Sharing the knowledge and expertise of BSH members throughout the global Haematology community

'BSH Global Speakers' was established in 2015 as a core project of the BSH Global Haematology Special Interest Group (SIG). As the project enters its eighth year, we present an update and reflection on the successes and challenges encountered. Initially known as the 'Plenary Speaker Scheme', the project was developed following a stakeholder meeting in 2015 at the inception of the SIG. Haematology colleagues from the UK and low-and middle-income countries (LMIC) came together to discuss how the BSH may be best placed to support haematologists practicing in LMICs. Sharing of expertise and building collaborative networks were identified as key priorities. The 'Plenary Speaker Project' was conceived;BSH haematologists would be supported in delivering plenaries at the meetings of colleagues in LMICs, with the aim that each visit could act as a catalyst for creating networks and developing collaborative projects in education, research, and capacity building. We established a yearly cycle of inviting applications from LMIC societies for a funded speaker at their scientific meetings, selecting the most impactful meetings, then recruiting appropriate UK-based speakers. We place emphasis on the likelihood of ongoing collaborative working or other impacts, for example engagement with local haematology trainees. To date, ten speakers have represented BSH at the meetings of LMIC societies, presenting on diverse topics, from molecularly guided interventions to prevent relapse in AML, to adapting lymphoma treatment strategies for low resource settings. Recently we have opened applications to nurse specialists and scientists, with our first scientific speaker presenting in Thailand May 2023. The COVID-19 pandemic created significant challenges for the project due to the disruption in international travel and the cancellation of many haematology meetings around the globe. We were, however, able to adapt the project to support virtual speakers at meetings in South Africa, Vietnam, and Ghana. Although virtual meetings do not naturally lend themselves to collaborative working, we were pleased that a longer term joint educational program in haemoglobinopathy care has been established with the Vietnamese Society of Haematology as a result of BSH support. The impact of BSH Global Speakers is significant. Even at smaller meetings, speakers will have the ear of the majority of practicing haematologists in a country. From the relationships built between societies and speakers we have seen the development of fellowship programmes, online education programmes, laboratory support, and numerous networks for informal advice in clinical care, research, and more.

17th Annual Sickle Cell and Thalassaemia Conference

The proceedings contain 115 papers. The topics discussed include: clinical and genetic predictors of sickle cell nephropathy in Malawi;clinicohematological characteristics of iron deficiency anemia and hemoglobinopathies in Pakistan;an experience of non-hospital based laboratory;assessment of hematological parameters of petrol filling workers at petrol stations in Ethiopia: a comparative cross-sectional study;burden and risk factor to acute myocardial ischemia in children with sickle cell anemia;dyslipidemia in transfusion-dependent-thalassemia patients and its correlation with serum vitamin D level;impact of COVID-19 pandemic to pre-transfusion hemoglobin level and frequency of transfusion in transfusion-dependent thalassemia patients in Indonesia;retinopathy in Egyptian patients with sickle cell disease;and dietary pattern, socio-demographic characteristics and nutritional status of pregnant women attending Barau Dikko teaching hospital and the need to develop recommended dietary allowance and dietary reference intakes for sickle cell disease patients.

Prevalence of SARS-CoV-2 in hemoglobinopathies is modified by age and race.

Prior literature has established a positive association between sickle cell disease and risk of contracting SARS-CoV-2. Data from a cross-sectional study evaluating COVID-19 testing devices (n = 10,567) was used to examine the association between underlying health conditions and SARS-CoV-2 infection in an urban metropolis in the southern United States. Firth's logistic regression was used to fit the model predicting SARS-CoV-2 positivity using vaccine status and different medical conditions commonly associated with COVID-19. Another model using the same method was built using SARS-CoV-2 positivity as the outcome and hemoglobinopathy presence, age (<16 Years vs. ≥16 Years), race/ethnicity and comorbidities, including hemoglobinopathy, as the factors. Our first model showed a significant association between hemoglobinopathy and SARS-CoV-2 infection (OR: 2.28, 95 % CI: (1.17,4.35), P = 0.016). However, in the second model, this association was not maintained (OR: 1.35, 95 % CI: (0.72,2.50), P = 0.344). We conclude that the association between SARS-CoV-2 positivity and presence of hemoglobinopathies like sickle cell disease is confounded by race, age, and comorbidity status. Our results illuminate previous findings by identifying underlying clinical/demographic factors that confound the reported association between hemoglobinopathies and SARS-CoV-2. These findings demonstrate how social determinants of health may influence disease manifestations more than genetics alone.

Development of a Questionnaire on Access to Sickle Cell Disease Care in the Indigenous Tharu Population of Nepal

Purpose of Study Sickle cell disease (SCD) disproportionately affects the Tharu population of Nepal, a marginalized indigenous group concentrated in the Dang district. SCD is a structural hemoglobinopathy resulting in abnormal red blood cells with a tendency to occlude microvasculature. Since 2015, University of British Columbia medical students and a local community partner, Creating Possibilities, have improved access to SCD screening and diagnosis for the Tharu population. However, interviews conducted in 2016- 2017 found that SCD-afflicted community members encounter a number of challenges to obtain treatment once diagnosed. The purpose of this study was to develop a questionnaire on barriers to accessing SCD care in this community. Methods Used The Barriers to Accessing SCD Care Questionnaire was developed from items in existing scales, deductive and inductive item generation, and feedback from expert local partners. Reviewing literature on barriers to accessing healthcare in the Western region of Nepal informed region-specific questionnaire items, while literature on accessing SCD treatment in resource-limited settings informed SCD-specific questionnaire items. We also reviewed the literature on barriers to treatment for various stigmatized chronic health conditions in low-resource settings. Summary of Results Qualitative interviews with SCD-afflicted Tharu individuals in 2016-2017 identified inadequate local medical resources, transportation, financial strain, and limited awareness as barriers to care. Based on the literature review, we organized all survey items under the themes transportation, medical infrastructure, finances, community attitudes, and personal attitudes. The questionnaire includes closed-ended questions using a Likert scale, as well as open-ended interview prompts. It was made in collaboration with local community members to ensure it is culturally appropriate, needs-specific, and easily understandable. The questionnaire received ethics board approval, and interviews will begin once local health authorities lift COVID-19 restrictions. Conclusions Results from the Barriers to Accessing SCD Care questionnaire will guide future community-based interventions.

