A bispecific antibody targeting HLA-DQ2.5-gluten peptides potently blocks gluten-specific T cells induced by gluten ingestion in patients with celiac disease.

The gluten-free diet for celiac disease (CeD) is restrictive and often fails to induce complete symptom and/or mucosal disease remission. Central to CeD pathogenesis is the gluten-specific CD4+ T cell that is restricted by HLA-DQ2.5 in over 85% of CeD patients, making HLA-DQ2.5 an attractive target for suppressing gluten-dependent immunity. Recently, a novel anti-HLA-DQ2.5 antibody that specifically recognizes the complexes of HLA-DQ2.5 and multiple gluten epitopes was developed (DONQ52). OBJECTIVE: To assess the ability of DONQ52 to inhibit CeD patient-derived T-cell responses to the most immunogenic gluten peptides that encompass immunodominant T cell epitopes. METHODS: We employed an in vivo gluten challenge model in patients with CeD that affords a quantitative readout of disease-relevant gluten-specific T-cell responses. HLA-DQ2.5+ CeD patients consumed food containing wheat, barley, or rye for 3 days with collection of blood before (D1) and 6 days after (D6) commencing the challenge. Peripheral blood mononuclear cells were isolated and assessed in an interferon (IFN)-γ enzyme-linked immunosorbent spot assay (ELISpot) testing responses to gluten peptides encompassing a series of immunodominant T cell epitopes. The inhibitory effect of DONQ52 (4 or 40 µg/mL) was assessed and compared to pan-HLA-DQ blockade (SPVL3 antibody). RESULTS: In HLA-DQ2.5+ CeD patients, DONQ52 reduced T cell responses to all wheat gluten peptides to an equivalent or more effective degree than pan-HLA-DQ antibody blockade. It reduced T cell responses to a cocktail of the most immunodominant wheat epitopes by a median of 87% (IQR 72-92). Notably, DONQ52 also substantially reduced T-cell responses to dominant barley hordein and rye secalin derived peptides. DONQ52 had no effect on T-cell responses to non-gluten antigens. CONCLUSION: DONQ52 can significantly block HLA-DQ2.5-restricted T cell responses to the most highly immunogenic gluten peptides in CeD. Our findings support in vitro data that DONQ52 displays selectivity and broad cross-reactivity against multiple gluten peptide:HLA-DQ2.5 complexes. This work provides proof-of-concept multi-specific antibody blockade has the potential to meaningfully inhibit pathogenic gluten-specific T-cell responses in CeD and supports ongoing therapeutic development.

The Effect of Nb, Ta, and Ti on the Oxidation of a New Polycrystalline Ni-Based Superalloy.

The effect of variations in Nb, Ta, and Ti concentrations in exchange for Al on the oxidation resistance of a new polycrystalline Ni-based superalloy (C19) was studied in air at 800 °C for up to 1000 h. An external scale of Ti-doped Cr2O3 and a sub-scale of discontinuous Al2O3 intrusions formed on the surface of all the studied alloys. Contrary to other reports, increasing the Nb concentration improved the oxidation performance and may have promoted the formation of a CrTaO4 layer, thereby reducing oxygen ingress. The addition of Ta also significantly improved oxidation resistance and reduced the depth of the Al2O3 intrusions. Increasing the Ti concentration did not significantly affect the oxidation performance, potentially due to the relatively low Ti concentrations investigated. Several of the studied alloys with modified Ta and Ti concentrations showed regions of continuous Al2O3 scale formation, suggesting that the compositions are in a transition regime between Cr2O3-forming and Al2O3-forming behaviour. The findings suggested that part of the Ti content in C19 could potentially be replaced with Nb, Ta and/or other elements to further enhance oxidation resistance and other desirable properties. Overall, the insights gained could serve as a guide to optimise the composition of C19 and similar alloys for enhanced oxidation resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s11085-023-10218-7.

What do the revised UK standards of proficiency mean for diagnostic radiography training? A regional radiographer focus group study.

