Proteomic Characterization of Transfusable Blood Components: Fresh Frozen Plasma, Cryoprecipitate, and Derived Extracellular Vesicles via Data-Independent Mass Spectrometry.

Extracellular vesicles (EVs) are a heterogeneous collection of particles that play a crucial role in cell-to-cell communication, primarily due to their ability to transport molecules, such as proteins. Thus, profiling EV-associated proteins offers insight into their biological effects. EVs can be isolated from various biological fluids, including donor blood components such as cryoprecipitate and fresh frozen plasma (FFP).

Effects of red blood cell transfusion on patients undergoing cardiac surgery in Queensland - a retrospective cohort study.

Background: Packed red blood cell (pRBC) transfusion is a relatively safe and mainstay treatment commonly used in cardiac surgical patients. However, there is limited evidence on clinical effects of transfusing blood nearing end-of shelf life that has undergone biochemical changes during storage.

Objective: To investigate evidence of associations between morbidity/mortality and transfusion of blood near end of shelf-life (> 35 days) in cardiac surgical patients.

Extracellular vesicles in fresh frozen plasma and cryoprecipitate: Impact on in vitro endothelial cell viability.

Background: Transfusion-related acute lung injury (TRALI) remains a major contributor to transfusion-associated mortality. While the pathogenesis of TRALI remains unclear, there is evidence of a role for blood components. We therefore investigated the potential effects of fresh frozen plasma (FFP), cryoprecipitate, and extracellular vesicles (EVs) derived from these blood components, on the viability of human lung microvascular endothelial cells (HLMVECs) in vitro.

Intraoperative cell salvage: The impact on immune cell numbers.

Background: Patient outcomes are influenced by many confounding factors peri-operatively, including the type of surgery, anaesthesia, transfusion, and immune competence. We have previously demonstrated (in-vitro) that compared to allogeneic blood transfusion (ABT), intraoperative cell salvage (ICS) improves immune competence. The peri-operative immune response is complex.

Investigation of the effect of pre-analytical factors on particle concentration and size in cryoprecipitate using nanoparticle tracking analysis.

Background: Cryoprecipitate is used primarily to replenish fibrinogen levels in patients. Little is known about the presence of micro- or nano-sized particles in cryoprecipitate. Therefore, we aimed to quantify these particles and investigate some pre-analytical considerations.

Next generation sequencing to identify iron status and individualise blood donors' experience.

Background: Young adults form the majority of first-time blood donors to Australian Red Cross Lifeblood. However, these donors pose unique challenges for donor safety. Young blood donors, who are still undergoing neurological and physical development, have been found to have lower iron stores, and have higher risks of iron deficiency anaemia when compared to older adults and non-donors.

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

Background And Objectives: 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.

Transfusion-related acute lung injury (TRALI): a retrospective review of reported cases in Queensland, Australia over 20 years.

Background: Transfusion-related acute lung injury (TRALI) is a rare but potentially fatal transfusion reaction. An effective haemovigilance programme is important in implementing successful and targeted risk reduction strategies. We aim to provide a summary of TRALI cases referred for investigation in Queensland (QLD) Australia from 1999 to 2019, describing the epidemiological and laboratory features of local TRALI cases.

Human neutrophil antigen 3 genotype impacts neutrophil-mediated endothelial cell cytotoxicity in a two-event model of TRALI.

Background: Antibodies against human neutrophil antigen (HNA)-3a are associated with severe cases of transfusion-related acute lung injury (TRALI). The HNA-3 system is located on choline transporter-like 2 (CTL-2) protein. CTL-2 is encoded by the gene SLC44A2 and a single-nucleotide polymorphism c.

Recovery of organ-specific tissue oxygen delivery at restrictive transfusion thresholds after fluid treatment in ovine haemorrhagic shock.

Background: Fluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured.

Transfusion-related acute lung injury (TRALI): Potential pathways of development, strategies for prevention and treatment, and future research directions.

Transfusion-related acute lung injury (TRALI) can occur during or after a transfusion, and remains a leading cause of transfusion-associated morbidity and mortality. TRALI is caused by the transfusion of either anti-leukocyte antibodies or biological response modifiers (BRMs). Experimental evidence suggests at least six different pathways that antibody-mediated TRALI might follow: (i) two hit neutrophil activation; (ii) monocyte and neutrophil dependent; (iii) endothelial cell, neutrophil Fc receptor, platelet and neutrophil extracellular trap dependent; (iv) direct monocyte activation; (v) direct endothelial cell activation; and (vi) endothelial cell, complement and monocyte dependent.

Psychological impact of the COVID-19 pandemic on young professionals in blood banks and transfusion services: A global cross-sectional survey.

Background And Objectives: The COVID-19 pandemic brought about changes to daily life as measures to contain the spread of the virus increased across the world. The aim of this survey was to assess the psychological impact of the pandemic on young professionals (YPs) in transfusion medicine.

Materials And Methods: A cross-sectional web-based survey was distributed electronically to ISBT members inviting YPs (≤40 years) to participate.

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death.

Background: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient.

An Ovine Model of Hemorrhagic Shock and Resuscitation, to Assess Recovery of Tissue Oxygen Delivery and Oxygen Debt, and Inform Patient Blood Management.

