Respiratory burst function of ovine neutrophils

Background: Respiratory burst function resulting in the release of reactive oxygen species such as superoxide anion (O(2)(-)) from neutrophils is one of the key mechanisms of the innate immune system, and maladaptive control of this mechanism is thought to play a pivotal role in the development of pathologies such as acute lung injury and sepsis. Ovine models of these pathologies are limited by the poor understanding of ovine neutrophil respiratory burst function

The impact of acute lung injury, ECMO and transfusion on oxidative stress and plasma selenium levels in an ovine model

The purpose of this study was to determine the effects of smoke induced acute lung. injury (S-ALI), extracorporeal membrane oxygenation (ECMO) and transfusion on oxidative stress and plasma selenium levels. Forty ewes were divided into (i) healthy control (n = 4), (ii) S-ALI control (n = 7), (iii) ECMO control (n = 7), (iv) S-ALI + ECMO (n = 8) and (v) S-ALI + ECM + packed red blood cell (PRBC) transfusion (n = 14). Plasma thiobarbituric acid reactive substances (TBARS), selenium and glutathione peroxidase (GPx) activity were analysed at baseline, after smoke injury (or sham) and 0.25, 1, 2, 6, 7, 12 and 24 h after initiation of ECMO. Peak TBARS levels were similar across all groups. Plasma selenium decreased by 54% in S-ALI sheep (1.36 +/- 0.20 to 0.63 +/- 0.27 mu mol/L, p < 0.0001), and 72% in sheep with S-ALI + ECMO at 24 h (1.36 +/- 0.20 to 0.38 +/- 0.19, p < 0.0001). PRBC transfusion had no effect on TBARS, selenium levels or glutathione peroxidase activity in plasma. While ECMO independently increased TBARS in healthy sheep to levels which were similar to the S-ALI control, the addition of ECMO after S-ALI caused a negligible increase in TBARS. This suggests that the initial lung injury was the predominant feature in the TBARS response. In contrast, the addition of ECM in S-ALI sheep exacerbated reductions in plasma selenium beyond that of S-ALI or ECM alone. Clinical studies are needed to confirm the extent and duration of selenium loss associated with ECMO. Crown Copyright (C) 2015 Published by Elsevier GmbH. All rights reserved

Developments in the detection of HNA and HLA antibodies

No abstract available

Non-antibody mediated transfusion-related acute lung injury an enigma

In 20% to 28% of transfusion-related acute lung injury (TRALI) cases, no leucocyte antibodies have been detected and such cases are described as non-antibody mediated TRALI. In the other 72% to 80% of TRALI cases, leucocyte antibodies are hypothesized to be the “second hit” that precipitates acute lung injury (ALI) in a sick patient. There is a substantial body of evidence demonstrating an association between TRALI and antibodies to human neutrophil antigens (HNA), human leukocyte antigens (HLA) class I and II. Therefore, one of the most widely used TRALI mitigation strategies has been to reduce/avoid use of blood components that contain or are more likely to contain these antibodies. Despite the success of these risk reduction strategies, hemovigilance data show that TRALI remains a serious and sometimes fatal complication of transfusion. This is possibly because the current TRALI risk-reduction strategies all focus on antibody mediated TRALI but do not address non-antibody mediated TRALI. This review discusses the available evidence on non-antibody mediated TRALI

Antioxidant trace element reduction in an in vitro cardiopulmonary bypass circuit

Many complications occurring after cardiac surgery are attributed to an acute increase in reactive oxygen and reactive nitrogen species, which under normal conditions are balanced by the antioxidant response. Two key enzymes of the antioxidant response, glutathione peroxidase (GPx) and superoxide dismutase (SOD), rely on trace elements for normal function. It was hypothesized that circulation of blood through the cardiopulmonary bypass (CPB) circuit would 1) reduce trace element levels and antioxidant function, 2) increase oxidative stress, and that 3) prepriming circuits with albumin would ameliorate trace element loss. This hypothesis was investigated by circulating fresh human whole blood in an in vitro CPB circuit. Plasma selenium, copper, and zinc levels were measured, as were SOD and GPx and oxidative stress by thiobarbituric acid reactive substances (TBARS). In spite of significant decreases in copper and zinc levels, SOD levels increased with time. Significant decreases in selenium were associated with a trend to increase TBARS but no change in GPx. Prepriming with albumin provided no benefit as it did not reduce trace element loss nor alter levels of oxidative stress. This study confirms that CPB circuits cause significant depletion of trace elements (selenium, copper, and zinc) necessary to maintain redox homeostasis. The loss of trace elements is a potential contributor to cardiac surgical morbidities, and further studies in the cardiac patient population are needed to investigate this

Blood management in hip fractures; are we leaving it too late? A retrospective observational study