INTRODUCTION: Revisions to the UK Health and Care Professions Council (HCPC) standards of proficiency for diagnostic radiographers came into effect on September 1st 2023. Changes include an increase of proficiencies in CT and extended to MRI imaging. As workforce support the development of learners to meet stage outcomes in practice, this study aimed to understand the radiographers' expectations of future learners' training to meet the new standards of proficiency. METHODS: Snowball sampling was used to invite practice educators/student supervisors and department leads within the 21 NHS Trusts in the North East and Yorkshire region providing diagnostic radiography practice placements. Online focus groups used a semi structured topic guide to explore the expectations of student performance during different stages of their training, and on different types of pre-registration programmes. Participants views were sought on considerations for appropriate assessment. Thematic analysis was supported by NVivo software. RESULTS: Fifteen diagnostic radiographers across 11 NHS trusts participated in 5 focus groups in November 2022. The findings showed consistency in expectations of student performance in projectional radiography, patient care and communication. Participants felt some standards of proficiency were beyond threshold competency, or current practices were a barrier in supporting learning. Participants felt assessment over a period and range of examinations in the clinical environment gave a fairer picture of student performance. CONCLUSION: There is uncertainty and perceived barriers in supporting future diagnostic radiography training in the practice setting. IMPLICATIONS FOR PRACTICE: Further work will be needed to identify and support appropriate learning opportunities and stage outcomes if learners are to meet the breadth of HCPC standards of proficiency with some consistency.

Evaluating the role of the diagnostic radiographer in identifying child safeguarding concerns: A knowledge, attitude and practice survey approach.

INTRODUCTION: Child safeguarding and the appropriate identification of suspected victims represents a global phenomenon. Diagnostic imaging is acknowledged as a contributory diagnostic service but the role of the radiographer in the identification and escalation process is less well understood. METHOD: A Knowledge, Attitude and Practice (KAP) survey was constructed to evaluate knowledge base in the context of the patient-radiographer interaction, the shaping of attitude towards child safeguarding and attitudes held towards their role plus the actual practical experiences of managing child safeguarding concerns. RESULTS: Respondents demonstrated a inconsistent knowledge base with respect to physical, social and radiographic signs and symptoms of child safeguarding concern. A positive attitude towards the role of the radiographer in child safeguarding was demonstrated but one that was shaped more by experience than pre-registration education. Assessment of concerns was chiefly influenced by clinical history and appreciation of aetiology. Practically, radiographers have infrequent involvement with the identification and escalation of concerns. Whilst some statistically significant relationships between responses and demographics did exist, these were either sporadic or argued to be a result of natural variation. CONCLUSION: Assessment of physical and social signs of child safeguarding concern are argued to be becoming more challenging. Radiological signs continue to be visible to radiographers but with increasing use of other imaging modalities these signs are becoming more varied in nature and are providing new challenges. Radiographers are capable of escalation when required to do so. IMPLICATIONS FOR PRACTICE: To maximise the contribution of the profession, education needs to account for imaging modality worked with, in combination with an understanding of related aetiology. Previously existing concerns with respect to escalating processes are no longer in evidence and radiographers are both willing and able to contribute to that process.

Evaluating Wagner Oxidation Criteria for Protective Al2O3 Scale Formation in Ni-Based Superalloys.

An assessment is made of the Wagner transition criteria for predicting the formation of a continuous Al2O3 scale in Ni-based superalloys. Predictions are compared with data from an experimental Ni-based superalloy as well as commercial superalloys for which published data are available. The methodology was generally successful in predicting the transition temperature of the commercial superalloys but underpredicted the transition temperature of the experimental superalloy by approximately 50-100 °C. The difference in the transition temperature of the experimental superalloy to form a continuous Al2O3 scale is primarily attributed to a complex oxide subscale that increased the internal volume fraction of oxide and led to reduced oxygen ingress. The sensitivity and limitations of the methodology are discussed, and recommendations are made to refine the methodology to facilitate the interpretation of oxidation behaviour in polycrystalline Ni-based superalloys. Supplementary Information: The online version contains supplementary material available at 10.1007/s11085-023-10163-5.

D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

Artificial intelligence in radiography: Where are we now and what does the future hold?