Access to Sickle Cell Disease Treatment in the Indigenous Tharu Population of Nepal

Purpose of Study: Sickle cell disease (SCD) is a hemoglobinopathy that disproportionately affects the indigenous Tharu population of Nepal, a marginalized ethnic group concentrated in the Dang district. There are significant global disparities in the prognosis of SCD;in low-income countries, which lack screening and management infrastructure, up to 80% of those born with SCD are undiagnosed and less than half survive beyond 5 years of age. Since 2015, University of British Columbia medical student teams have collaborated with a local community partner, Creating Possibilities (CP), to improve SCD awareness, screening, diagnosis, and management for the Tharu population in and around Dang. Community members with SCD have previously expressed numerous challenges in obtaining treatment once diagnosed. This study aims to better understand difficulties in accessing SCD care for this community. Methods Used: The Access to SCD Care Questionnaire was developed from items in existing scales, deductive and inductive item generation, and feedback from expert local partners to ensure it is culturally appropriate, needs-specific, and easily understandable. The questionnaire includes closed-ended questions using a Likert scale and open-ended interview prompts. It centers around five core themes: personal beliefs, community attitudes, finances, transportation, and medical infrastructure. Interviews were conducted in Tharu (local dialect) by CP staff members in January to March 2022. Themes and sub-themes were qualitatively analyzed. Summary of Results: Participants aged from 14 to 42 with an equal sex ratio, a total of 12 interviews were conducted before study saturation was reached. All participants reported at least one minor or major problem with access to SCD care in each of the five core themes of the questionnaire. Inadequate healthcare infrastructure was the most frequently reported barrier, with participants reporting lack of local medication accessibility and low supplies at further district hospitals. Additionally, despite government funding for treatment coverage, participants reported difficulties obtaining the necessary legal documents to prove eligibility. The second largest perceived barrier to care was transportation, which was reported to be costly, time-consuming, and not readily available. Regardless of sub-theme, participants reported that system-wide effects from COVID-19 perpetuated these issues. Conclusion(s): Results from the Access to SCD Care Questionnaire demonstrate that availability and accessibility to medications and transportation services are the primary challenges to receiving SCD care in this indigenous community. Therefore, future interventions for this community should focus on these findings. In contrast with previous literature, community stigma and personal beliefs were not often reported as hindering SCD treatment. This may be attributed to successful education campaigns within this specific community or due to participation bias.

Impact of COVID-19 on transfusion care of patients with hemoglobin disorders in India

As we navigate the first pandemic of our generation, we've been learning and adapting ourselves to this viral infection and its consequences. It's been more than two years since the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) pandemic, and the virus has crippled the healthcare services in almost all the countries of the world. The healthcare systems in various parts of the world are still in the phase of recovery from the effect of the pandemic, as each country is witnessing the emergence of various variants causing multiple waves of infection. As an important part of the health care system, blood banks were one of the affected services. Most of the blood centers in India reported a significant reduction in blood donation during the COVID-19 pandemic. As transfusion services constitute a crucial backbone for the management of transfusion-dependent patients with hemoglobinopathies, the substantial reduction in the timely blood supply drastically affected these patients. All major healthcare centers in India were designated as COVID-19 care centers, which left very few options for these patients to visit for their routine care. Every country managed this acute blood shortages and developed unique strategies to support patients requiring blood transfusion. This manuscript aims to provide a snapshot of the challenges faced by the blood banks and transfusion services in India in the care of patients with hemoglobinopathies, and the mitigation strategies that were adopted.Copyright © Annals of Blood. All rights reserved.

The Burden of Sickle Cell Disease in Saudi Arabia: A Single-Institution Large Retrospective Study.

Purpose: Sickle cell disease (SCD) is a significant burden for patients and healthcare systems due to multiple factors, including high readmission rates. This study aimed to determine the general characteristics, etiology of admissions, annual admission rate, length of stay, and readmission rate of patients with SCD. Patients and Methods: This retrospective observational study included all adult patients with SCD admitted to the General Internal Medicine (GIM) unit between 2016 and 2021. Results: There were 160 patients (mean age, 31.08 ± 9.06 years; 51.25% female) with SCD included in this study. Most originated from southern Saudi Arabia (45.62%). The average annual number of emergency department (ED) visits was 4, and approximately 19% of patients had ≥3 annual admissions. The mean length of stay was 6 days. The readmission rates at 7, 30, 60, and 90 days were 8%, 24.5%, 13.6%, and 10.8%, respectively. Conclusion: SCD generates a significant economic burden on the Saudi society and the effects on the healthcare system and patients' quality of life are evident in the high ED visits, readmission rates and prolonged hospitalization. Thereupon we advocate the implementation of sickle cell disease-specialized multidisciplinary clinics.

Kidney Transplantation in a Patient Affected by Sickle Cell Trait: A Case Report and State-of-the-Art Review.

