Insights from developing and evaluating the NHS blood choices transfusion app to support junior and middle-grade doctor decision making against guidelines.

OBJECTIVES: To: 1. Develop a CE-marked smartphone App to support doctors' concordance with transfusion guidelines in non-bleeding adult patients, emphasising informed consent and anaemia management. 2. Test App accuracy and potential to improve user decisions. BACKGROUND: Studies have shown inappropriate use of blood components and that most junior doctors own smartphones with medical apps. METHODS: A multidisciplinary team developed App screens and logic through an iterative process based on national guidelines. Thirty medical or surgical transfusion scenarios were developed based on national guidelines and each sent to Consultant Haematologist experts in Transfusion Medicine. To obtain a clinical consensus and exclude ambiguous scenarios, their independent decisions and associated certainty were compared. The consensus clinical decision was then compared with guidance from the App. To explore potential App impact on simulated user decisions, 26 junior doctors responded to five transfusion scenarios before and after access to the App. RESULTS: The Blood Choices App agreed with 91% (95% CI: 72%-99%) of expert decisions with a sensitivity of 100% (69% to 100%) and specificity of 85% (55%-98%). Excluding one malfunction scenario, the App had the potential to increase correct decisions by junior doctors from 83% (73%-90%) pre-App use to 96% (88%-99%) post (p-value 0.013), with 90% (67%-99%) saying they would use it in practice. CONCLUSIONS: Transfusion guidelines can be converted into an App with potential to improve guideline concordance. However, evaluating such Apps is essential to understand their limitations, detect malfunctions and prevent harm.

The EHA Research Roadmap: Transfusion Medicine.

In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research 1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1-2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including eleven sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European hematology research. The 11 EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cell-based Immune Therapies; and Gene Therapy.

Transfusion 2024: A 5-year plan for clinical and laboratory transfusion in England.

The Transfusion 2024 plan outlines key priorities for clinical and laboratory transfusion practice for safe patient care across the NHS for the next 5 years. It is based on the outcomes of a multi-professional symposium held in March 2019, organised by the National Blood Transfusion Committee (NBTC) and NHS Blood and Transplant (NHSBT), attended and supported by Professor Keith Willet and Dame Sue Hill on behalf of NHS England and Improvement. This best practice guidance contained within this publication will facilitate the necessary change in pathway design to meet the transfusion challenges and pressures for the restoration of a cohesive, and functional, healthcare system across the NHS following the COVID-19 pandemic.

A Decade of Damage Control Resuscitation: New Transfusion Practice, New Survivors, New Directions.

OBJECTIVE: The aim of this study was to identify the effects of recent innovations in trauma major hemorrhage management on outcome and transfusion practice, and to determine the contemporary timings and patterns of death. BACKGROUND: The last 10 years have seen a research-led change in hemorrhage management to damage control resuscitation (DCR), focused on the prevention and treatment of trauma-induced coagulopathy. METHODS: A 10-year retrospective analysis of prospectively collected data of trauma patients who activated the Major Trauma Centre's major hemorrhage protocol (MHP) and received at least 1 unit of red blood cell transfusions (RBC). RESULTS: A total of 1169 trauma patients activated the MHP and received at least 1 unit of RBC, with similar injury and admission physiology characteristics over the decade. Overall mortality declined from 45% in 2008 to 27% in 2017, whereas median RBC transfusion rates dropped from 12 to 4 units (massive transfusion rates from 68% to 24%). The proportion of deaths within 24 hours halved (33%-16%), principally with a fall in mortality between 3 and 24 hours (30%-6%). Survivors are now more likely to be discharged to their own home (57%-73%). Exsanguination is still the principal cause of early deaths, and the mortality associated with massive transfusion remains high (48%). Late deaths are now split between those due to traumatic brain injury (52%) and multiple organ dysfunction (45%). CONCLUSIONS: There have been remarkable reductions in mortality after major trauma hemorrhage in recent years. Mortality rates continue to be high and there remain important opportunities for further improvements in these patients.

Cost-effectiveness of cell salvage and donor blood transfusion during caesarean section: results from a randomised controlled trial.