OBJECTIVES: This paper will outline the status and basic principles of artificial intelligence (AI) in radiography along with some thoughts and suggestions on what the future might hold. While the authors are not always able to separate the current status from future developments in this field, given the speed of innovation in AI, every effort has been made to give a view to the present with projections to the future. KEY FINDINGS: AI is increasingly being integrated within radiography and radiographers will increasingly be working with AI based tools in the future. As new AI tools are developed it is essential that robust validation is undertaken in unseen data, supported by more prospective interdisciplinary research. A framework of stronger, more comprehensive approvals are recommended and the involvement of service users, including practitioners, patients and their carers in the design and implementation of AI tools is essential. Clearer accountability and medicolegal frameworks are required in cases of erroneous results from the use of AI-powered software and hardware. Clearer career pathways and role extension provision for healthcare practitioners, including radiographers, are required along with education in this field where AI will be central. CONCLUSION: With the current growth rate of AI tools it is expected that many of the applications in medical imaging will continue to develop to more accurate, less expensive and more readily available versions moving from the bench to the bedside. The hope is that, alongside efficiency and increased patient throughput, patient centred care and precision medicine will find their way in, so we will not only deliver a faster, safer, seamless clinical service but also one that will have the patients at its heart. IMPACT FOR PRACTICE: AI is already reaching clinical practice in many forms and its presence will continue to increase over the short and long-term future. Radiographers must learn to work with AI, embracing it and maximising the positive outcomes from this new technology.

There's nothing plain about projection radiography! A discussion paper.

OBJECTIVES: Unlike the technological advances in cross-sectional imaging, the adoption of CR and DR has been relatively overlooked in terms of the additional radiographer skills and competences required for optimal practice. Furthermore, projection radiography is often referred to as basic, plain or other words suggesting simplicity or entry-level skill requirements. Radiographers' professional identity is connected with the discourse expressed via the language used in daily practice and consequently, if the perception of projection radiography is regarded as simple practice not requiring much reflection or complex decision-making, apathy and carelessness may arise. The purpose of this narrative review was to raise projection radiography from its longstanding lowly place and re-position it as a specialist imaging field. KEY FINDINGS: Danish pre-registration radiography curricula contain little mention of projection radiography and a low proportion (n = 17/144; 11.8%) of Danish radiography students chose to focus on projection radiography within publicly available BSc. theses between 2016 and 2020 as compared to topics related to CT and MRI (n = 60/144; 41.7%). CONCLUSION: By changing how we as the profession perceive the role and position of projection radiography, we can start to rebuild its lost prestige and demand a greater, more detailed and clinically relevant educational offering from academic partners. For this to commence, the language and terminology we use to describe ourselves and tasks undertaken must reflect the complexity of the profession. IMPLICATIONS FOR PRACTICE: Regardless of imaging modality, every patient should be assured that a radiographer with expertise in acquiring images of diagnostic quality undertakes their examination. Reclaiming the prestige of projection radiography may lead students and radiographers to recognize projection radiography as a demanding specialist field for the benefit of the patients.

Local diagnostic reference levels for skeletal surveys in suspected physical child abuse.

INTRODUCTION: The purpose was to determine if an age based, local diagnostic reference level for paediatric skeletal surveys could be established using retrospective data. METHODS: All children below two years of age referred for a primary skeletal survey as a result of suspected physical abuse during 2017 or 2018 (n = 45) were retrospectively included from a large Danish university hospital. The skeletal survey protocol included a total of 33 images. Dose Area Product (DAP) and acquisition parameters for all images were recorded from the Picture Archival and Communication System (PACS) and effective dose was estimated. The 75th percentile for DAP was considered as the diagnostic reference level (DRL). RESULTS: The 75th percentile for DAP was 314 mGy∗cm2, 520 mGy∗cm2 and 779 mGy∗cm2 for children <1 month, 1-11 months and 12 < 24 months of age respectively. However, only the age group 1-11 months had a sufficient number of children (n = 27) to establish a local DRL. Thus, for the other groups the DAP result must be interpreted with caution. Effective dose was 0.19, 0.26 and 0.18 mSv for children <1, 1-11 months and 12 < 24 months of age respectively. CONCLUSION: For children between 1 and 11 months of age, a local diagnostic reference level of 520 mGy∗cm2 was determined. This may be used as an initial benchmark for primary skeletal surveys as a result of suspected physical abuse for comparison and future discussion. IMPLICATIONS FOR PRACTICE: While the data presented reflects the results of a single department, the suggested diagnostic reference level may be used as a benchmark for other departments when auditing skeletal survey radiation dose.