Background: Aggressive fluid or blood component transfusion for severe hemorrhagic shock may restore macrocirculatory parameters, but not always improve microcirculatory perfusion and tissue oxygen delivery. We established an ovine model of hemorrhagic shock to systematically assess tissue oxygen delivery and repayment of oxygen debt; appropriate outcomes to guide Patient Blood Management.

Methods: Female Dorset-cross sheep were anesthetized, intubated, and subjected to comprehensive macrohemodynamic, regional tissue oxygen saturation (StO2), sublingual capillary imaging, and arterial lactate monitoring confirmed by invasive organ-specific microvascular perfusion, oxygen pressure, and lactate/pyruvate levels in brain, kidney, liver, and skeletal muscle.

Ovine red cell concentrates for transfusion research - is the storage lesion comparable to human red cell concentrates?

Background And Objectives: Sheep are increasingly being used as a large in vivo animal model of blood transfusion because they provide several advantages over small animals. Understanding the effects of storage duration on ovine (ov) red cell concentrates (RCCs) and how these changes compare with stored human (hu) RCCs is necessary to facilitate clinical translation of research findings.

Materials And Methods: OvRCCs (n = 5) collected and processed in standard human blood collection packs, and equivalent huRCCs provided by Australian Red Cross Lifeblood (n = 5), were stored at 2-6°C for 42 days, with samples collected weekly.

Intraoperative Cell Salvage as an Alternative to Allogeneic (Donated) Blood Transfusion: A Prospective Observational Evaluation of the Immune Response Profile.

Allogeneic blood transfusion (ABT) is associated with transfusion-related immune modulation (TRIM) and subsequent poorer patient outcomes including perioperative infection, multiple organ failure, and mortality. The precise mechanism(s) underlying TRIM remain largely unknown. During intraoperative cell salvage (ICS) a patient's own (autologous) blood is collected, anticoagulated, processed, and reinfused.

Development and validation of ELISAs for the quantitation of interleukin (IL)-1β, IL-6, IL-8 and IL-10 in ovine plasma.

There is growing evidence that inflammation underpins many common diseases. Inflammatory/immunomodulatory/immune mediators, such as cytokines, are key modulators of inflammation and mediate both immune cell recruitment and complex intracellular signalling pathways. Ovine models of disease are increasingly utilized in pre-clinical research, however existing methods for measuring cytokine levels are limited.

Coronary artery bypass grafting is associated with immunoparalysis of monocytes and dendritic cells.

Coronary artery bypass grafting (CABG) triggers a systemic inflammatory response that may contribute to adverse outcomes. Dendritic cells (DC) and monocytes are immunoregulatory cells potentially affected by CABG, contributing to an altered immune state. This study investigated changes in DC and monocyte responses in CABG patients at 5 time-points: admission, peri-operative, ICU, day 3 and day 5.

Fresh frozen plasma and platelet concentrate storage duration not associated with in hospital mortality risk.

Background And Objectives: To date, the effects of FFP and PC storage duration on mortality have only been studied in a few studies in limited patient subpopulations. The aim of the current study was to determine whether FFP and PC storage duration is associated with increased in hospital mortality risk across cardiac surgery, acute medicine, ICU and orthopaedic surgery patients.

Materials And Methods: Two-stage individual patient data meta-analyses were performed to determine the effects of FFP and PC storage duration on in hospital mortality.

Pre-clinical study protocol: Blood transfusion in endotoxaemic shock.

The Surviving Sepsis Campaign (SCC) and the American College of Critical Care Medicine (ACCM) guidelines recommend blood transfusion in sepsis when the haemoglobin concentration drops below 7.0 g/dL and 10.0 g/dL respectively, while the World Health Organisation (WHO) guideline recommends transfusion in septic shock 'if intravenous (IV) fluids do not maintain adequate circulation', as a supportive measure of last resort.

Fluid resuscitation with 0.9% saline alters haemostasis in an ovine model of endotoxemic shock.

Introduction: Fluid resuscitation is a cornerstone of severe sepsis management, however there are many uncertainties surrounding the type and volume of fluid that is administered. The entire spectrum of coagulopathies can be seen in sepsis, from asymptomatic aberrations to fulminant disseminated intravascular coagulation (DIC). The aim of this study was to determine if fluid resuscitation with saline contributes to the haemostatic derangements in an ovine model of endotoxemic shock.

Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock.

Background: Sepsis is a multi-system syndrome that remains the leading cause of mortality and critical illness worldwide, with hemodynamic support being one of the cornerstones of the acute management of sepsis. We used an ovine model of endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung inflammation and injury in acute respiratory distress syndrome, which is a common complication of sepsis, and investigated the potential role of matrix metalloproteinases in this process.

Unintended Consequences: Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia.

Rationale: Fluid resuscitation is widely considered a life-saving intervention in septic shock; however, recent evidence has brought both its safety and efficacy in sepsis into question.

Objectives: In this study, we sought to compare fluid resuscitation with vasopressors with the use of vasopressors alone in a hyperdynamic model of ovine endotoxemia.

Methods: Endotoxemic shock was induced in 16 sheep, after which they received fluid resuscitation with 40 ml/kg of 0.