Chronic kidney disease (CKD) is a common feature of sickle cell disease (SCD). The awareness of the clinical presentation and renal involvement in patients affected by hemoglobinopathies is greatly needed. Patient management is particularly complex, especially with kidney transplantation. We, therefore, report the case of a 56-year-old patient affected by sickle cell trait who underwent kidney transplantation. This case will underline all the various challenges the nephrologist must face in this clinical setting and their management.

Are there racial disparities in the incidence of venous thromboembolism (VTE) in hospitalized cancer patients with COVID-19?

Background: Both cancer and COVID-19 have been reported to be associated with an increased risk of VTE. Severe disease needing hospitalization is also associated with an increased risk of VTE. There is a paucity of data evaluating the effects of race on this risk, with the limited available data suggesting that such a correlation exists. Given the increased prevalence of comorbidities and risk factors for VTE in African Americans (AA), we sought to evaluate if there are racial disparities in the incidence of VTE in the hospitalized subset of COVID-19 patients with cancer. Method(s): This was a retrospective chart review of unvaccinated cancer patients hospitalized with COVID-19 at a major tertiary health facility. Only cancer patients who were on active systemic chemotherapy were included. The primary study outcomes were development of DVT or PE (VTE) within 30 days of COVID-19 diagnosis. Secondary outcomes included mortality, hospital length of stay, mechanical ventilation, ICU admission, and need for vasopressors. Mean and standard deviation were reported for continuous variables;proportions were reported for categorical variables. To compare between races, the Chi-square test was used for categorical variables and the t-test was used for continuous variables. Multivariable logistic regression was then conducted to assess the relationship between race and selected factors. All statistical tests were 2-sided with an alpha (significance) level of 0.05. Result(s): A total of 73 patients were included in our analysis. The median age of the cohort was 70 years (interquartile range [IQR] 64-79). Gender breakdown: 58.9% males, 41.1 females. 31.5% were Caucasian, 64.4% African American, 1.4% Hispanic, and 2.7% other races/ethnicities. There were 8 DVT/PE patients in the cohort. Of 23 Caucasians in our cohort, 3 (13.0%) had VTE. Of 47 African Americans, 5 (10.6%) had DVT/PE. There was no significant difference between the incidence of VTE and race (p > 0.05). Multivariable logistic regression did not show a significant relationship between race and VTE, controlling for age, ICU stay, intubation, vasopressor use, serum ferritin and serum IL-6 levels. Notably, all patients included in this study were on enoxaparin prophylaxis for VTE. The only variable associated with DVT/PE was age and the presence of hemoglobinopathy. Incidence of VTE was significantly associated with increasing age (p < 0.03) and the presence of hemoglobinopathy (p < 0.01). Hemoglobinopathy was only seen in AA cancer patients with VTE (n = 4), and none in Caucasian patients. Conclusion(s): Contrary to what has been reported in the literature, we did not detect racial disparity in the incidence of VTE in hospitalized cancer patients with COVID 19. Prophylactic anticoagulation likely had a protective effect. However, racial disparity was observed in AA cancer patients with hemoglobinopathy with increased VTE risk despite prophylactic anticoagulation. This warrants further evaluation in future studies.

Haematology audit of 801 COVID-19 patients' basics and beyond- Prospective observational study.

Background and Objective: COVID-19 has become a major health concern since 2020. Its clinical presentation varies from asymptomatic cases to cases with respiratory failure needing ICU management. It has created a huge burden on limited health care resources. We need better understanding of the pathogenesis and interplay between virus and other factors which decide outcome. We seek biomarkers to predict severe illness to offer better triaging of patients to provide hospital-based care to the patients at risk of severe illness. Material and Methods: We took 801 consecutive RT-PCR-positive COVID cases coming to our center. Their hematological work-up, such as complete blood count, peripheral smear, reticulocyte count, and G6PD activity, was tested. The pattern of hematological abnormalities was assessed across disease severity groups to identify predictors of severe illness from basic investigation. Also, the interplay between iron deficiency and possible hemoglobinopathy trait and COVID was explored. Results Discussion and Conclusion: We found old age, male gender, diabetes, neutrophilia, lymphopenia, monocytopenia, and eosinopenia at presentation to be associated with moderate to severe illness and may help in triaging with other inflammatory and radiological parameters. We found thrombocytosis rather than thrombocytopenia as a predictor of severe illness. Our preliminary findings suggest the need to explore the protective role of hemoglobinopathy traits and iron deficiency against severe COVID illness.

Telehealth and health outreach mode of healthcare delivery in patients with bleeding disorders: Experience from a Tertiary Care Centre during COVID-19 pandemic

Background: Telehealth and health outreach facilities evolved as an integral component of healthcare delivery during COVID-19 pandemic;digital healthcare tools such as Virtual Clinics (VCs) enterprise along with outreach facilities adapted for uninterrupted healthcare delivery. Pediatric Non-Malignant Blood Disorders (NMBDs) section at King Faisal Specialist Hospital and Research Centre, Riyadh is a tertiary referral center for patients with bleeding disorders. Aim(s): To maintain access to care facilitating comprehensive care through physician consults, laboratory investigations and blood products supply Methods: Ambulatory care visits amongst children (<=14 years) collected and dashboard created utilizing REDCap for tracking visits (in-person and virtual) during the pandemic (April'2020 to April'2022). Result(s): Total of 7610 visits on 4610 patients identified with 72% (5520) in-person and 27% (2100) virtual visits;increase in virtual visits by 328% (490 visits) observed while comparing 12 month period prior to the COVID-19 pandemic ;in-person visits decreased by 15% (6493 visits) with an overall increase of 10% in ambulatory care visits, indicative of substitutive care delivery mode. Majority of virtual visits observed amongst Hemoglobinopathies, 45%, Bone Marrow Failures, 36% and bleeding disorders, 19%;with an average of 2.0 virtual visits per patient observed. Amongst bleeding disorders majority of the cases were Hemophilia, 40% (87);Von Wille Brand, 30% (65);Rare bleeding disorders, 21% (46) and Glanzmann thrombasthenia 9% (21).Combination of telehealth and health outreach resulted in timely and uninterrupted laboratory result reviews, medication refills and dental referrals and factor-replacement products were delivered in collaboration with outreach -satellite pharmacies. Conclusion(s): In our experience, integrating telehealth in alliance with regional outreach facilities found effective in maintaining continuity of care, demonstrating an unexpected prospect in the face of adversity. We plan to continue virtual care to resolve patient access, clinician shortage and geographic disparities while supporting the National Healthcare Transformation Program driven by the Saudi Vision 2030.

