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It has been possible to identify the sequence of chromosome 4 of the higher plant Arabidopsis thaliana. This chromosome is ecrocentric, with a shorter arm tipped by near-homogeneous ribosomal DNA repeats reaching for 3.5 Mb to the telomere. The complete sequence of 19,360,101 bp occurs in three contigs. Of these, two represent the short and long arms while the third, smaller one is found in the centromeric heterochromatin. The centromeric heterochromatin region of the chromosome was mapped cytogenetically to an approximately 4 Mb interval.

Objective: BreastCheck, the Irish Breast Screening Programme, has employed three different models of a full field digital mammography (FFDM) system since its transition to a digital service in 2007. The three models from GE Healthcare, Hologic and Sectra exhibit differences in their design and function, the most significant of which include anode target/filter choice, detector technology and the type of exposure automation. Methods: The aim of this study was to use the results from a clinical breast dose survey to examine the differences between three different FFDM models in terms of exposure selection, breast mean glandular dose (MGD) and automatic exposure control (AEC) dose contribution. Results: The accuracy of the dose estimation was improved by inclusion of the AEC pre-exposure dose contribution. The photon-counting system demonstrated the lowest average MGD. The GE Healthcare and Hologic flat-panel detector systems demonstrated a small but statistically significant dose difference. The pre-exposure dose contribution did not exceed 13% of the total exposure dose for any system in the survey. A comparison of the system calculated organ dose estimate from each machine with the corresponding MGD calculated from medical physics measurements indicated reasonably accurate organ dose estimates for most systems in the survey. Conclusion: The results of this study provide a comprehensive assessment of the breast dose performance of current digital mammography systems in a clinical screening setting. [ABSTRACT FROM AUTHOR]