Whole blood interleukin-2 release test to detect and characterize rare circulating gluten-specific T cell responses in coeliac disease.

Whole blood cytokine release assays (CRA) assessing cellular immunity to gluten could simplify the diagnosis and monitoring of coeliac disease (CD). We aimed to determine the effectiveness of electrochemiluminescence CRA to detect responses to immunodominant gliadin peptides. HLA-DQ2·5+ CD adults (cohort 1, n = 6; cohort 2, n = 12) and unaffected controls (cohort 3, n = 9) were enrolled. Cohort 1 had 3-day gluten challenge (GC). Blood was collected at baseline, and for cohort 1 also at 3 h, 6 h and 6 days after commencing 3-day GC. Gliadin peptide-stimulated proliferation, interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and 14- and 3-plex electrochemiluminescence CRA were performed. Poisson distribution analysis was used to estimate responding cell frequencies. In cohort 1, interleukin (IL)-2 dominated the gliadin peptide-stimulated cytokine release profile in whole blood. GC caused systemic IL-2 release acutely and increased gliadin peptide-stimulated IFN-γ ELISPOT and whole blood CRA responses. Whole blood CRA after GC was dominated by IL-2, but also included IFN-γ, C-X-C motif chemokine ligand 10/IFN-γ-induced protein 10 (CXCL10/IP-10), CXCL9/monokine induced by IFN-γ (MIG), IL-10, chemokine (C-C motif) ligand 3/macrophage inflammatory protein 1-alpha (CCL3/MIP-1α), TNF-α and IL-8/CXCL8. In cohorts 2 and 3, gliadin peptide-stimulated whole blood IL-2 release was 100% specific and 92% sensitive for CD patients on a gluten-free diet; the estimated frequency of cells in CD blood secreting IL-2 to α-gliadin peptide was 0·5 to 11 per ml. Whole blood IL-2 release successfully mapped human leucocyte antigen (HLA)-DQ2·5-restricted epitopes in an α-gliadin peptide library using CD blood before and after GC. Whole blood IL-2 release assay using electrochemiluminescence is a sensitive test for rare gliadin-specific T cells in CD, and could aid in monitoring and diagnosis. Larger studies and validation with tetramer-based assays are warranted.

Patient centred care in diagnostic radiography (Part 3): Perceptions of student radiographers and radiography academics.

INTRODUCTION: Awareness is growing of the importance of patient centered care (PCC) in diagnostic radiography. PCC is embedded within professional body publications and guidance documents, but there is limited research evidence exploring the perceptions of student radiographers and radiography academics. METHODS: This paper reports Stage 1 and Stage 2 of the project from the perspective of radiography academic and student radiographer participants, and compares these to the perspectives of service users, clinical radiographers and radiography managers reported previously. Stage 1 used an online survey tool to gauge participant agreement with a series of attitudinal statements. Stage 2 used situational vignettes to promote discussion and debate about PCC approaches. RESULTS: Response rates to the Stage 1 survey were above the minimum threshold, with 50 responses from student radiographers and 38 responses from radiography academics. Stage 1 participants were asked to participate in Stage 2 on a voluntary basis. As with service users and service deliverers, care communication, event interactions and control over environment were the key influences on PCC. However, students highlighted differences between reported and observed levels of PCC. CONCLUSION: There is some way to go to embed PCC in diagnostic radiography practice. As impartial observers of radiography practice, student radiographers highlight the difference between service users and service deliverer's perceptions of PCC. Whilst the focus of clinical radiographers remains on efficiency, it is difficult for student radiographers to challenge the accepted norm. Role models are required to promote PCC behaviours and a holistic approach in radiography practice. IMPLICATIONS FOR PRACTICE: A package of educational support and audit tools will be made available to support both service deliverers and student radiographers to deliver PCC.

