective surgery. Furthermore, risk scores have been developed and validated for traumatic and obstetric hemorrhage and can be helpful tools to predict severe hemorrhage and the need for massive transfusion. Acidosis, hypocalcemia, anemia, and hypothermia (“diamond of death in trauma”) are important basic conditions for hemostasis and good predictors of coagulopathy and should be closely monitored by blood gas analysis and corrected in bleeding patients. Earlier time to hemostasis was associated with decreased mortality in trauma studies. Therefore, GDBM aims to stop the bleeding as soon as possible and avoid the main killers in blood transfusion: Transfusion-associated circulatory overload, transfusion-related acute lung injury, transfusion-related immune modulation, and thrombosis. Thromboelastometry-guided bleeding management follows the concepts of Good Medical Practice and Precision Medicine. Here, rotational thromboelastometry (ROTEM)-guided bleeding management algorithms are using a stepwise approach based on the sequence “Treat first what kills first:” (1) Fibrinolysis management, (2) clot firmness management, (3) thrombin generation management, and (4) avoidance of hypercoagulability and thrombosis. Here, thromboelastometry can not only identify patients with hypercoagulability and increased risk of thrombosis but also ROTEM-guided bleeding management can avoid thromboembolic complications, too. This may support the idea of personalized antithrombotic therapy guided by viscoelastic testing in the postoperative period. Finally, PBM is not about blood transfusion: It is about patients’ outcomes. Accordingly, several meta-analyses based on more than 20 randomized controlled trials on the effect of viscoelastic testing-guided perioperative bleeding management did not only demonstrate a significant reduction in transfusion requirements but also a significant reduction in mortality and postoperative acute kidney injury. The reduction in postoperative acute kidney injury again has a significant impact on long-term survival. Accordingly, recent PBM guidelines recommend the implementation of viscoelastic testing-guided bleeding management algorithms with a 1B or 1A recommendation. This is also addressed in the World Health Organization policy brief about the urgent need to implement PBM in all member states in a timely manner. However, even if the number of national activities is increasing, there is still a long way to go.

Euvolemic automated transfusion to treat severe anemia in sickle cell disease patients at risk of circulatory overload.

Red blood cell (RBC) transfusion remains a major treatment for sickle cell disease (SCD). Patients with SCD have a high prevalence of renal impairment and cardiorespiratory disease, conferring risk of transfusion-associated circulatory overload (TACO). We describe an approach, titled euvolemic automated transfusion (EAT), to transfuse SCD patients with severe anemia who are at risk of TACO. In EAT, plasmapheresis is performed using donor RBCs, rather than albumin or plasma, as replacement fluid. Euvolemia is maintained. A retrospective analysis was conducted of patients with SCD who underwent EAT at our institution over a 10-year period, to evaluate the efficacy and safety of EAT. Eleven SCD patients underwent 109 EAT procedures (1-59 procedures per patient). The median age was 42 years (IQR = [30-49]) and 82% (n = 9) were female. Most (82%; n = 9) patients had severe chronic kidney disease and 55% (n = 6) had heart failure. One (9%) patient had a history of life-threatening TACO. Mean pre- and post-procedure Hct values were 19.8% (SD ± 1.6%) and 29.1% (SD ± 1.4%), respectively. The average Hct increment was 3.2% per RBC unit. Only two EAT-related complications were recorded during the 109 procedures: central line-associated infection and citrate toxicity (muscle cramping). EAT used an average of two RBC units less than that projected for standard automated RBC exchange. Our findings suggest that EAT is safe and effective to treat patients with SCD and severe anemia, who are at risk for TACO. EAT requires fewer RBC units compared to automated RBC exchange.