OBJECTIVES: To evaluate the cost-effectiveness of routine use of cell salvage during caesarean section in mothers at risk of haemorrhage compared with current standard of care. DESIGN: Model-based cost-effectiveness evaluation alongside a multicentre randomised controlled trial. Three main analyses were carried out on the trial data: (1) based on the intention-to-treat principle; (2) based on the per-protocol principle; (3) only participants who underwent an emergency caesarean section. SETTING: 26 obstetric units in the UK. PARTICIPANTS: 3028 women at risk of haemorrhage recruited between June 2013 and April 2016. INTERVENTIONS: Cell salvage (intervention) versus routine care without salvage (control). PRIMARY OUTCOME MEASURES: Cost-effectiveness based on incremental cost per donor blood transfusion avoided. RESULTS: In the intention-to-treat analysis, the mean difference in total costs between cell salvage and standard care was £83. The estimated incremental cost-effectiveness ratio (ICER) was £8110 per donor blood transfusion avoided. For the per-protocol analysis, the mean difference in total costs was £92 and the ICER was £8252. In the emergency caesarean section analysis, the mean difference in total costs was £55 and the ICER was £13 713 per donor blood transfusion avoided. This ICER is driven by the increased probability that these patients would require a higher level of postoperative care and additional surgeries. The results of these analyses were shown to be robust for the majority of deterministic sensitivity analyses. CONCLUSIONS: The results of the economic evaluation suggest that while routine cell salvage is a marginally more effective strategy than standard care in avoiding a donor blood transfusion, there is uncertainty in relation to whether it is a less or more costly strategy. The lack of long-term data on the health and quality of life of patients in both arms of the trial means that further research is needed to fully understand the cost implications of both strategies. TRIAL REGISTRATION NUMBER: ISRCTN66118656.

A randomised controlled trial and economic evaluation of intraoperative cell salvage during caesarean section in women at risk of haemorrhage: the SALVO (cell SALVage in Obstetrics) trial.

BACKGROUND: Caesarean section is associated with blood loss and maternal morbidity. Excessive blood loss requires transfusion of donor (allogeneic) blood, which is a finite resource. Cell salvage returns blood lost during surgery to the mother. It may avoid the need for donor blood transfusion, but reliable evidence of its effects is lacking. OBJECTIVES: To determine if routine use of cell salvage during caesarean section in mothers at risk of haemorrhage reduces the rates of blood transfusion and postpartum maternal morbidity, and is cost-effective, in comparison with standard practice without routine salvage use. DESIGN: Individually randomised controlled, multicentre trial with cost-effectiveness analysis. Treatment was not blinded. SETTING: A total of 26 UK obstetric units. PARTICIPANTS: Out of 3054 women recruited between June 2013 and April 2016, we randomly assigned 3028 women at risk of haemorrhage to cell salvage or routine care. Randomisation was stratified using random permuted blocks of variable sizes. Of these, 1672 had emergency and 1356 had elective caesareans. We excluded women for whom cell salvage or donor blood transfusion was contraindicated. INTERVENTIONS: Cell salvage (intervention) versus routine care without salvage (control). In the intervention group, salvage was set up in 95.6% of the women and, of these, 50.8% had salvaged blood returned. In the control group, 3.9% had salvage deployed. MAIN OUTCOME MEASURES: Primary - donor blood transfusion. Secondary - units of donor blood transfused, time to mobilisation, length of hospitalisation, mean fall in haemoglobin, fetomaternal haemorrhage (FMH) measured by Kleihauer-Betke test, and maternal fatigue. Analyses were adjusted for stratification factors and other factors that were believed to be prognostic a priori. Cost-effectiveness outcomes - costs of resources and service provision taking the UK NHS perspective. RESULTS: We analysed 1498 and 1492 participants in the intervention and control groups, respectively. Overall, the transfusion rate was 2.5% in the intervention group and 3.5% in the control group [adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42 to 1.01; p = 0.056]. In a planned subgroup analysis, the transfusion rate was 3.0% in the intervention group and 4.6% in the control group among emergency caesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 1.8% in the intervention group and 2.2% in the control group among elective caesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46, suggesting that the difference in effect between subgroups was not statistically significant). Secondary outcomes did not differ between groups, except for FMH, which was higher under salvage in rhesus D (RhD)-negative women with RhD-positive babies (25.6% vs. 10.5%, adjusted OR 5.63, 95% CI 1.43 to 22.14; p = 0.013). No case of amniotic fluid embolism was observed. The additional cost of routine cell salvage during caesarean was estimated, on average, at £8110 per donor blood transfusion avoided. CONCLUSIONS: The modest evidence for an effect of routine use of cell salvage during caesarean section on rates of donor blood transfusion was associated with increased FMH, which emphasises the need for adherence to guidance on anti-D prophylaxis. We are unable to comment on long-term antibody sensitisation effects. Based on the findings of this trial, cell salvage is unlikely to be considered cost-effective. FUTURE WORK: Research into risk of alloimmunisation among women exposed to cell salvage is needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN66118656. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 2. See the NIHR Journals Library website for further project information.