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant, multisystem disorder that manifests with a spectrum of disease including cardiopulmonary complications. HHT is characterised by aberrant signalling via the transforming growth factor β (TGFβ) pathway, with loss of vascular integrity, angiogenesis and vascular dysplasia. The disease has an estimated prevalence of 1 in 5000 persons and the penetrance increases with increasing age. HHT commonly presents with epistaxis and telangiectasia, while visceral arteriovenous malformations are not uncommon. Mutations in the ENG, ACVRL1 and MADH4 genes account for 97% of all HHT cases, and it is recommended that genetic tests are used in combination with the clinical Curaçao criteria to confirm the diagnosis. HHT can be complicated by significant pulmonary vascular disease including pulmonary arteriovenous malformations, pulmonary arterial hypertension and high output cardiac failure. These are associated with substantial morbidity and mortality and therefore timely diagnosis is important to mitigate complications and optimise preventative strategies. This article outlines important advances in our understanding of the pathobiology of HHT and current recommendations regarding the diagnosis and screening of HHT with a specific focus on adult patients with pulmonary vascular disease. Important therapeutic advances, novel therapies on the horizon and unmet needs are also explored., Competing Interests: Dr Sarah Cullivan has no conflicts of interest in relation to this article. Dr Barry Kevane has no conflicts of interest in relation to this article. Dr Brian McCullagh has received supports for attending meetings from Janssen Pharmaceuticals, and has no conflicts of interest in relation to this article. Prof Terry O'Connor has no conflicts of interest in relation to this article. Prof Robin Condliffe has received honoraria for speaking and advisory boards from Janssen, and has no conflicts of interest in relation to this article. Prof Sean Gaine has received honoraria and speaker's fees from Actelion and Janssen Pharmaceuticals, outside the submitted work; received travel support from Actelion andJanssen Pharmaceuticals and ATAVANT, outside the submitted work; participated in a DSMB for Actelion and Janssen Pharmaceuticals, and is an advisory board member for ATAVANT, Bio Gossamer, and United Therapeutics, outside the submitted work., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Exercise training is recommended for pulmonary hypertension (PH). Post hoc analysis of the PH and Home-Based (PHAHB) trial stratified patients into two groups based on median diffusing capacity of the lungs for carbon monoxide (DLCO). Patients with higher DLCO had a greater improvement in physical activity performance in response to exercise training, compared to those with lower DLCO. DLCO may be an important consideration in prescribing exercise in PH., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: Pulmonary hypertension (PH) is a heterogeneous condition, associated with a high symptom burden and a substantial loss of exercise capacity. Despite prior safety concerns regarding physical exertion, exercise training as a supportive therapy is now recommended for PH patients. Currently, most programmes are hospital-based, which limits accessibility. There is a need to provide alternative approaches for physical activity engagement for PH patients. The aim of this research was to develop, implement and evaluate the safety, feasibility and effectiveness of home-based physical activity intervention for PH., Methods: An entirely remotely delivered home-based physical activity intervention underpinned by behaviour change theory and informed by end-users, was assessed using a single-arm feasibility study design. Participants (n=19; 80% female) with a mean±sd age of 49.9±15.9 years with a diagnosis of PH undertook a 10-week, home-based physical activity intervention with induction training, support materials, telecommunication support, health coaching, exercise training and assessments, all remotely delivered. Training involved respiratory training along with a combination of aerobic and resistance exercises., Results: The intervention was deemed safe as no adverse events were reported. A high level of feasibility was demonstrated as the protocol was implemented as intended, sustained a high level of engagement and adherence and was well accepted by participants in terms of enjoyment and utility. There was a significant improvement in functional capacity, physical activity, exercise self-efficacy and quality of life, between baseline and post-training., Conclusion: The study demonstrates that an entirely remotely delivered home-based physical activity programme is safe, feasible and effective in improving functional capacity, physical activity and quality of life in PH patients., Competing Interests: Conflict of interest: B. Kehoe's institution has received grant funding for the submitted research from Actelion Pharmaceuticals. B. Kehoe has received grant funding from the National Cancer Control Programme and Irish Research Council, outside the work submitted. Conflict of interest: S. Gaine's institution has received grant funding for the submitted research from Actelion Pharmaceuticals. S. Gaine has received honoraria and speaker's fees from MSD and Janssen Pharmaceuticals, outside the submitted work; received travel support from MSD and Janssen Pharmaceuticals, outside the submitted work; participated in a data safety monitoring board for United Therapeutics and Janssen Pharmaceuticals; and has received consulting fees from or Altavant, Gossamer Bio, Janssen and MSD outside the submitted work. Conflict of interest: B. McCullagh has received honoraria, speaker's fees and travel support from Janssen Pharmaceuticals, outside the submitted work. Conflict of interest: N.M. Moyna's institution has received grant funding for the submitted research from Actelion Pharmaceuticals. N.M. Moyna has received grants from Enterprise Ireland and Health Service Executive, outside the submitted work; and received consulting fees from Irish Health Life, outside of the submitted work. Conflict of interest: All other authors have nothing to disclose., (Copyright ©The authors 2024.)