How Much Furosemide Should be Administered to Prevent Transfusion-Associated Circulatory Overload? Results of a Dose-Finding Study

BACKGROUND: Transfusion-associated circulatory overload (TACO) is a common but under-reported complication of transfusion therapy, and results in significant morbidity and mortality. Pre-transfusion furosemide has been proposed as a mitigating strategy but has not received widespread endorsement, in part due to uncertainty regarding safe and effective dosing. An observational study was therefore conducted with the goal of creating a reliable dose-response curve in patients at high risk of TACO, using the statistical technique of Multiple Comparisons Procedure with Modelling (MCP-MOD). METHODS: Eligible patients were identified by screening bolus intravenous (IV) furosemide orders at two large academic hospitals. Eligibility criteria were selected to mimic those of a planned randomized controlled trial (RCT) of pre-transfusion furosemide for the prevention of TACO. Inclusion criteria were inpatients 50 years of age or older. Exclusion criteria were active bleeding, hemodynamic instability, glomerular filtration rate (GFR) < 30mL/min or need for dialysis, diuretic therapy (other than furosemide) administered less than 24 hours, furosemide (either IV or PO) administered less than 12 hours, or exogenous albumin administered less than 8 hours prior to index furosemide therapy. The primary outcome measure was the total volume of urine output in the six hours following IV furosemide administration. MCP-MOD analysis was performed after every 50 patients and continued until a weight-adjusted dose-response curve could be established with 100 mL precision, using the following covariates: age, sex, mean arterial pressure (MAP), serum albumin, GFR and history of chronic furosemide use. RESULTS: A total of 149 participants (53 female and 96 male) were enrolled over 2 years. As too few patients received doses exceeding 0.6 mg/kg to allow for a precise dose-response curve, only 132 patients receiving weight-adjusted doses ranging from 0.1 to 0.6 mg/kg were included in the MCP-MOD analysis. The characteristics of these patients are shown in Table 1. The dose-response curve formula that was derived from these patients was: Urine Output at 6 hours (mL) = 717.21 + 191.33 ln(dose (mg)/weight (kg)) + 0.73 × Age (years) + 103.37 × Sex (M=1/F=0) + 1.63 × GFR (ml/min) + 5.45 × MAP (mmHg) - 9.56 × albumin (g/L) - 62.31 × chronic diuretic use (Y=1/N-0) The curve with accompanying 95% confidence intervals is shown in Figure 1 This formula suggests that in an 80 kg patient with a GFR of 75 mL/min, a MAP of 85 mmHg, albumin of 40 g/L and no history of chronic diuretic use, 10 mg of IV furosemide should produce a diuresis of approximately 600 mL, sufficient to prevent circulatory overload from the transfusion of 1 unit of RBCs. A dose of 20 mg would be required to achieve a similar diuresis in patients with either a MAP < 60 mmHg, or a combination of both a GFR < 45 mL/min and a history of chronic diuretic use. CONCLUSIONS: A statistically precise dose-response curve for IV furosemide is possible with the inclusion of relevant clinical covariates, and can be used to guide dosing decisions in patients at risk of transfusion-associated circulatory overload. This formula derived from this study will inform the dosing recommendations of a planned RCT: Transfusion-Associated Circulatory Overload: Best Eliminated by Lasix® (TACO-BEL).

CE: Recognizing Transfusion-Associated Circulatory Overload.

Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion-related deaths in the United States, accounting for more than 30% of fatalities reported to the Food and Drug Administration between 2016 and 2020. However, TACO is widely considered to be an underdiagnosed and underreported complication of blood transfusions, and its exact incidence is unknown. One of the reasons for this is a lack of recognition of TACO and its signs and symptoms, especially as the definition of TACO has been updated twice since 2018 without full dissemination to nurses, who are responsible for bedside care of patients during and following blood transfusions. This article seeks to bridge this gap by discussing the updated definitions and signs and symptoms of TACO, as well as the management of this treatable blood transfusion reaction.