Cell salvage and donor blood transfusion during cesarean section: A pragmatic, multicentre randomised controlled trial (SALVO).

BACKGROUND: Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement. METHODS AND FINDINGS: We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference -1.03, 95% CI -2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects. CONCLUSIONS: The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant. TRIAL REGISTRATION: This trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656.

Does current evidence support the use of intraoperative cell salvage in reducing the need for blood transfusion in caesarean section?

PURPOSE OF REVIEW: An important cause of maternal morbidity and direct maternal death is obstetric haemorrhage at caesarean section. Concerns regarding allogeneic blood safety, limited blood supplies and rising health costs have collectively generated enthusiasm for the utility of methods intended to reduce the use of allogeneic blood transfusion in cases of haemorrhage at caesarean section. This can be achieved by intraoperative cell salvage (IOCS). The aim of this review is to summarize and examine the evidence for the efficacy of IOCS during caesarean section, in women at risk of haemorrhage, in reducing the need for allogeneic blood transfusion. RECENT FINDINGS: The majority of the evidence currently available is from case reports and case series. Although this evidence appears to support the use of IOCS in obstetrics, strong clinical evidence or economic effectiveness from clinical trials are essential to support the routine practice of IOCS in obstetrics. SUMMARY: Current evidence is limited to reported case series and two small controlled studies. Overall, IOCS may reduce the need for allogeneic blood transfusions during caesarean section. Future large randomized trials are required to assess effectiveness, cost effectiveness and safety. The results of the current ongoing SALVO (A randomised controlled trial of intra-operative cell salvage during caesarean section in women at risk of haemorrhage) trial will shed light on these aspects.

How we manage the haematological aspects of major obstetric haemorrhage.

Major obstetric haemorrhage (MOH) remains an important medical challenge worldwide, contributing to significant maternal morbidity and mortality. Prompt and appropriate management is essential if we are to improve outcomes and reduce substandard care that may result in adverse consequences. This review describes the current understanding of the pathophysiological aspects of MOH together with the principles of transfusion and haemostatic therapy, with emphasis on a coordinated multidisciplinary approach. We also highlight the current lack of evidence available from randomized controlled trials to inform best practice and the need to prioritize research in this key clinical area.

A major haemorrhage protocol improves the delivery of blood component therapy and reduces waste in trauma massive transfusion.

BACKGROUND: Major haemorrhage protocols (MHP) are required as part of damage control resuscitation regimens in modern trauma care. The primary objectives of this study were to ascertain whether a MHP improved blood product administration and reduced waste compared to traditional massive transfusion protocols (MTP). METHODS: Datasets on adult trauma admissions 1 year prior and 1 year post implementation of a MHP at a Level 1 trauma centre were obtained from the trauma registry. Demographic and clinical data were collected prospectively including mechanism of injury, physiological observations, ICU admission and length of stay. The volume of blood components (packed red blood cells, platelets, cryoprecipitate and fresh frozen plasma) issued, transfused, returned to stock and wasted within the first 24h was gathered retrospectively. RESULTS: Over the 2-year study period 2986 patient records were available for analysis. 40 patients required a 10+ Units of packed red blood ells transfusion in the MTP group vs. 56 patients post MHP implementation. The administration of blood component therapy improved significantly post MHP implementation. FFP:PRBC transfusion improved from 1:3 to 1:2 (p<0.01) and CRYO:PRBC improved from 1:10 to 1:7 (p<0.05). We reported a significant reduction in the waste of platelets from 14% to 2% (p<0.01). Outcomes had improved: Median hospital length of stay was reduced from 54 days to 26 days (p<0.05). CONCLUSION: Implementation of a MHP results in improved delivery of blood components and a reduction in the waste of blood products compared to the older model of MTP. In combination with educational programmes MHP can significantly improve blood product administration and patient outcomes in trauma haemorrhage. LEVEL OF EVIDENCE: Level III diagnostic test study.

Guideline on the investigation and management of acute transfusion reactions. Prepared by the BCSH Blood Transfusion Task Force.