Background: Strategies to reduce antibiotic overuse in hospitals depend on prescribers taking decisions to stop unnecessary antibiotic use. There is scarce evidence for how to support these decisions. We evaluated a multifaceted behaviour change intervention (ie, the antibiotic review kit) designed to reduce antibiotic use among adult acute general medical inpatients by increasing appropriate decisions to stop antibiotics at clinical review., Methods: We performed a stepped-wedge, cluster (hospital)-randomised controlled trial using computer-generated sequence randomisation of eligible hospitals in seven calendar-time blocks in the UK. Hospitals were eligible for inclusion if they admitted adult non-elective general or medical inpatients, had a local representative to champion the intervention, and could provide the required study data. Hospital clusters were randomised to an implementation date occurring at 1-2 week intervals, and the date was concealed until 12 weeks before implementation, when local preparations were designed to start. The intervention effect was assessed using data from pseudonymised routine electronic health records, ward-level antibiotic dispensing, Clostridioides difficile tests, prescription audits, and an implementation process evaluation. Co-primary outcomes were monthly antibiotic defined daily doses per adult acute general medical admission (hospital-level, superiority) and all-cause mortality within 30 days of admission (patient level, non-inferiority margin of 5%). Outcomes were assessed in the modified intention-to-treat population (ie, excluding sites that withdrew before implementation). Intervention effects were assessed by use of interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed by use of meta-regression. This trial is completed and is registered with ISRCTN, ISRCTN12674243., Findings: 58 hospital organisations expressed an interest in participating. Three pilot sites implemented the intervention between Sept 25 and Nov 20, 2017. 43 further sites were randomised to implement the intervention between Feb 12, 2018, and July 1, 2019, and seven sites withdrew before implementation. 39 sites were followed up for at least 14 months. Adjusted estimates showed reductions in total antibiotic defined daily doses per acute general medical admission (-4·8% per year, 95% CI -9·1 to -0·2) following the intervention. Among 7 160 421 acute general medical admissions, the ARK intervention was associated with an immediate change of -2·7% (95% CI -5·7 to 0·3) and sustained change of 3·0% (-0·1 to 6·2) in adjusted 30-day mortality., Interpretation: The antibiotic review kit intervention resulted in sustained reductions in antibiotic use among adult acute general medical inpatients. The weak, inconsistent intervention effects on mortality are probably explained by the onset of the COVID-19 pandemic. Hospitals should use the antibiotic review kit to reduce antibiotic overuse., Funding: UK National Institute for Health and Care Research., Competing Interests: Declaration of interests MJL, DWC, LY, TEAP, and ASW declare funding from the National Institute for Health Research (NIHR) for the ARK-Hospital programme. ASW is an NIHR Senior Investigator. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Physical activity (PA) is an established adjunct therapy for pulmonary hypertension (PH) patients to mitigate PH symptoms and improve quality of life. However, PA engagement within this population remains low. This study investigated PH patients' knowledge of PA, recalled advice, exercise preferences and PA support needs., Methods: Semi-structured interviews were conducted with 19 adults (mean age 50 years; SD ±12 years) diagnosed with PH, living in Ireland. Interview scripts were digitally recorded and transcribed verbatim. Thematic analysis was used to analyse the data., Results: Four key themes were identified: Lack of PA knowledge; exercise setting preference; accountability and monitoring; and clinician delivered PA information and guidance., Conclusion: This study found that PH clinicians provide suboptimal PA advice, yet patients desired clinician-delivered PA guidance. Home-based exercise was preferred with monitoring and external accountability deemed as important to facilitate sustained engagement., Practice Implications: PH clinicians are well positioned to play a critical role in assisting and empowering PH patients to engage in PA. Providing training and education to PH clinicians regarding exercise prescription may be beneficial. Further research is needed to evaluate the feasibility and efficacy of home-based exercise interventions to improve quality of life and physical activity in PH., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 McCormack et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Pulmonary hypertension (PH) is a progressive disease of the pulmonary vasculature, which is characterised by premature morbidity and mortality. The aim of this study is to define the characteristics of PH in the national PH unit (NPHU) in Ireland between 2010 and 2020., Methods: Cases of PH which were referred to the NPHU between 2010 and 2020 were included. PH was defined as a mean pulmonary artery pressure ≥25 mm Hg at right heart catheterisation., Results: Four hundred and fifteen cases of PH were identified during the study period. Group 1 pulmonary arterial hypertension (PAH) accounted for 39% (n=163) of cases, with a calculated annual incidence of 3.11 per million population (95% CI 1.53 to 4.70). The leading PAH subgroup was connective tissue disease-associated PAH (CTD-PAH), which was responsible for 49% of PAH referrals. This was followed by idiopathic PAH, with an estimated annual incidence of 0.63 cases per million population. The mean age at PAH diagnosis was 56±15 years and 86% (n=111) received double-combination or triple-combination therapy within the first 12 months of diagnosis. The 1-year, 3-year and 5-year transplant-free survival for PAH was 89%, 75% and 65%. This was significantly lower for individuals with CTD-PAH relative to other PAH subgroups (p<0.05)., Discussion: This study describes the incidence and outcomes of PH in Ireland. While the outcomes are comparable to other centres, the incidence of PAH and specific subgroups appears low, suggesting that improved disease awareness and case recognition are required. Furthermore, the survival of individuals with CTD-PAH is poor and requires additional exploration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hypercoagulability and endothelial dysfunction are hallmarks of coronavirus disease 2019 (COVID-19) and appear to predict disease severity. A high incidence of thrombosis despite thromboprophylaxis is reported in patients with moderate to severe COVID-19. Recent randomized clinical trials suggest that therapeutic-intensity heparin confers a survival benefit in moderate-severity COVID-19 compared to standard-intensity heparin, potentially by harnessing heparin-mediated endothelial-stabilizing and anti-inflammatory effects., Objective: We hypothesized that patients with moderate-severity COVID-19 exhibit enhanced hypercoagulability despite standard-intensity thromboprophylaxis with low molecular weight heparin (LMWH) compared to non-COVID-19 hospitalized patients., Methods: Patients with moderate COVID-19 and a control group (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]-negative hospitalized patients) receiving LMWH thromboprophylaxis were recruited. Markers of endothelial damage and plasma thrombin generation parameters were assessed., Results: Tissue plasminogen activator levels were significantly increased in the COVID-19 group (8.3 ± 4.4 vs. 4.9 ± 2.4 ng/ml; P = .02) compared to non-COVID-19-hospitalized patients. Despite thromboprophylaxis, mean endogenous thrombin potential was significantly increased among COVID-19 patients (1929 ± 448 vs. 1528 ± 460.8 nM*min; P = .04) but lag time to thrombin generation was significantly prolonged (8.1 ± 1.8 vs. 6.2 ± 1.8 mins; P = .02). While tissue factor pathway inhibitor (TFPI) levels were similar in both groups, in the presence of an inhibitory anti-TFPI antibody, the difference in lag time between the groups was abrogated., Conclusions: Collectively, these data demonstrate that COVID-19 of moderate severity is associated with increased plasma thrombin generation and endothelial damage, and that hypercoagulability persists despite standard LMWH thromboprophylaxis. These findings may be of clinical interest given recent clinical trial data which suggest escalated heparin dosing in non-severe COVID-19 may be associated with improved clinical outcomes., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