82 Management of Very Severe Iron Deficiency Anemia: Is Transfusion Always Necessary?

Abstract Background Paediatric iron deficiency anemia (IDA) is a common condition in Canadian children; however, little is known about the natural history of extreme cases. This deficit makes it challenging to determine how to approach management when these patients present acutely to the emergency department (ED). Objectives To describe the clinical features and management of children presenting to the ED with very severe IDA with hemoglobin < 40 g/L. Design/Methods Retrospective chart reviews were performed for paediatric patients with IDA and hemoglobin < 40 g/L over a 5-year period (June 2017 – June 2022) at a Canadian tertiary care children’s hospital. Results Chart reviews were completed for 19 patients. The mean case rate was 3.1 patients annually (SD 2.14) with 11(58%) presenting in 2021–2022. Patients were young (median age 24 months; IQR 18–32) and predominantly female (79%). Nutritional deficiencies were the most common etiology (n=16, 84%). Median presenting hemoglobin was 25 g/L (IQR 22–36 g/L). The most common clinical features documented at presentation were pallor (n=19, 100%), tachycardia (n=17, 89%), and systolic ejection murmur (n=14, 74%). Thirteen (68%) patients had a ferritin measured in ED, 11(58%) had a chest x-ray, four (21%) had a lactate measured. One (5%) patient had an echocardiogram, and four (21%) had bedside cardiac ultrasounds documented. Eight (42%) patients with median hemoglobin 35 g/L (IQR 25–36 g/L) were managed without blood transfusion (PO iron only: n=3, 16%; IV iron only: n=5, 26%). Of the 11 (63%) patients who received blood, 2 (18%) had transfusion-related adverse events, with one patient undergoing intubation for transfusion-associated circulatory overload while admitted. All patients (100%) were initiated on oral iron supplementation. Ten patients (53%) received intravenous (IV) iron (dose 5–7 mg/kg) with one experiencing a mild reaction. Fifteen patients (79%) were hospitalized, with two (10%) admitted directly to the Paediatric Intensive Care Unit. Median duration of hospitalization was 5 days (IQR 2–9 days). Patients followed after transfusion-free management (n=5) demonstrated median hemoglobin increase of 21 g/L (IQR 20–32 g/L) within 12 days. No patient returned to the ED for anemia within 30 days. Conclusion Paediatric patients with very severe IDA do not always require transfusion. Some patients were effectively managed with IV iron alone. Investigation and management of these patients appears heterogenous. Given the risks of blood transfusion and the increased availability of IV iron, guidelines outlining evidence-based management of severe IDA are needed. These guidelines should promote optimization of iron therapy and guide judicious administration of blood transfusion.

Effect of fibrinogen concentrate on the initial fibrinogen level in trauma and postpartum hemorrhage.

Massive hemorrhage is a serious event that threatens the lives of patients. Fibrinogen concentrate (FC) can control bleeding without causing viral complications and without volume loading, which can happen in transfusion-associated circulatory overload and transfusion-associated acute lung injury. FC application is easy and does not require dissolution or extra devices. It is a cost-effective agent when considering the blood and products used in large quantities. A total of 67 postpartum hemorrhage (PPH) and trauma patients' medical records, who had ASA I-III classification (The American Society of Anesthesiologists classification of physical status), were obtained. Patients were divided into two groups (fibrinogen level ≤ 100 mg/dl and ≥ 101 mg/dl). The following information was obtained from patient files: demographic parameters, history of operations, and laboratory findings (i.e., complete blood counts, coagulation tests, and fibrinogen levels). Also, the duration of intensive care unit stays and mechanical ventilation application days, the administration of fresh frozen plasma (FFP), erythrocytes, platelets, and FC numbers, and tranexamic acid infusion were recorded. There was no mortality in PPH patients in either group (fibrinogen level ≤ 100 mg/dl and ≥ 101 mg/dl). The mortality rate in trauma patients was significantly higher in the group with fibrinogen levels ≤ 100. A total of 170 g of FC were given to PPH patients and 92 g to trauma patients. There were statistically significant differences between the preoperative PT (prothrombin time), postoperative APTT (activated partial thromboplastin time), postoperative PT, and postoperative INR (international normalized ratio) levels of the patients in the group with fibrinogen levels ≤ 100. Mortality rates were also significantly higher, and hospital stays significantly longer in trauma patients in the group with fibrinogen levels ≤ 100. Therapy may be considered during massive bleeding and transfusion, as it can help to increase fibrinogen levels quickly and efficiently. Compared with FFP, fibrinogen concentrate may have some advantages in reducing the risk of fluid overload. FFP contains a range of clotting factors, including fibrinogen. It also contains other proteins and fluids that can lead to fluid overload, especially when given in large volumes during massive transfusions.