Prevalence of short stature in transfusion dependent beta thalassemia patients in a tertiary care centre in North East India.

Background: beta thalassemia is one of the most common hereditary hemoglobinopathy requiring regular blood transfusion to help reduce the complications of anemia and allow normal growth in children. Materials and Methods: It was a cross-sectional study done on 50 numbers of transfusion dependent beta thalassemia patients between 18 months and 18 years of age in North east India. Growth parameters like weight, height, BMI were recorded. Results: Overall prevalence of stunting was 68%, a significant association was found between stunting and religious connotation.

CONSOLIDATION OF ERN-EUROBLOODNET: THE EUROPEAN REFERENCE NETWORK ON RARE HEMATOLOGICAL DISEASES FIRST 5 YEARS OF IMPLEMENTATION

Background: ERN-EuroBloodNet was established in 2017 as the European Reference Network on Rare Hematological Disorders (RHDs) bringing together nationally recognized centres of excellence with the goal of promoting EU best health care in RHDs. ERN-EuroBloodNet has been recently enlarged integrating 103 HCP from 24 EU-MS. Aims: ERN-EuroBloodNet was conceived to contribute to innovative, efficient and sustainable health systems and facilitate access to better and safer healthcare for EU citizens while decreasing the cross-border health barriers. Methods: Since 2017, ERN-EuroBloodNet established the state-of-the art of RHD allowing the implementation of transversal and disease-specific strategies, where actions on very rare RHD were prioritized. Results: Profile. 182 expert profiles were created freely accessible. Expert centers follow 65,000 RHD patients and treat 5,000 new patients per year, while 24 patients requested support for cross-border health assistance. Expertise. The need to improve access to next-generation sequencing for non-oncological RHD and bone marrow transplantation for sickle cell disease (SCD) was identified. Also, significant disparities in the clinical practice of primary vitreoretinal lymphoma were found and we demonstrated that less than 30% of children with SCD benefit from adequate annual stroke risk monitoring. Guidelines. A repository of 68 Clinical Practice Guidelines (CPG) classified on quality of evidence and consensus approach was created. Recommendations for diagnosis and treatment of methemoglobinemia was published in collaboration with EHA. A CPG on Adult Burkitt Lymphoma is under development. Next topics focus long-term complications in hemoglobinopathies and patients' pathways&summary. Education. ERN-EuroBloodNet Webinars were launched for professionals with 26 Thursdays Webinars and 3 EBAH accredited Topic on Focus on Cutaneous Lymphoma, Thrombotic Microangiopathies, and Bone Marrow Failures. A collaboration was established for EHA & ERN-EuroBloodNet Spotlight on Castleman Disease. For patients, 3 Topic on Focus were launched for Myelodysplastic syndromes, SCD, and Cutaneous lymphoma. Past webinars are available at EuroBloodNet EDU Youtube channel. Preceptorships on SCD will be launched soon. Telemedicine. 43 complex cases have been inter-professionally discussed in the Clinical Patient Management System with 21 outcome reports delivered. Registries. 184 Registries were identified through the European Rare Blood Diseases Platform (ENROL), endorsed by the EHA. The ENROL project, which includes rare anemias, dendritic cell leukemia and von Villebrand's disease pilots, aims to collect exhaustive and therefore epidemiological data for RHDs. The final objective is a possibility of EU health planningl and the promotion of research by identifying cohorts of patients. ERNEuroBloodNet launched the collaborative platform on patients with red blood cells and COVID-19 containing so far 373 patients. Collaborations. collaborative research projects were encouraged like EC-funded projects i.e., genomics and personalized medicine in hematological diseases (GenoMed4All) and the properties and viability of erythrocytes (EVIDENCE), or the International Hemoglobinopathy Research Network (INHERENT) for genomic and phenotypic correlations. Summary/Conclusion: The implementation of well-defined strategies but above all adapted to the specific and not yet covered needs of RHD has led to the realization of concrete projects. This has laid the foundations to strengthen health systems in the field of RHD and allow them to flourish under the new EU4Health programme.

The significance of antiglobulin (Coombs) test reactivity in patients with COVID-19.