Patient centred care in diagnostic radiography (Part 1): Perceptions of service users and service deliverers.

INTRODUCTION: There is growing awareness of the importance of patient centered care (PCC) in health care. Within Radiography in the UK, elements of PCC are embedded within professional body publications and guidance documents. However, there is limited research evidence exploring whether perceptions of PCC are equivalent between those delivering (radiographers) and those experiencing (patient) care. This study aimed to address this gap by determining compatibility in perceptions of PCC between those using and those delivering radiography services. This is the first step in developing measurable indicators of PCC in diagnostic radiography. METHODS: A multi-method two stage approach was undertaken using survey and interview data collection techniques. Ethical approval was granted by University of Derby College of Health & Social Care Ethics committee. This paper reports Stage 1 of the study, the online, cross sectional survey. Participants were asked to indicate their level of agreement to a series of attitudinal statements using a 5-point Likert scale. Statements were paired, but not co-located to increase validity. Participants were invited to provide free text comments to supplement their responses. Stage 2 of the project is reported separately. RESULTS: Survey responses were received from all 3 participant subgroups. A minimum response rate of 30 participants per sub-group was set as a target. Response rates varied across subgroups, with only radiography managers failing to meet the expected response threshold. Wide disparity between perceptions of service users and those delivering radiography services on what constitutes high quality PCC was evident. CONCLUSION: It is evident that there is still work required to ensure parity between expectations of service users and deliverers on what constitutes high quality PCC. IMPLICATIONS FOR PRACTICE: Further work is required to identify measurable service delivery outcomes that represent PCC within radiographic practice.

Computer based simulation in CT and MRI radiography education: Current role and future opportunities.

OBJECTIVE: The use of Computer-based simulation (CBS), a form of simulation which utilises digital and web based platforms, is widely acknowledged in healthcare education. This literature review explores the current evidence relating to CBS activities in supporting radiographer education in CT and MRI. KEY FINDINGS: Journal articles published between 2010 and 2020 were reviewed (n = 663). The content was evaluated and summarised with the following headings; current utility, overview of CBS types, knowledge acquisition and evaluation, and student perspective. CBS utility in CT and MRI radiography education is limited. Its current use is for pre-registration education, and the interfaces used vary in design but are predominantly used as a preclinical learning tool to support the training of geometric scan planning, image acquisition and reconstruction, and associated technical skills. CBS was positively acknowledged by student radiographers; based on its inherent flexibility, self-paced learning and the ability to practice in a safe environment. Nonetheless, the educational validation of CBS in CT and MRI education pertaining to knowledge and skill acquisition has not been fully assessed through rigorous academic assessments and metrics. CONCLUSION: The current use of CBS in CT and MRI education is limited. The development of software programmes with functionality and capability that correlates with current clinical practice is imperative; and to enable more research in CBS utility to be undertaken to establish the efficacy of this pedagogical approach. IMPLICATIONS FOR PRACTICE: Due to limited placement opportunities, the use of simulation is increasing and evolving; in line with the approach to design and deliver high quality Simulation Based Education (SBE) in Diagnostic Radiography education. The continued development, utility and evaluation of CBS interfaces to support student radiographers at pre and post registration level is therefore essential.

Patient centred care in diagnostic radiography (Part 2): A qualitative study of the perceptions of service users and service deliverers.