Transfusion reaction: A blind spot in autopsy

Although blood transfusion is generally safe, there are adverse events with varying severity even that can lead to death including Acute Haemolytic Transfusion Reaction (AHTR), anaphylaxis, bacterial sepsis, Transfusion Related Acute Lung Injury (TRALI) and Transfusion Associated Circulatory Overload (TACO). Transfusion Associated Graft vs Host Disease (TAGVHD) is a delayed type of reaction that can lead to death. Ascertaining the cause of death is complicated in such situations and multidisciplinary investigations are needed.Serological investigations should be performed in the transfusion laboratory to detect haemolysis, immunological incompatibility, and bacterial contamination. In the postmortem examination AHTR can be diagnosed with serological investigations and presence of incompatible red cells can be identified in postmortem tissue samples by immune-histochemical methods. Detection of HLA antibodies in the respiratory tract tissues and intended donor investigations can confirm the diagnosis of TRALI. In a case of suspected bacterial contamination isolation of same organism in the postmortem blood and in the intended pack can conclude the diagnosis. In anaphylaxis, inflammation of the respiratory tract with eosinophilia can be seen and measuring the serum tryptase level is useful. In TAGVHD host tissue necrosis and lymphocyte infiltration are +seen and that can be confirmed by showing the DNA chimerism by PCR analysis.Further studies are recommended to establish protocols and guidelines for postmortem examination following a transfusion reaction.

Preventing transfusion-associated circulatory overload in acute care settings.

Transfusion-associated circulatory overload (TACO) is a potentially life-threatening complication that can occur with the transfusion of any blood component, and accounts for up to 24% of transfusion-associated patient fatalities. This article discusses how to develop evidence-based continuing education and guideline recommendations that will increase nursing staff awareness of TACO and guide nurses in prevention and prompt intervention.

Novel computational methods on electronic health record yields new estimates of transfusion-associated circulatory overload in populations enriched with high-risk patients.

Transfusion-associated circulatory overload (TACO) is a severe adverse reaction (AR) contributing to the leading cause of mortality associated with transfusions. As strategies to mitigate TACO have been increasingly adopted, an update of prevalence rates and risk factors associated with TACO using the growing sources of electronic health record (EHR) data can help understand transfusion safety. This retrospective study aimed to provide a timely and reproducible assessment of prevalence rates and risk factors associated with TACO. Novel natural language processing methods, now made publicly available on GitHub, were developed to extract ARs from 3178 transfusion reaction reports. Other patient-level data were extracted computationally from UCSF EHR between 2012 and 2022. The odds ratio estimates of risk factors were calculated using a multivariate logistic regression analysis with case-to-control matched on sex and age at a ratio of 1:5. A total of 56,208 patients received transfusions (total 573,533 units) at UCSF during the study period and 102 patients developed TACO. The prevalence of TACO was estimated to be 0.2% per patient (102/total 56,208). Patients with a history of coagulopathy (OR, 1.36; 95% CI, 1.04-1.79) and transplant (OR, 1.99; 95% CI, 1.48-2.68) were associated with increased odds of TACO. While TACO is a serious AR, events remained rare, even in populations enriched with high-risk patients. Novel computational methods can be used to find and continually surveil for transfusion ARs. Results suggest that patients with history or presence of coagulopathy and organ transplant should be carefully monitored to mitigate potential risks of TACO.

The effect of plasma transfusion in an experimental two-hit animal model of transfusion-associated circulatory overload with heart failure.

