A Significant Contribution of the Classical Pathway of Complement in SARS-CoV-2 Neutralization of Convalescent and Vaccinee Sera.

Although high titers of neutralizing Abs in human serum are associated with protection from reinfection by SARS-CoV-2, there is considerable heterogeneity in human serum-neutralizing Abs against SARS-CoV-2 during convalescence between individuals. Standard human serum live virus neutralization assays require inactivation of serum/plasma prior to testing. In this study, we report that the SARS-CoV-2 neutralization titers of human convalescent sera were relatively consistent across all disease states except for severe COVID-19, which yielded significantly higher neutralization titers. Furthermore, we show that heat inactivation of human serum significantly lowered neutralization activity in a live virus SARS-CoV-2 neutralization assay. Heat inactivation of human convalescent serum was shown to inactivate complement proteins, and the contribution of complement in SARS-CoV-2 neutralization was often >50% of the neutralizing activity of human sera without heat inactivation and could account for neutralizing activity when standard titers were zero after heat inactivation. This effect was also observed in COVID-19 vaccinees and could be abolished in individuals who were undergoing treatment with therapeutic anti-complement Abs. Complement activity was mainly dependent on the classical pathway with little contributions from mannose-binding lectin and alternative pathways. Our study demonstrates the importance of the complement pathway in significantly increasing viral neutralization activity against SARS-CoV-2 in spike seropositive individuals.

Re-evaluating treatment thresholds in patient blood management: Female patients experience more perioperative anaemia and higher transfusion rates in major elective surgery.

BACKGROUND AND OBJECTIVES: By optimizing erythropoiesis, patient blood management (PBM) programmes can reduce transfusions, lower mortality and provide cost-effective care. While definitions of anaemia have historically varied by sex, for the purposes of PBM, anaemia is defined as a haemoglobin <130 g/L. Our objective was to describe whether perioperative anaemia and transfusion rates in the PBM setting vary by sex. MATERIALS AND METHODS: We conducted a retrospective study of the Ontario Nurse Transfusion Coordinators Program (ONTraC) database from 2018 to 2022. ONTraC collects data from 25 Ontario hospitals which together account for >70% of Ontario's provincial blood use (~400,000 units per year). We collected data on patients undergoing elective isolated coronary artery bypass graft surgery (CABG), open heart valve replacement, CABG plus valve replacement, single-knee arthroplasty and single-hip arthroplasty. RESULTS: From 2018 to 2022, 17,700 patients were included in the ONTraC program; 47% were females (N = 8376). Across almost all years and procedures, females were found to have a significantly lower pre-operative, nadir and discharge haemoglobin as compared with males, irrespective of PBM interventions. Transfusion rates were significantly higher for females; this was most pronounced in cardiac surgery. CONCLUSION: Females experienced more perioperative anaemia and higher transfusion rates. Historic sex-specific definitions of anaemia may contribute to a greater tolerance of anaemia in females. Prioritizing females for multimodal PBM and consistently achieving a pre-operative haemoglobin >130 g/L may reduce the amount of red blood cell (RBC) transfusions that female patients receive.

The seasonal distribution of immune thrombotic thrombocytopenic purpura is influenced by geography: Epidemiologic findings from a multi-center analysis of 719 disease episodes.

Prior studies have suggested that immune thrombotic thrombocytopenic purpura (iTTP) may display seasonal variation; however, methodologic limitations and sample sizes have diminished the ability to perform a rigorous assessment. This 5-year retrospective study assessed the epidemiology of iTTP and determined whether it displays a seasonal pattern. Patients with both initial and relapsed iTTP (defined as a disintegrin and metalloprotease with thrombospondin type motifs 13 activity <10%) from 24 tertiary centers in Australia, Canada, France, Greece, Italy, Spain, and the US were included. Seasons were defined as: Northern Hemisphere-winter (December-February); spring (March-May); summer (June-August); autumn (September-November) and Southern Hemisphere-winter (June-August); spring (September-November); summer (December-February); autumn (March-May). Additional outcomes included the mean temperature in months with and without an iTTP episode at each site. A total of 583 patients experienced 719 iTTP episodes. The observed proportion of iTTP episodes during the winter was significantly greater than expected if equally distributed across seasons (28.5%, 205/719, 25.3%-31.9%; p = .03). Distance from the equator and mean temperature deviation both positively correlated with the proportion of iTTP episodes during winter. Acute iTTP episodes were associated with the winter season and colder temperatures, with a second peak during summer. Occurrence during winter was most pronounced at sites further from the equator and/or with greater annual temperature deviations. Understanding the etiologies underlying seasonal patterns of disease may assist in discovery and development of future preventative therapies and inform models for resource utilization.