This case of progressive dyspnoea in a 43-year-old with idiopathic non-cirrhotic portal hypertension highlights important pulmonary vascular complications of chronic liver disease https://bit.ly/3rwEkhP., Competing Interests: Conflict of interest: S. Cullivan is the Janssen Pharmaceuticals Newman Fellow in pulmonary hypertension and translational medicine. Janssen Pharmaceuticals had no input in the submitted work and no funding was received for same. B. McCullagh has nothing to disclose. S. Gaine has received honoraria and speaker's fees from Actelion and Janssen Pharmaceuticals, and is an advisory board member for United Therapeutics, outside the submitted work., (Copyright ©ERS 2022.)

Pulmonary hypertension is a progressive cardiorespiratory disease that is characterized by considerable morbidity and mortality. While physical activity can improve symptoms and quality of life, engagement in this population is suboptimal. The aim of this study was to explore attitudes towards exercise and the dimensions that influence physical activity participation in individuals with pulmonary hypertension. Virtual, semi-structured interviews were conducted with individuals, with a formal diagnosis of pulmonary hypertension. Participants were recruited through the Pulmonary Hypertension Association of Ireland. Interviews were transcribed and analysed using thematic analysis. Nineteen patients were interviewed (n = 19). There was a female preponderance (n = 13) and the mean age was 50 ± 12 years. Three themes were identified and included fear, perceived value of exercise and environmental factors. Fear was the primary theme and included three sub-themes of fear of (i) over-exertion, (ii) physical damage and (iii) breathlessness. The perceived value of exercise encompassed two distinct sub-themes of perceived (i) exercise importance and (ii) benefits of exercise. Environmental factors included the terrain, weather conditions and location. Fear of overexertion, harm and dyspnoea strongly influenced attitudes to and engagement in physical activity. This study revealed heterogenous patient perspectives regarding the importance of physical activity and exercise. Future interventions that mitigate fear and promote the value of physical activity for individuals with pulmonary hypertension may have considerable benefits in promoting physical activity engagement. Such interventions require multidisciplinary involvement, including specialised pulmonary hypertension clinicians and exercise and behaviour change specialists., (© The Author(s) 2021.)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and under-recognised complication of acute pulmonary embolism. Information regarding the characteristics of CTEPH in Ireland is limited, and the aim of this retrospective cohort study was to address this knowledge gap. Seventy-two cases of CTEPH were diagnosed in the National Pulmonary Hypertension Unit (NPHU) in Ireland between 2010 and 2020. This accounted for 6% of all referrals to the unit and translates to an estimated annual incidence of 1.39 per million population (95% confidence interval, 0.33-2.46). The prevalence of diagnosed CTEPH in Ireland in 2020 was estimated at 12.05 per million population (95% CI 9.00-15.10). The average duration of symptoms prior to CTEPH diagnosis was 23 (±22) months. Patients with CTEPH were more likely to be male (n = 40, 56%), older (60 ± 17 years) and have identifiable risk factors for CTEPH (n = 61, 85%) at diagnosis. Regarding treatment, pulmonary hypertension (PH) vasodilator therapy was prescribed in 75% (n = 54) within 12 months of diagnosis, inferior vena cava filters were placed in 24% (n = 17) and 97% (n = 70) of cases were anticoagulated. Pulmonary endarterectomy was performed in 35% (n = 25), balloon pulmonary angioplasty in 6% (n = 4). One-, three- and five-year survival was 93%, 80% and 65% from the time of diagnosis, and this was significantly better in patients who underwent pulmonary endarterectomy (p = 0.01). This is the first study describing the characteristics of CTEPH in Ireland and highlights suboptimal disease recognition and referral for the assessment for pulmonary endarterectomy., (© The Author(s) 2021.)