Previous case reports have described patients with COVID-19-associated autoimmune hemolytic anemia (AIHA), and cold agglutinin disease (CAD) which is characterized by a positive direct antiglobulin (DAT) or "Coombs" test, yet the mechanism is not well understood. To investigate the significance of Coombs test reactivity among COVID-19 patients, we conducted a retrospective study on hospitalized COVID-19 patients treated at NMC Royal Hospital between 15 April and 30 May 2020. There were 27 (20%) patients in the Coombs-positive group and 108 (80%) in the Coombs-negative group. The cold agglutinin titer was examined in 22 patients due to symptoms suggestive of cold agglutinin disease, and all tested negative. We demonstrated a significant association with reactive Coombs test results in univariate analysis through clinical findings such as ICU admission rate, the severity of COVID-19, and several laboratory findings such as CRP, D-dimer, and hemoglobin levels lactate dehydrogenase, and RDW-CV. However, only hemoglobin levels and disease severity had a statistically significant association in multivariate analysis. A possible explanation of COVID-19-associated positive Coombs is cytokine storm-induced hyperinflammation, complement system activation, alterations of RBCs, binding of SARS-CoV-2 proteins to hemoglobin or its metabolites, and autoantibody production. Coombs-positive patients were tested for hemolysis using indirect bilirubin, consumed haptoglobin, and/or peripheral smear that ruled out any evidence of hemolysis. Understanding this etiology sheds new light on RBC involvement as a pathophysiological target for SARS-CoV-2 by interfering with their function; consequently, therapies capable of restoring RBC function, such as erythrocytapheresis, could be repurposed for the treatment of worsening severe and critical COVID-19.

MANAGEMENT OF SICKLE CELL DISEASE: A CLINICAL PRACTICE SURVEY

Background: Therapeutic options for Sickle Cell Disease (SCD) have increased recently as well as the development of updated national guidelines. It is not known how these options are being offered or to what degree guidelines are incorporated into clinical practice. Objectives: To assess the clinical practice patterns of providers treating children with SCD. Design/Method: A survey study was performed which included nine sections: clinic structure, prophylaxis, immunizations, hydroxyurea, splenic sequestration, stroke, novel therapies, potential curative therapies, and transition. Survey was disseminated over a three-month period via SurveyMonkey, to members of the American Society of Pediatric Hematology-Oncology Hemoglobinopathy Special Interest Group. Results: There were 86 respondents;most were attending/faculty (85%, 73/86) who were part of a university/academic practice (65%, 56/86). Program size was most commonly 50-250 patients (44%, 37/86). Accessibility to support staff in clinic included 95% (81/86) social work;76% (65/86) child life;68% (58/86) nurse coordinator and 34% (29/86) school liaison and 15% (13/86) transition navigator. For preventive care, 72% prescribe penicillin prophylaxis before 2 months of age recommending 100% (83) for HbSS and Sβnull, 72% (60/83) for HbSC and 70% (58/83) for HbSβplus. Influenza was the most common vaccine offered in clinic at 96% (76/79) with 91% (72/79) offering pneumococcal vaccines, 84% (67/79) offering meningococcal vaccines and 50% (40/79) offering COVID vaccines. Transcranial doppler screening was offered in 95% (69/73) but only 42% (31/73) performed MRI screening for silent stroke. Transfusion therapy was recommended for primary stroke prevention by 90% (65/72) and 84% (59/70) attempt to transition to hydroxyurea following TWITCH guidelines. For secondary stroke prevention, 88% (63/72) recommend chronic transfusion therapy. Regarding disease-modifying therapy, 90% (70/78) report starting hydroxyurea routinely in patients with HbSS and Sβnull;initiated at 9 months of age by 69% (54/78). Laboratory monitoring recommended every 3 months for stable dosing by 62% (49/78) and hydroxyurea held by 56% (44/78) if platelets <75,000, 73% (56/78) for neutrophils <1000. New therapies were recommended for patients on hydroxyurea who were still experiencing SCD complications: L-glutamine 68% (37/54;crizanlizumab 93% (54/58). Voxelotor was recommended for patients on hydroxyurea with low hemoglobin 65% (43/66). Matched sibling transplant was considered for any disease severity by 55% (38/69). Gene therapy trial is offered on-site by 29% (20/69). Transition programs were endorsed by 61% (42/69), but only 45% (31/68) had dedicated staff. Conclusion: This survey is the only assessment of the application of SCD guidelines in clinical practice.

Digital AI in hematology-integration of the scopio labs x100 scanner with newly implemented AI capabilities into routine clinical work flow