Transfusion-associated circulatory overload (TACO) is a leading cause of transfusion-related morbidity and mortality. TACO follows a two-hit pathophysiology, where comorbidities like cardiac or renal failure act as the first hit followed by blood transfusion as a second hit. Observational studies suggest that plasma transfusion is more likely to cause TACO than other blood products. We conducted a randomized animal study to gather evidence that plasma transfusion can induce TACO. As a first hit a large myocardial infarction was created in male Wistar rats. Then animals were randomized to receive 4 units of solvent/ detergent-treated pooled plasma (SDP), fresh frozen plasma (FFP), a colloid control (albumin 5%) or a crystalloid fluid control (Ringer's lactate) (n=10 per group). The primary outcome was the difference between pre- and post-transfusion left-ventricular end diastolic pressure (ΔLVEDP). Secondary outcomes were markers for acute lung injury; lung wet/dry weight ratio, PaO2/FiO2 ratio and pulmonary histological assessment. Pre-transfusion characteristics were similar between groups. ΔLVEDP increased significantly after transfusion with SDP (7.7 mmHg; 4.5-10.5) and albumin (13.0 mmHg; 6.5-15.2), but not after FFP (7.9 mmHg, 1.1; 11.3) compared to infusion with Ringer's lactate (0.6 mmHg; 0.4-2.2), p=0.007, p=0.0005 and p=0.14 respectively. There were no significant differences in ΔLVEDP between groups receiving SDP, FFP or albumin. There was no increase in acute lung injury in any group compared to other groups. Circulatory overload, measured as ΔLVEDP, was induced after transfusion of SDP or albumin, but not after infusion of Ringer's lactate. These results show that the effect of plasma transfusion on ΔLVEDP differs from fluid overload induced by crystalloid infusion. Colloid osmotic pressure may be an important component in the development of TACO and should be a target for future research.

Guideline on the investigation and management of acute transfusion reactions.

Guideline on the investigation and management of acute transfusion reactions.

Standardized reporting of pulmonary transfusion complications: Development of a model reporting form and flowchart.

Pulmonary complications of blood transfusion, including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and transfusion-associated dyspnea, are generally underdiagnosed and under-reported. The international TRALI and TACO definitions have recently been updated. Currently, no standardized pulmonary transfusion reaction reporting form exists and most of the hemovigilance forms have not yet incorporated the updated definitions. We developed a harmonized reporting form, aimed at improved data collection on pulmonary transfusion reactions for hemovigilance and research purposes by developing a standardized model reporting form and flowchart. Using a modified Delphi method among an international, multidisciplinary panel of 24 hemovigilance experts, detailed recommendations were developed for a standardized model reporting form for pulmonary complications of blood transfusion. Two Delphi rounds, including scoring systems, took place and several subsequent meetings were held to discuss issues and obtain consensus. Additionally, a flowchart was developed incorporating recently published redefinitions of pulmonary transfusion reactions. In total, 17 participants completed the first questionnaire (70.8% response rate) and 14 participants completed the second questionnaire (58.3% response rate). According to the results from the questionnaires, the standardized model reporting form was divided into various subcategories: general information, patient history and transfusion characteristics, reaction details, investigations, treatment and supportive care, narrative, and transfused product. In this article, we present the recommendations from a global group of experts in the hemovigilance field. The standardized model reporting form and flowchart provide an initiative that may improve data collected to address pulmonary transfusion reactions.

The transfusion-associated dyspnea prospective observation and laboratory assessment study: a protocol for investigating and disambiguating cardiopulmonary and high-grade febrile transfusion reactions in adults