We examined virus genomic evolution in an immunocompromised patient with prolonged severe acute respiratory syndrome coronavirus 2 infection. Genomic sequencing revealed genetic variation during infection: 3 intrahost mutations and possible superinfection with a second strain of the virus. Prolonged infection in immunocompromised patients may lead to emergence of new virus variants.

To date, coronavirus disease 2019 (COVID-19) has affected over 100 million people globally. COVID-19 can present with a variety of different symptoms leading to manifestation of disease ranging from mild cases to a life-threatening condition requiring critical care-level support. At present, a rapid prediction of disease severity and critical care requirement in COVID-19 patients, in early stages of disease, remains an unmet challenge. Therefore, we assessed whether parameters from a routine clinical hematology workup, at the time of hospital admission, can be valuable predictors of COVID-19 severity and the requirement for critical care. Hematological data from the day of hospital admission (day of positive COVID-19 test) for patients with severe COVID-19 disease (requiring critical care during illness) and patients with non-severe disease (not requiring critical care) were acquired. The data were amalgamated and cleaned and modeling was performed. Using a decision tree model, we demonstrated that routine clinical hematology parameters are important predictors of COVID-19 severity. This proof-of-concept study shows that a combination of activated partial thromboplastin time, white cell count-to-neutrophil ratio, and platelet count can predict subsequent severity of COVID-19 with high sensitivity and specificity (area under ROC 0.9956) at the time of the patient's hospital admission. These data, pending further validation, indicate that a decision tree model with hematological parameters could potentially form the basis for a rapid risk stratification tool that predicts COVID-19 severity in hospitalized patients., Competing Interests: HA, JC, and ED were employed by company SAS Institute LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Szklanna, Altaie, Comer, Cullivan, Kelliher, Weiss, Curran, Dowling, O'Reilly, Cotter, Marsh, Gaine, Power, Lennon, McCullagh, Ní Áinle, Kevane and Maguire.)

Selexipag is an oral selective prostacyclin-receptor agonist that was approved for use in patients with World Health Organisation (WHO) functional class II-III pulmonary arterial hypertension (PAH). Treatment with individualised doses of selexipag resulted in significant reductions in the composite end point of death or a complication related to PAH in the phase III GRIPHON (Prostacyclin [PGI2] Receptor Agonist In Pulmonary Arterial Hypertension) study. In order to better understand the real-world approach to selexipag titration and to establish the individualised maintenance regimens used in our centre, we performed this retrospective study of the first 20 patients prescribed selexipag. Baseline characteristics differed from the GRIPHON study, with more combination therapy and comorbidities at drug initiation. Maintenance doses were stratified as low-dose in 10% (n=2), medium-dose in 70% (n=14) and high-dose in 20% (n=4). This study highlights that selexipag can be safely initiated, titrated and transitioned in an outpatient setting to achieve an individualised dosing regimen., Competing Interests: Conflicts of interest None declared., (Copyright © 2021 Medinews (Cardiology) Limited.)