Abstract Background Anaemia in hip fracture patients has been associated with increased risk of allogenic blood transfusion (ABT), poorer functional outcomes and increased mortality. Few studies have reported the prevalence of anaemia on admission or its progression prior to surgery in this cohort. We aimed to measure the prevalence of anaemia on admission in older persons who sustain a hip fracture, identify if anaemia develops or progresses prior to surgery, and to report associations with outcome. Methods A retrospective, observational study was undertaken in a regional hospital. All patients aged 60 and over, admitted with a primary hip fracture resulting from a simple fall, in the 12 months of 2014 were included. The World Health Organization (WHO) definition of anaemia was used. Pathology databases and clinical records were reviewed to collect data. Repeated measures ANOVA’s were used to quantify the progression of anaemia prior to surgery, and Chi square test were used to report associations with outcome variables. Results Two hundred sixty-one patients were identified, median age was 81 years. There were twice as many females as males and just over half the sample had extracapsular fractures. Anaemia was present on admission in 45% (n = 117), highest incidence of anaemia occurred in males 52.0% (n = 39), extracapsular fractures 41.9% (n = 78) and those aged over 80 years 49.7% (n = 91). Progression of anaemia prior to surgery was significant in all groups (p < 0.05), with the greatest reduction seen in extracapsular fractures. Pre-surgery reduction in Hb was recorded in 82.3% of patients between admission and day 1, and in 71.4% between admission and day 2. There was significant association between anaemia on admission and PRBC transfusion (p < 0.05), in hospital mortality (p < 0.05) however no association with the use of antiplatelet or anticoagulant medication, nor LOS. Conclusions The findings demonstrate that pre-surgical anaemia in older hip fracture patients is associated with a PRBC transfusion and increased hospital mortality. Importantly, it also identified that patients continue to bleed after admission, leading to the development of or worsening anaemia. Thus, identification anaemia in the pre-surgical period provides an opportunity for treatment to avoid transfusions and improve patient outcomes

A retrospective explanatory case study of the implementation of a bleeding management quality initiative, in an Australian cardiac surgery unit

Background: Bleeding management in cardiac surgery is challenging. Many guidelines exist to support bleeding management; however, literature demonstrates wide variation in practice. In 2012, a quality initiative was undertaken at The Prince Charles Hospital, Australia to improve bleeding management for cardiac surgery patients. The implementation of the quality initiative resulted in significant reductions in the incidence of blood transfusion, re-exploration for bleeding; superficial leg and chest wound infections; length of hospital stay, and cost. Given the success of the initiative, we sought to answer the question; “How and why was the process of implementing a bleeding management quality initiative in the cardiac surgery unit successful, and sustainable?” Methods: A retrospective explanatory case study design was chosen to explore the quality initiative. Analysis of the evidence was reviewed through phases of the ‘Knowledgeto Action’ planned change model. Data was derived from: (1) document analysis, (2) direct observation of the local environment, (3) clinical narratives from interviews, and analysed with a triangulation approach. The study period extended from 10/2011 to 6/2013. Results: Results demonstrated the complexity of changing practice, as well as the significant amount of dedicated time and effort required to support individual, department and system wide change. Results suggest that while many clinicians were aware of the potential to apply improved practice, numerous barriers and challenges needed to be overcome to implement change across multiple disciplines and departments. Conclusions: The key successful components of the QI were revealed through the case study analysis as: (1) an appropriately skilled project manager to facilitate the implementation process; (2) tools to support changes in workflow and decision making including a bleeding management treatment algorithm with POCCTs; (3) strong clinical leadership from the multidisciplinary team and; (4) the evolution of the project manager position into a perpetual clinical position to support sustainability.</p

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

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.OvRCCs (n\ua0=\ua05) collected and processed in standard human blood collection packs, and equivalent huRCCs provided by Australian Red Cross Lifeblood (n\ua0=\ua05), were stored at 2-6°C for 42\ua0days, with samples collected weekly. Haemolysis index was determined by measuring supernatant haemoglobin concentration. Biochemical parameters were evaluated using a blood gas analyser. Energy metabolites and biologically active lipids were measured using commercial assays. Osmotic fragility was determined by lysis in various saline concentrations. Extracellular vesicles were characterized by nanoparticle tracking analysis.Ovine red blood cells (RBCs) are double in number, smaller in size and more fragile than human RBCs. Haematological values were unchanged throughout storage. In contrast, biochemical and metabolic values, and haemolysis index in three of the five ovRCCs exceeded huRCCs licensing criteria by day 42. Accumulation of extracellular vesicles and biologically active lipids was comparable between huRCCs and ovRCCs.This study documents similarities and differences in the storage lesion of ovRCCs and huRCCs. This new information will guide the design of ovine transfusion models to enhance translation of findings to human transfusion settings