Background: Cardiorespiratory transfusion reactions drive most transfusion-related morbidity and mortality. Transfusion-associated circulatory overload and transfusion-related acute lung injury have established causes, important impacts, mitigation options, and revised definitions, while non-conforming CRTRs fall into a category known as transfusion-associated dyspnea. Though procedures to investigate high-risk febrile transfusion reactions are typically rooted in detecting incompatibility or bacterial contamination, a common standard for examining CRTRs is lacking. CRTRs are further challenged by charting limitations, confounding (or enhanced susceptibility) by comorbidities, and/or overlapping insults. Deeper profiling of CRTRs could improve categorizations, reveal best-value diagnostics, and decipher the nature of (and/or minimize) reactions coded as TAD. Methods: The primary objective of this multi-center study is to reduce uncertainty in final conclusions drawn on CRTRs (cases), defined by dyspnea with objective disturbances and/or significant hemodynamic insults, with/without fever (±F). HRFTRs (controls) represent higher-grade F (T≥39°C or chills/rigors or lower-grade F (≥38°C by +Δ1°C) with non-respiratory effects). Patients (goal: 200) consent to additional sampling (≤24h post-TR) to identify contributing factors in case/control presentations, and in diagnostic groups (TRALI, TACO±F, TAD). Mechanistic axes of interest are cardiorenal, hemolytic, leukoagglutinating, biolipid, vasoactive, and inflammatory. Secondary goals include elucidation of real-life “insult-multiplicity” in CRTRs, tests of greatest yield, and distinguishing features in TRALI/TACO/TAD. Conclusions: A deep systematic CRTR probe may not only reduce diagnostic uncertainty but frame biomarker performance and pathologic signatures in definition-specific CRTRs. The re-classifiability or biology of TAD may be better understood. High-quality, mechanistic, true-to-quantity hemovigilance better exposes burdens and management options. Trial Registration: The trial is registered with ClinicalTrials.gov. with registry number NCT04267029.

The impact of revised definitions for transfusion-associated circulatory overload and transfusion-related acute lung injury on haemovigilance reporting.

Transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) are serious adverse transfusion reactions. Standardized surveillance definitions are important to ensure consistent reporting of cases. Recently, revised definitions have been developed for TACO and TRALI, the latter of which has not yet been widely implemented. This study aimed to assess the impact of the new TACO and TRALI definitions on haemovigilance reporting. The Australian Red Cross Lifeblood Adverse Transfusion Reaction database was accessed to identify all cases of suspected or confirmed TACO and TRALI referred from 1 July 2015 to 30 June 2019. Cases were assessed against both the former and new definitions and the results were compared. A total of 73 cases were assessed. There were 48 TACO cases identified. Only 26 of 48 cases strictly met the former 2011 International Society of Blood Transfusion (ISBT) definition of TACO; 6 cases did not meet the definition and 16 cases lacked sufficient clinical details. In comparison, 46 cases met the revised 2018 ISBT definition, with only 2 cases having insufficient details. There were 24 cases of TRALI according to the existing 2004 Canadian Consensus Conference (CCC) definition compared with 25 cases according to the proposed 2019 revised definition. The revised TACO definition captured more cases than the former definition. No significant differences were observed in the number of TRALI cases under the proposed new definition. This is the first study to provide validation data for the revised TRALI definition.

Can volume-reduced plasma products prevent transfusion-associated circulatory overload in a two-hit animal model?

Transfusion-associated circulatory overload (TACO) is a pulmonary transfusion complication and a leading cause of transfusion-related morbidity and mortality. Volume overload and rising hydrostatic pressure as a consequence of transfusion are seen as the central pathway leading to TACO. A possible preventative measure for TACO could be the use of low-volume blood products like volume-reduced lyophilized plasma. We hypothesize that volume-reduced lyophilized plasma decreases circulatory overload leading to a reduced pulmonary capillary pressure and can therefore be an effective strategy to prevent TACO. A validated two-hit animal model in rats with heart failure was used. Animals were randomized to receive 4 units of either solvent-detergent pooled plasma (SDP) as control, standard volume lyophilized plasma (LP-S) or hyperoncotic volume-reduced lyophilized plasma (LP-VR). The primary outcome was the difference between pre-transfusion and post-transfusion left ventricular end-diastolic pressure (ΔLVEDP). Secondary outcomes included markers for acute lung injury. LVEDP increased in all randomization groups following transfusion. The greatest elevation was seen in the group receiving LP-VR (+11.9 mmHg [5.9-15.6]), but there were no significant differences when compared to groups receiving either LP-S (+6.3 mmHg [2.9-13.4], p=0.29) or SDP (+7.7 mmHg [4.5-10.5], p=0.55). There were no significant differences in markers for acute lung injury, such as pulmonary wet/dry weight ratios, lung histopathology scores or PaO2 /FiO2 ratio between the three groups. Transfusion with hyperoncotic volume-reduced plasma did not attenuate circulatory overload compared to standard volume plasma and was therefore not an effective preventative strategy for TACO in this rat model.