Use of Intravenous Albumin: A Guideline From the International Collaboration for Transfusion Medicine Guidelines.

BACKGROUND: Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis. STUDY DESIGN AND METHODS: Cochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development, and Evaluation methodology. The guidelines were revised after public consultation. RESULTS: The panel made 14 recommendations on albumin use in adult critical care (three recommendations), pediatric critical care (one recommendation), neonatal critical care (two recommendations), cardiovascular surgery (two recommendations), kidney replacement therapy (one recommendation), and complications of cirrhosis (five recommendations). Of the 14 recommendations, two recommendations had moderate certainty of evidence, five recommendations had low certainty of evidence, and seven recommendations had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large-volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin commonly is transfused. INTERPRETATION: Currently, few evidence-based indications support the routine use of albumin in clinical practice to improve patient outcomes. These guidelines provide clinicians with actionable recommendations on the use of albumin.

Red blood cell transfusion: 2023 AABB international guidelines

Red blood cell transfusion is a common medical intervention with benefits and harms. To provide recommendations for use of red blood cell transfusion in adults and children. Standards for trustworthy guidelines were followed, including using Grading of Recommendations Assessment, Development and Evaluation methods, managing conflicts of interest, and making values and preferences explicit. Evidence from systematic reviews of randomized controlled trials was reviewed. For adults, 45 randomized controlled trials with 20 599 participants compared restrictive hemoglobin-based transfusion thresholds, typically 7 to 8 g/dL, with liberal transfusion thresholds of 9 to 10 g/dL. For pediatric patients, 7 randomized controlled trials with 2730 participants compared a variety of restrictive and liberal transfusion thresholds. For most patient populations, results provided moderate quality evidence that restrictive transfusion thresholds did not adversely affect patient-important outcomes. Recommendation 1: for hospitalized adult patients who are hemodynamically stable, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). In accordance with the restrictive strategy threshold used in most trials, clinicians may choose a threshold of 7.5 g/dL for patients undergoing cardiac surgery and 8 g/dL for those undergoing orthopedic surgery or those with preexisting cardiovascular disease. Recommendation 2: for hospitalized adult patients with hematologic and oncologic disorders, the panel suggests a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (conditional recommendations, low certainty evidence). Recommendation 3: for critically ill children and those at risk of critical illness who are hemodynamically stable and without a hemoglobinopathy, cyanotic cardiac condition, or severe hypoxemia, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). Recommendation 4: for hemodynamically stable children with congenital heart disease, the international panel suggests a transfusion threshold that is based on the cardiac abnormality and stage of surgical repair: 7 g/dL (biventricular repair), 9 g/dL (single-ventricle palliation), or 7 to 9 g/dL (uncorrected congenital heart disease) (conditional recommendation, low certainty evidence). It is good practice to consider overall clinical context and alternative therapies to transfusion when making transfusion decisions about an individual patient.

Patient blood management: recommendations rrom the 2018 Frankfurt consensus conference

What is the current evidence base for patient blood management (PBM) in adults, and what international clinical recommendations can be derived for preoperative anemia, red blood cell transfusion thresholds, and PBM implementation strategies? Diagnosis and management of preoperative anemia is crucial, and iron-deficient anemia should be treated with iron supplementation. Red blood cell transfusion thresholds for critically ill, clinically stable patients (hemoglobin concentration <7 g/dL), patients undergoing cardiac surgery (hemoglobin concentration <7.5 g/dL), patients with hip fractures and cardiovascular disease or risk factors (hemoglobin concentration <8 g/dL), and hemodynamically stable patients with acute gastrointestinal bleeding (hemoglobin concentration 7-8 g/dL) are relatively well defined, although the quality of evidence is moderate to low. Further high-quality research to support PBM is required for a range of clinical scenarios and implementation of PBM programs.