INTRODUCTION: There is growing awareness of the importance of patient centred care (PCC) in health care. Within Radiography in the UK, elements of PCC are embedded within professional body publications and guidance documents, but there is limited research evidence exploring whether perceptions of PCC are equivalent between those delivering (radiographers) and those experiencing (patient) care. This study aimed to address this gap by determining compatibility in perceptions of PCC between those using and those delivering radiography services in order to develop measurable indicators of PCC. METHODS: This project was funded by the College of Radiographers Industry Partnership Scheme. Ethical approval was granted by the University of Derby College of Health & Social Care Ethics committee. This paper reports Stage 2 of the project, which was a series of focus groups and telephone interviews to enable deeper discussion and exploration of PCC. Situational vignettes were used to promote discussion and debate and encourage suggestions for PCC approaches. Audit tools to assess engagement with PCC were developed at individual and organisational level. RESULTS: Four focus groups and six telephone interviews were carried out in total. Focus groups were held in a variety of locations to promote attendance. Telephone interviews were used to capture participants who could not attend a focus group in person. Disparity between perceptions of service users and those delivering radiography services on what constitutes high quality PCC was evident. Perceived levels of care and the effectiveness of communication appeared to be the key influences on whether PCC was delivered. CONCLUSION: It is evident from the results of Stage 1 and Stage 2 that we have some way to go before we have parity in how care within diagnostic radiography is perceived, experienced and delivered. Audit tools and an educational toolkit are offered as ways to support increased PCC within diagnostic radiography practice. IMPLICATIONS FOR PRACTICE: Several service improvements and audit tools are offered to support the increased delivery of PCC.

Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory.

Coronavirus disease 2019 (COVID-19) is associated with extreme inflammatory response, disordered hemostasis and high thrombotic risk. A high incidence of thromboembolic events has been reported despite thromboprophylaxis, raising the question of a more effective anticoagulation. First-line hemostasis tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and D-dimers are proposed for assessing thrombotic risk and monitoring hemostasis, but are vulnerable to many drawbacks affecting their reliability and clinical relevance. Specialized hemostasis-related tests (soluble fibrin complexes, tests assessing fibrinolytic capacity, viscoelastic tests, thrombin generation) may have an interest to assess the thrombotic risk associated with COVID-19. Another challenge for the hemostasis laboratory is the monitoring of heparin treatment, especially unfractionated heparin in the setting of an extreme inflammatory response. This review aimed at evaluating the role of hemostasis tests in the management of COVID-19 and discussing their main limitations.

Using avatars in weight management settings: A systematic review.

BACKGROUND: Obesity interventions rely predominantly on managing dietary intake and/or increasing physical activity but sustained adherence to behavioural regimens is often poor. Avatar technology is well established within the computer gaming industry and evidence suggests that virtual representations of self may impact real-world behaviour, acting as a catalyst for sustained weight loss behaviour modification. However, the effectiveness of avatar technology in promoting weight loss is unclear. AIMS: We aimed to assess the quantity and quality of empirical support for the use of avatar technologies in adult weight loss interventions. METHOD: A systematic review of empirical studies was undertaken. The key objectives were to determine if: (i) the inclusion of avatar technology leads to greater weight loss achievement compared to routine intervention; and (ii) whether weight loss achievement is improved by avatar personalisation (avatar visually reflects self). RESULTS: We identified 6 papers that reported weight loss data. Avatar-based interventions for weight loss management were found to be effective in the short (4-6 weeks) and medium (3-6 months) term and improved weight loss maintenance in the long term (12 months). Only 2 papers included avatar personalisation, but results suggested there may be some added motivational benefit. CONCLUSIONS: The current evidence supports that avatars may positively impact weight loss achievement and improve motivation. However, with only 6 papers identified the evidence base is limited and therefore findings need to be interpreted with caution.

Andexanet alfa for the reversal of factor Xa inhibitors.

INTRODUCTION: Andexanet alfa is a recombinant modified factor Xa protein that has been developed to reverse factor Xa inhibitors. Since May 2018, the FDA has approved its utilization in patients treated with apixaban and rivaroxaban in case of life-threatening or uncontrolled bleeding. On 28 of February 2019, the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a conditional marketing authorization for andexanet alfa in Europe. Area covered: The authors provide an overview of andexanet alfa development and its pharmacokinetic and pharmacodynamic properties. The results of the clinical phase III trial ANNEXA as well as current limitations related to andexanet alfa are also discussed. Expert opinion: Although phase I and II studies have proven that andexanet alfa can be effective in reversing the effect of factor Xa inhibitors, its efficacy in major bleeding patients has only been shown for apixaban and rivaroxaban, without any comparator group. Well-designed studies comparing the efficacy and safety of andexanet alfa to other reversal strategies are required to confirm preliminary data. The benefit of andexanet alfa in specific settings needs to be investigated and its use in clinical practice needs to be facilitated by the implementation of international guidelines.