Pulmonary arterial hypertension is a rare disease of the pulmonary vasculature, characterised pathologically by proliferation, remodelling and thrombosis in situ . Unfortunately, existing therapeutic interventions do not reverse these findings and the disease continues to result in significant morbidity and premature mortality. A number of haematological derangements have been described in pulmonary arterial hypertension which may provide insights into the pathobiology of the disease and opportunities to explore new therapeutic pathways. These include quantitative and qualitative platelet abnormalities, such as thrombocytopaenia, increased mean platelet volume and altered platelet bioenergetics. Furthermore, a hypercoagulable state and aberrant negative regulatory pathways can be observed, which could contribute to thrombosis in situ in distal pulmonary arteries and arterioles. Finally, there is increasing interest in the role of extracellular vesicle autocrine and paracrine signalling in pulmonary arterial hypertension, and their potential utility as biomarkers and novel therapeutic targets. This review focuses on the potential role of platelets, extracellular vesicles and coagulation pathways in the pathobiology of pulmonary arterial hypertension. We highlight important unanswered clinical questions and the implications of these observations for future research and pulmonary arterial hypertension-directed therapies., (© The Author(s) 2021.)

Introduction: Novel therapies for pulmonary hypertension (PH) have improved survival and slowed disease progression. However, patients still present with symptoms of exertional dyspnoea and fatigue, which impacts their ability to perform activities of daily living, reduces exercise tolerance and impairs their quality of life (QoL). Exercise training has shown to be safe and effective at enhancing QoL and physical function in PH patients, yet it remains an underused adjunct therapy. Most exercise training for PH patients has been offered through hospital-based programmes. Home-based exercise programmes provide an alternative model that has the potential to increase the availability and accessibility of exercise training as an adjunct therapy in PH. The purpose of this study is to investigate the feasibility, acceptability, utility and safety of a novel remotely supervised home-based PH exercise programme., Methods: Single arm intervention with a pre/post comparisons design and a follow-up maintenance phase will be employed. Eligible participants (n=25) will be recruited from the Mater Misericordiae University Hospital PH Unit. Participants will undergo a 10-week home-based exercise programme, with induction training, support materials, telecommunication support and health coaching sessions followed by a 10-week maintenance phase. The primary outcomes are feasibility, acceptability, utility and safety of the intervention. Secondary outcomes will include the impact of the intervention on exercise capacity, physical activity, strength, health-related QoL and exercise self-efficacy., Ethics and Dissemination: Ethics approval has been obtained from the Mater Misericordiae Institutional Review Board REF:1/378/2032 and Dublin City University Research Ethics DCUREC/2018/246. A manuscript of the results will be submitted to a peer-reviewed journal and results will be presented at conferences, community and consumer forums and hospital research conferences., Trial Registration Number: ISRCTN83783446; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mediastinal adenopathy, septal line thickening, centrilobular ground glass opacities on CT and a markedly reduced T LCO in a young patient with pulmonary hypertension, should alert the clinician to this potential diagnosis https://bit.ly/3cfe9pX., Competing Interests: Conflict of interest: S. Cullivan is the Janssen Pharmaceutical Newman Fellow in Pulmonary Hypertension and Translational Medicine, this has no implications for the submitted work. Conflict of interest: J. Morris has nothing to disclose. Conflict of interest: C. McCormack has received funding from Janssen Pharmaceuticals for PhD in pulmonary hypertension and exercise training, this has no implications for the submitted work. Conflict of interest: A. Alameeri has nothing to disclose. Conflict of interest: S.P. Gaine has received honoraria and speaker's fees from Actelion and Janssen Pharmaceuticals, and is an advisory board member for United Therapeutics, outside the submitted work. Conflict of interest: B. McCullagh has nothing to disclose., (Copyright ©ERS 2021.)

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected over 30 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Therefore, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and nonsevere COVID-19. An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with nonsevere disease (not requiring intensive care), general medical in-patients without COVID-19, and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. We demonstrated that routine clinical blood parameters including increased mean platelet volume (MPV) and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit (ICU) admission. Strikingly, agonist-induced ADP release was 30- to 90-fold higher in COVID-19 patients compared with hospitalised controls and circulating levels of platelet factor 4 (PF4), soluble P-selectin (sP-selectin), and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and nonsevere COVID-19. Moreover, we have determined all COVID-19 patients possess hyperactive circulating platelets. These data suggest abnormal platelet reactivity may contribute to hypercoagulability in COVID-19 and confirms the role that platelets/clotting has in determining the severity of the disease and the complexity of the recovery path., Competing Interests: The authors have declared that no competing interests exist.