Convalescent Plasma as Adjunctive Therapy for Hospitalized Patients with COVID-19: The Co-CLARITY Trial

Background and Objective. Convalescent plasma therapy (CPT) may reduce the risk of disease progression among patients with COVID-19. This study was undertaken to evaluate the efficacy and safety of CPT in preventing ICU admission among hospitalized COVID-19 patients.Methods. In this open-label randomized controlled trial, we randomly assigned hospitalized adult patients withCOVID-19 in a 1:1 ratio to receive convalescent plasma as an adjunct to standard of care or standard of care alone. The primary endpoint was ICU admission within first 28 days of enrolment. Primary safety endpoints include rapid deterioration of respiratory or clinical status within four hours of convalescent plasma transfusion and cumulative incidence of serious adverse events during the study period including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), severe allergic reactions, and transfusion-related infections.Results. A total of 22 patients were assigned to receive convalescent plasma as an adjunct to standard of care and 22 to receive standard of care alone. The median time from onset of COVID-19 symptoms to study enrolment was eight days (IQR, 4 to 10). Two patients (9.1%) in the CPT group and one patient (4.5%) in the control group were admitted to the ICU. The primary outcome measure, ICU admission, was not different between the two groups (q-value >0.9). No patient who received convalescent plasma had rapid deterioration of respiratory/clinical status within four hours of transfusion and none developed TRALI, TACO, anaphylaxis, severe allergic reactions, or transfusion-related infections. There was also no significant difference in the secondary outcomes of 28-day mortality (two patients in the CPT group and none in the control group, q-value >0.90), dialysis-free days, vasopressor-free days, and ICU-free days. Conclusions. Among hospitalized COVID-19 patients, no significant differences were observed in the need forICU admission between patients given CPT as adjunct to standard of care and those who received standard ofcare alone. Interpretation is limited by early termination of the trial which may have been underpowered todetect a clinically important difference.

The role of point of care thromboelastography (TEG) and thromboelastometry (ROTEM) in management of Primary postpartum haemorrhage: A meta-analysis and systematic review.

The utility of instantaneous evaluation of coagulation during primary postpartum haemorrhage (PPH) is paramount in the context of empirical blood product transfusion-related risk of dilutional and consumptive coagulopathy and circulatory overload. A profound screening of electronic databases till August 15, 2022 was carried out after being enlisted in PROSPERO (CRD42021275514). Randomized control studies, comparative cohort studies, and cross-sectional studies comparing point-of-care viscoelastic test guided blood product transfusion with empirical transfusion in patients with PPH were included. We retrieved five studies, with a total of 1914 parturient with PPH. Patients receiving transfusion based upon point of care viscoelastic tests had lesser risk of having emergency hysterectomy (Odds ratio (OR) = 0.55, 95% CI 0.32-0.95, I2 = 7%), transfusion-associated circulatory overload (TACO) (OR = 0.03, 95% CI 0.00-0.50), reduced transfusion of fresh frozen plasma (OR = 0.07, 95% CI 0.04-0.14, I2 = 89%), platelets (OR = 0.51, 95% CI 0.28-0.91, I2 = 89%), packed red blood cell transfusion (OR = 0.70, 95% CI 0.55-0.88, I2 = 89%), and had better cost-effective treatment [Mean difference (MD) = -357.5, 95% CI - 567.75 to -147.25, I2 = 93%] than patient received empirical transfusion. However, there was no significant difference in the requirement of ICU admissions (OR = 0.77, 95% CI = 0.46-1.29, I2 = 82%). No mortality was detected across the studies. Point of care viscoelastic assessment guided transfusion in PPH confederates with reduced morbidity. Nevertheless, more studies on the triggering values for transfusion, long-term survival, and cost-benefit in patients with PPH are warranted to establish its utility.