Although acute non-haemolytic febrile or allergic reactions (ATRs) are a common complication of transfusion and often result in little or no morbidity, prompt recognition and management are essential. The serious hazards of transfusion haemovigilance organisation (SHOT) receives 30-40 reports of anaphylactic reactions each year. Other serious complications of transfusion, such as acute haemolysis, bacterial contamination, transfusion-related acute lung injury (TRALI) or transfusion-associated circulatory overload (TACO) may present with similar clinical features to ATR. This guideline describes the approach to a patient developing adverse symptoms and signs related to transfusion, including initial recognition, establishing a likely cause, treatment, investigations, planning future transfusion and reporting within the hospital and to haemovigilance organisations. Key recommendations are that adrenaline should be used as first line treatment of anaphylaxis, and that transfusions should only be carried out where patients can be directly observed and where staff are trained in manging complications of transfusion, particularly anaphylaxis. Management of ATRs is not dependent on classification but should be guided by symptoms and signs. Patients who have experienced an anaphylactic reaction should be discussed with an allergist or immunologist, in keeping with UK resuscitation council guidelines.

Gaps in the evidence for prevention and treatment of maternal anaemia: a review of systematic reviews.

BACKGROUND: Anaemia, in particular due to iron deficiency, is common in pregnancy with associated negative outcomes for mother and infant. However, there is evidence of significant variation in management. The objectives of this review of systematic reviews were to analyse and summarise the evidence base, identify gaps in the evidence and develop a research agenda for this important component of maternity care. METHODS: Multiple databases were searched, including MEDLINE, EMBASE and The Cochrane Library. All systematic reviews relating to interventions to prevent and treat anaemia in the antenatal and postnatal period were eligible. Two reviewers independently assessed data inclusion, extraction and quality of methodology. RESULTS: 27 reviews were included, all reporting on the prevention and treatment of anaemia in the antenatal (n = 24) and postnatal periods (n = 3). Using AMSTAR as the assessment tool for methodological quality, only 12 of the 27 were rated as high quality reviews. The greatest number of reviews covered antenatal nutritional supplementation for the prevention of anaemia (n = 19). Iron supplementation was the most extensively researched, but with ongoing uncertainty about optimal dose and regimen. Few identified reviews addressed anaemia management post-partum or correlations between laboratory and clinical outcomes, and no reviews reported on clinical symptoms of anaemia. CONCLUSIONS: The review highlights evidence gaps including the management of anaemia in the postnatal period, screening for anaemia, and optimal interventions for treatment. Research priorities include developing standardised approaches to reporting of laboratory outcomes, and information on clinical outcomes relevant to the experiences of pregnant women.

UK guidelines on the management of iron deficiency in pregnancy.

Iron deficiency is the most common deficiency state in the world, affecting more than 2 billion people globally. Although it is particularly prevalent in less-developed countries, it remains a significant problem in the developed world, even where other forms of malnutrition have already been almost eliminated. Effective management is needed to prevent adverse maternal and pregnancy outcomes, including the need for red cell transfusion. The objective of this guideline is to provide healthcare professionals with clear and simple recommendations for the diagnosis, treatment and prevention of iron deficiency in pregnancy and the postpartum period. This is the first such guideline in the UK and may be applicable to other developed countries. Public health measures, such as helminth control and iron fortification of foods, which can be important to developing countries, are not considered here. The guidance may not be appropriate to all patients and individual patient circumstances may dictate an alternative approach.

Recent massive blood transfusion practice in England and Wales: view from a trauma registry.

BACKGROUND: Few studies have characterised massive blood transfusion (MBT) practice in UK trauma. This study describes the Trauma Audit and Research Network experience of MBT over a 4-year period, and examines variables predictive of MBT and mortality following MBT. METHODS: Prospectively collected data between 2005 and 2009 from the Trauma Audit and Research Network database were analysed. MBT incidence was examined, and patient characteristics, blood component usage and mortality compared to non-MBT patients. Clinical and injury features predictive of massive transfusion, and risk factors predictive of death in MBT, were analysed using multivariate logistic regression. RESULTS: 157 patients (0.4%) received MBT, with a mortality rate of 40.3%. MBT patients were younger, more likely to be male and to have sustained more severe trauma (median age 39.2 years, median Injury Severity Score 27, 78% male, p<0.01). No patients received platelets and fresh frozen plasma (FFP) in 1:1 ratios with packed red cells. Multivariate analysis showed: age, admission pulse rate, systolic blood pressure, and injury type; thoracic, abdominal, pelvis, were significant predictors of MBT. Injury Severity Score and admission pulse rate were also independent predictors of death in MBT, but level of platelet and FFP use were not found to be statistically significant. CONCLUSION: MBT is a rare event with high mortality in UK trauma. Haemostatic resuscitation is not currently practiced in the UK and the authors were unable to show that FFP and platelet use were significant predictors of survival in MBT.