BACKGROUND Digital pathology and artificial intelligence (AI) are areas of growing interest in pathology. A number of institutes have already integrated digital imaging into routine workflow, relying on AI algorithms for the detection of various cancers and mitotic activity quantification. Despite the use of whole slide imaging (WSI) for tissue evaluation, the field of hematology has lagged behind. While many hospitals rely on limited technologies for automated peripheral blood evaluation (e.g. CellavisionTM), the Scopio LabsTM X100 digital scanner provides high resolution oil-immersion level dynamic images of large scanned areas (https://scopiolabs.com/hematology/). With recent FDA-clearance and newly implemented AI capabilities, the Scopio Labs scanner allows for clear and accurate cytomorphologic characterization and cell quantification for peripheral blood smears (PBS). To this end, we aimed to be one of the few pioneering institutes in the United States to adopt early and implement this technology into our routine workflow as a 'hub and spoke' model for optimized case assessment, data sharing and result reporting across multiple satellite locations within our hospital health system. DESIGN A Scopio x100 digital scanner was deployed at our main hospital site, with an anticipated secondary scanner for installment at a satellite laboratory. PBS flagged for hematopathologist review from two satellite laboratories were scanned, and full-field digitalized slides were evaluated by hematopathologists following AI automated analyses. RESULTS 311 peripheral smears were scanned since April 2021 and representative slides were digitalized at 100x magnification (Figure 1, weblink: https://demo.scopiolabs.com/#/view-scan/9231acaf-f898-4649-950d-a41c26c2baaa) with rapid monolayer, monolayer, fullfield, and full-field cytopenia scan options available. The automated AI capabilities classified cells into lineage-specific categories with quantification based on cytomorphologic features (Figure 2). Other AI features include additional cell assignment, cell annotation and comments accessible to all users, finalized report PDF generation, export, upload into our current PowerPath TM software with linkage to the corresponding flow cytometry and bone marrow biopsy reports;and the ability to share digitalized slides with clinicians, laboratory personnel and trainees using uniquely generated weblinks. Images can be used for lectures and tumor boards. Additionally, an 80-case study set for PBS was created for medical students, residents and fellow teaching purposes, including cases displaying acute B-cell lymphoblastic leukemia (B-ALL), acute myelomonocytic leukemia (AMML), hypersegmented neutrophils in COVID-19(+) patients, myelodysplastic syndrome (MDS), atypical lymphocytes, hemoglobinopathies, platelet disorders and various lymphomas. Overall improvements were made to the following areas: CLINICAL WORK/DIAGNOSIS 1. Time-saving due to pre-categorization of cells into lineage-specific groups for pathologist review 2. Minimizes subjectivity in cell counting and cellularity assessment EDUCATION 1. Case-based collection with flow and molecular being maintained here 2. Efficient case retrieval with retained annotations/comments for teaching purposes 3. Wide array of digitalized images for hematology atlas and publications ARCHIVING 1. Collection of reference images (intra/inter departmental) for an array of morphological entities for clinical reference and refined diagnosis (e.g. Bethesda reference images for pap by ASC) 2. Digital catalogue for long-term case follow-up and retrospective review CONCLUSION The Scopio Labs X100 digital system provides an efficient and cost-effective web-based tool to streamline clinical workflow and enhance PBS evaluation. With its recent AI capabilities of cell quantification, lineage-assignment and report-generation, we aim to continue our efforts to fully integrate Scopio Labs into our routine daily clinical workflow for reviewing PBS specimens. CONFLICT OF INTEREST STATEMENT The authors have nothing to isclose with regard to the submitted work (Figure Presented).

Clinical chemistry and immunoassay test results: Harmonisation and standardization of discordant notes

However, it is this very set of tests that have come Hin question. First, what is the normal and acceptable range (upper & lower limits) of different Clinical Chemistry and Immunoassay biomarkers in a particular population has been debated in different scientific fora. This is because the level of markers can change in relation to other biochemicals, biomolecules and hormones, which themselves vary considerably with race, gender, age, different physiological conditions (like pregnancy, new-born) and other illnesses & interfering substances. The variation can be to an extent that each individual can seem to have their own set-point of these parameters. A second problem which the diagnosticians have to grapple with is the variability of test-results in itself;even a broadly similar set of instruments and methods can provide variable results. It is then a real challenge to physicians, to decide whether the patient is suffering from a disease or not, since other factors can also cause changes in test levels. Standardization and harmonization of clinical chemistry and immunoassay testingis therefore still a formidable challenge, due to the lack of proper reference intervals and sometimes due to standardized measurement procedures. Laboratory medicine community the world over has realized that, variability in test results in different platforms can create a lot of confusion to clinicians and the general population;harmonization of procedures is therefore the need of the hour. In this talk, I will provide few examples and technical solutions to address laboratory challenges and to take it forward from both Clinical Chemistry as well as Immunoassay platforms. To begin with, harmonization and standardization of TSH and other thyroid function tests are still a formidable challenge, due to the lack of proper reference intervals and standardized measurement procedures. It has been documented that even a broadly similar set of instruments and methods can give up to 40% more or less values in TSH levels. Based on a particular population's demographic variations, reference interval can be different for immunoassay like TSH. Therefore, we have verified the reference interval for the Indian population for TSH in our laboratory. We have screened 800 subjects, of which 630 healthy subjects were chosen in the study group for reference interval verification. The reference interval (90% Confidence interval) for TSH by non-parametric procedure (bootstrap) was 0.48- 4.52, and by parametric one (after transformation of the data) was 0.45-4.27 for the adult population, which is little different from the manufacturer's guidelines. Similarly, we have conducted a study of 2797 female patients and 2805 male patients in a six month period and have observed that, women have a greater risk of being 14% under-diagnosed of acute coronary syndrome, if we donot use gender specific cut off (Male: 32.3 pg/ml and Female: 14.6pg/ml for the Indian population), with high th sensitive troponin I assay near the 99 percentile of a reference control population. Therefore, implementation of sex-specific hs-cTnI assay was able to identify 14% of under-diagnosed women with ACS in 6 months period. This in turn also decreased the number of men being diagnosed by 3%. On a similar note, there has been a continuous challenge in the health care system in U.S, Europe and other countries to standardize and harmonize the HbA1c reporting: the decision on what to report in NGSP (%) and/or IFCC (mmol/mol) units along with eAG (in either mmol/L or mg/dL). This globalization places a responsibility on laboratory medicine specialists to work together to reduce the current variability in patient results, which arises from differences between units, methods and laboratory practices in different countries. Due to the standardization efforts of IFCC, NGSP, and also due to ongoing efforts of manufacturers and laboratories, the quality of HbA1c reporting has increased dramatically. Consequently, there has been a paradigm shift: HbA1c is now considered the gold standard, not only for monitoring, but also for diagnosis of diabetes. We have performed verification studies of HbA1c by different methods: HPLC, Capillary Electrophoresis, Enzymatic, Immunoassays in 200 samples and compared 60 samples with hemoglobinopathies. Finally, we have also explored harmonizing the clinical protocol based on the use of inflammatory and routine laboratory biomarkers in 2,654 COVID-19 patients. To explain the role of harmonizing routine laboratory parameters in disease monitoring, two adult males, two adult females and one adolescent girl were selected. These are representative examples of different manifestations of COVID 19, with Adult Respiratory Distress Syndrome (ARDS), Cardiac Injury, Neurological manifestations and Pediatric Multi system inflammatory syndrome (PIMS), admitted in the Intensive care unit (ICU) of the hospital, which will be discussed. Therefore, the road map for laboratory medicine will involve strategies for harmonizing, communicating and integrating with all stakeholders, like, clinicians, diagnosticians and IVD industry, in order to formulate guidelines for assisting in correct measurement, diagnosis and management of diseases.

Effects of Novel Coronavirus 2019 Infection on Antenatal Hematological Parameters in Pregnant Women

Background: Disturbance of haematological parameters is prevalent in pregnancy globally leading to a range of feto-maternal complications. Covid-19 infection has potential to enhance the severity of and complications impending due to anaemia in pregnancy. Objective: To determine the effects of Covid-19 infection on haematological parameters during antenatal care among pregnant women in rural Sindh. Study Design: Cross sectional study. Setting: Shaikh Zaid Institute, Chandka Medical College, Larkana. Duration: From March 1, 2021, and May 31, 2021. Materials and Method: A sample of 110 pregnant women, of 18-50 years of age, presenting in first through third trimester with single alive pregnancy, were included in the study after taking a valid written consent. The Research Evaluation Committee of SMBBMU- Larkana granted approval. Women having any haemoglobinopathy were excluded. Covid-19 test conducted through rt-PCR method. A standard questionnaire was used to collect data of two groups. Analysis was performed through SPSS Version-23. Descriptive and inferential statistics were calculated. Results: Mean ± SD age was 30.3 ± 6.99 (Range: 19 to 45) years. Both groups were identical in age. Mean ± SD gestational age was 28.12 ± 4.66 weeks (Range: 20-38). Covid-19 positive women had lower mean Hb (9.7 ± 2.11) than the covid-19 negative (10.54 ± 2.51;P = 0.158). Other haematological parameters like MCV, serum ferritin, TIBC, TLC & platelets were statistically different between groups. Women of eldest group i-e;in 41-50 years, from urban areas, second trimester (gest. age 13-24 weeks), and nulliparous had been affected more from covid-19 (P = 0.271, 0.748, 0.290 & 0.053). Frequency and severity of anaemia was more among Covid-19 positive women. Conclusion: Covid‐19 demands maternal healthcare to be extra vigilant to the haematological parameters of pregnant women during antenatal care till delivery.

COVID-19 in Children Following Hematopoietic Cell Transplantation: A Multinational Study of the European Bone Marrow Transplantation Society (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH)

Introduction COVID-19 is usually a mild disease in immunocompetent children, with ~1% requiring intensive care unit (ICU) admission and <0.1% mortality. Data on its course in children following hematopoietic cell transplantation (HCT) is limited. Methods Data on children following HCT who developed COVID-19 (diagnosed by positive SARS-CoV-2 PCR on respiratory tract samples) during 3.2020-4.2021 were prospectively collected by EBMT and GETH, including demography, HCT data, COVID-related manifestations, ICU admission and mortality. Factors associated with worse outcomes (ICU admission or mortality) were characterized. Results Sixty-two children (34 boys;median age 9;min-max;0.7-17 years) were reported from 27 centers, 16 countries;57 (92%) following allogeneic and 5 (8%) following autologous HCT. Underlying diseases were acute leukemia (23;37%), inherited disorders (9;15%), hemoglobinopathies (7;11%), solid tumor (6;10%), bone marrow failure (5;8%), other malignant (8;13%) and non-malignant (4;6%) diseases. Five (8%) children had high blood pressure;6 (10%) had underlying lung pathology. The median time from the most recent HCT to COVID was 5 months (min-max;0-169). The stem cell source was bone marrow (33);peripheral (22) or cord blood (1). Among the patients with information available, 34 (62%) underwent in-vivo T cell depletion, 20 (33%) received corticosteroids, and 36 (60%) other immunosuppressant drugs(s) within two months prior to and after the COVID-19 episode. The presence of acute grade 2-4 or chronic graft versus host disease (GVHD) was reported in 12/54 (23%) and 8/51 (16%) children, respectively. Clinical presentation (n=57) included fever (28;49%), cough (18;32%), diarrhea (8;14%), upper respiratory tract disease (as rhinorrhea, sinusitis, otitis, or pharyngitis;12;21%);six (10%) required oxygen to maintain oxygen saturation above 92%;20 children (35%) were asymptomatic. The median time from symptoms onset to COVID diagnosis was 1 day (-43-40). Sixty-three percent of patients were hospitalized;43% due to COVID. The proportion of children with neutropenia or lymphocytopenia (<500 cells/mm 3) was 75% and 73%, respectively. Sixteen children (26%) had evidence of viral (n=10), bacterial (n=6) or fungal (n=2) coinfections. The median time from COVID diagnosis to the last follow-up in alive patients was 69 days (min-max;2 - 294). Six (10%) children who developed COVID at a median 6.5 (min-max;2- 16) months following allo-HCT (median age 6 years;5 boys) required ICU care within a median 6 (min-max;-5-15) days after diagnosis. All of them were neutropenic, received steroids, and other immunosuppressive drugs at COVID diagnosis;5 had undergone in-vivo T cell depletion;5 were lymphocytopenic, 5 had GVHD (2 acute and 3 chronic);3 received non-invasive and 2 invasive ventilation. Three children had viral or bacterial coinfections. Three children died. Six (10%) children (5 boys, median age 10.5 years;min-max;4-13) who developed COVID at median 2 (min-max;0-147) months following allo-HCT died within median 35 days (min-max;5-54) after diagnosis. One had high blood pressure, and none suffered from underlying lung pathology. At the time of COVID, 3 were neutropenic, 2 lymphocytopenic;4 had GVHD (2 acute, 2 chronic);3 received steroids and 4 immunosuppressive drugs. Two had viral or bacterial coinfections. Five had positive SARS-CoV-2 PCR at the time of death. In 3, COVID was the primary cause of death. We compared nine children with the worse outcomes to 53 children with benign course. Among patients alive at 100-day post HCT, the probability of worse outcomes was higher in patients with vs. without chronic GVHD (Figure). No other significant differences were observed in demographic, underlying disease, and HCT-related characteristics. Compared to adults following HCT (Ljungman, Leukemia 2021), children had: - Shorter median time from HCT to COVID diagnosis, 5 vs 18 months;- Higher proportion of asymptomatic infections, 35% vs 9%;- Lower proportion of those who required oxygen, 10% vs 35%;- Lower all-cause mortality, 10% vs 29%. Conclusions Children following HCT with COVID-19 have a higher risk of ICU admission and mortality compared to immune competent children. The presence of chronic GVHD at COVID diagnosis was associated with worse outcomes. COVID course following HCT is milder in children compared to adults. [Formula presented] Disclosures: Averbuch: Takeda: Consultancy;Pfizer: Consultancy;GSK: Speakers Bureau. De La Camara: Roche: Consultancy;IQONE: Consultancy. Corbacioglu: Gentium/Jazz Pharmaceuticals: Consultancy, Honoraria. Mikulska: Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Gilead: Speakers Bureau;MSD: Speakers Bureau;Janssen: Speakers Bureau;Biotest: Speakers Bureau. Kulagin: Roche: Speakers Bureau;Sanofi: Speakers Bureau;Generium: Speakers Bureau;Biocad: Research Funding;Apellis: Research Funding;Alexion: Research Funding;X4 Pharmaceuticals: Research Funding;Novartis: Speakers Bureau;Johnson & Johnson: Speakers Bureau;Pfizer: Speakers Bureau. Cesaro: Sobi: Membership on an entity's Board of Directors or advisory committees;Gilead: Speakers Bureau. Lawson: Alexion: Honoraria. Kroeger: Neovii: Honoraria, Research Funding;Sanofi: Honoraria;Jazz: Honoraria, Research Funding;Celgene: Honoraria, Research Funding;Riemser: Honoraria, Research Funding;Gilead/Kite: Honoraria;AOP Pharma: Honoraria;Novartis: Honoraria. Styczynski: MSD, Pfizer, Giled, TEVA, Jazz, Novartis: Honoraria, Speakers Bureau. Ljungman: Takeda: Consultancy, Other: Endpoint committee, speaker;Enanta: Other: DSMB;Janssen: Other: Investigator;OctaPharma: Other: DSMB;Merck: Other: Investigator, speaker;AiCuris: Consultancy.

Age and genotype dependent erythropoietin protection in COVID-19.

Erythropoietin (EPO) is the main mediator of erythropoiesis and an important tissue protective hormone that appears to mediate an ancestral neuroprotective innate immune response mechanism at an early age. When the young brain is threatened-prematurity, neonatal hyperbilirubinemia, malaria- EPO is hyper-secreted disproportionately to any concurrent anemic stimuli. Under eons of severe malarial selection pressure, neuroprotective EPO augmenting genetic determinants such as the various hemoglobinopathies, and the angiotensin converting enzyme (ACE) I/D polymorphism, have been positively selected. When malarial and other cerebral threats abate and the young child survives to adulthood, EPO subsides. Sustained high ACE and angiotensin II (Ang II) levels through the ACE D allele in adulthood may then become detrimental as witnessed by epidemiological studies. The ubiquitous renin angiotensin system (RAS) influences the α-klotho/fibroblast growth factor 23 (FGF23) circuitry, and both are interconnected with EPO. Here we propose that at a young age, EPO augmenting genetic determinants through ACE D allele elevated Ang II levels in some or HbE/beta thalassemia in others would increase EPO levels and shield against coronavirus disease 2019, akin to protection from malaria and dengue fever. Human evolution may use ACE2 as a "bait" for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to gain cellular entry in order to trigger an ACE/ACE2 imbalance and stimulate EPO hypersecretion using tissue RAS, uncoupled from hemoglobin levels. In subjects without EPO augmenting genetic determinants at any age, ACE2 binding and internalization upon SARS-CoV-2 entry would trigger an ACE/ACE2 imbalance, and Ang II oversecretion leading to protective EPO stimulation. In children, low nasal ACE2 Levels would beneficially augment this imbalance, especially for those without protective genetic determinants. On the other hand, in predisposed adults with the ACE D allele, ACE/ACE2 imbalance, may lead to uncontrolled RAS overactivity and an Ang II induced proinflammatory state and immune dysregulation, with interleukin 6 (IL-6), plasminogen activator inhibitor, and FGF23 elevations. IL-6 induced EPO suppression, aggravated through co-morbidities such as hypertension, diabetes, obesity, and RAS pharmacological interventions may potentially lead to acute respiratory distress syndrome, cytokine storm and/or autoimmunity. HbE/beta thalassemia carriers would enjoy protection at any age as their EPO stimulation is uncoupled from the RAS system. The timely use of rhEPO, EPO analogs, acetylsalicylic acid, bioactive lipids, or FGF23 antagonists in genetically predisposed individuals may counteract those detrimental effects.