Publications
195 results found
Al-Samkari H, Grace RF, Glenthoj A, et al., 2023, Early-onset reduced bone mineral density in patients with pyruvate kinase deficiency, AMERICAN JOURNAL OF HEMATOLOGY, ISSN: 0361-8609
Grace RF, Glenthoj A, Barcellini W, et al., 2022, Sustained effect on hemoglobin levels and reduced transfusion burden maintained in patients with pyruvate kinase deficiency on mitapivat in a long-term extension study, Publisher: KARGER, Pages: 138-139, ISSN: 2296-5270
Kuo KHM, Layton DM, Lal A, et al., 2022, Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in adults with non-transfusion dependent alpha-thalassaemia or beta-thalassaemia: an open-label, multicentre, phase 2 study, LANCET, Vol: 400, Pages: 493-501, ISSN: 0140-6736
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- Citations: 7
Clayden JD, Stotesbury H, Kawadler JM, et al., 2022, Structural connectivity mediates the relationship between blood oxygenation and cognitive function in sickle cell anemia., Blood Adv
In sickle cell disease (SCD), the relative importance of reduced hemoglobin and peripheral oxygen saturation (SpO2) on brain structure remains uncertain. We applied graph-theoretical analysis to diffusion MRI data to investigate the effect of structural brain connectivity on cognitive function, alongside presence/absence, number and volume of silent cerebral infarction (SCI). In patients, we investigated the relationships between network properties, blood oxygenation and cognition (working memory, WMI, and processing speed, PSI, indices). Based on streamline counts and fractional anisotropy (FA), we identified a subnetwork with weakened connectivity in 92 SCA patients (49 males; 8.0-38.8 years), compared to 54 non-SCA controls (22 males; 6.7-30.6 years). Multiple regression analyses showed a significant effect of hemoglobin on full-network edge density (p<0.05), and of peripheral SpO2 on streamline-weighted subnetwork efficiency (p<0.01). There were effects of FA-weighted full-network and subnetwork efficiency on WMI (both p<0.05), and of streamline-weighted subnetwork efficiency on PSI (p=0.05) but no effects on SCI. Streamline-weighted efficiency was progressively lower with lower SpO2, with a downstream effect on PSI. In path analysis, indirect relationships between blood oxygenation and cognition, mediated by network properties, were better supported than direct alternatives, with an indirect relationship between low SpO2 and PSI in patients, mediated by structural connectivity efficiency in a subnetwork of the brain differing from controls. Our findings are consistent with the notion that cognitive impairment is primarily mediated by hypoxic-ischemic effects on normal-appearing white matter, and highlight the utility of network-based methods in providing biomarkers of cognitive dysfunction in SCA patients.
Joyce KE, Onabanjo E, Brownlow S, et al., 2022, Whole genome sequences discriminate hereditary hemorrhagic telangiectasia phenotypes by non-HHT deleterious DNA variants, Blood Advances, Vol: 6, Pages: 3956-3969, ISSN: 2473-9529
The abnormal vascular structures of hereditary hemorrhagic telangiectasia (HHT) often cause severe anemia due to recurrent hemorrhage, but HHT-causal genes do not predict the severity of hematological complications. We tested for chance inheritance and clinical associations of rare deleterious variants where loss-of-function causes bleeding or hemolytic disorders in the general population. In double-blinded analyses, all 104 HHT patients from a single reference centre recruited to the 100,000 Genomes Project were categorised on new MALO (more/as-expected/less/opposite) sub-phenotype severity scales, and whole genome sequencing data tested for high impact variants in 75 HHT-independent genes encoding coagulation factors, platelet, hemoglobin, erythrocyte enzyme and erythrocyte membrane constituents. Rare variants (all GnomAD allele frequencies <0.003) were identified in 56 (75%) of these 75 HHT-unrelated genes, and in 38/104 (36.5%) of the HHT patients. Likely deleteriousness assignments by Combined Annotation Dependent Depletion (CADD) scores >15 were supported by gene-level mutation significance cutoff (MSC) scores. CADD>15 variants were found for 1 in 10 patients within platelet genes; 1 in 8 within coagulation genes; and 1 in 4 within erythrocyte hemolytic genes. In blinded analyses, patients with greater hemorrhagic severity that had been attributed solely to HHT vessels had more CADD-deleterious variants in platelet (Spearman ρ=0.25, p=0.008) and coagulation (Spearman ρ=0.21, p=0.024) genes. However, the HHT cohort had 60% fewer deleterious variants in platelet and coagulation genes than expected (Mann Whitney p=0.021). In conclusion, HHT patients commonly have rare variants in genes of relevance to their phenotype, offering new therapeutic targets and opportunities for informed, personalised medicine strategies.
Stotesbury H, Kawadler JM, Clayden JD, et al., 2022, Quantification of Silent Cerebral Infarction on High-Resolution FLAIR and Cognition in Sickle Cell Anemia, FRONTIERS IN NEUROLOGY, Vol: 13, ISSN: 1664-2295
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- Citations: 3
Bain BJ, Myburgh J, Hann A, et al., 2022, Voxelotor in sickle cell disease, American Journal of Hematology, Vol: 97, Pages: 830-832, ISSN: 0361-8609
Roy NBA, Da Costa L, Russo R, et al., 2022, The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper, HEMASPHERE, Vol: 6, Pages: 459-477, ISSN: 0007-1048
Roy NBA, Da Costa L, Russo R, et al., 2022, The Use of Next-generation Sequencing in the Diagnosis of Rare Inherited Anaemias: A Joint BSH/EHA Good Practice Paper., Hemasphere, Vol: 6
Stotesbury H, Hales PW, Hood AM, et al., 2022, Individual Watershed Areas in Sickle Cell Anemia: An Arterial Spin Labeling Study, FRONTIERS IN PHYSIOLOGY, Vol: 13
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- Citations: 3
Al-Samkari H, Galacteros F, Glenthoj A, et al., 2022, Mitapivat versus Placebo for Pyruvate Kinase Deficiency, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 386, Pages: 1432-1442, ISSN: 0028-4793
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- Citations: 12
Collington SJ, Nawaz A, Walder S, et al., 2022, Retrospective analysis of the burden of vaso-occlusive events experienced by sickle cell disease (SCD) patients in the integrated health and social care system in North West London, Publisher: WILEY, Pages: 130-131, ISSN: 0007-1048
Dexter D, Layton DM, Kiritkumar K, et al., 2022, Peripheral blood features of iron overload in post-splenectomy, type I congenital dyserythropoietic anemia, American Journal of Hematology, Vol: 97, Pages: 237-238, ISSN: 0361-8609
Stotesbury H, Hales PW, Koelbel M, et al., 2022, Venous cerebral blood flow quantification and cognition in patients with sickle cell anemia, JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, Vol: 42, Pages: 1061-1077, ISSN: 0271-678X
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- Citations: 6
Hui YMT, Gurung K, Layton DM, et al., 2021, Sickle cell disease patients in two London trusts: Genotyping including RH variants, TRANSFUSION MEDICINE, Vol: 32, Pages: 210-220, ISSN: 0958-7578
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- Citations: 1
Grace RF, Glenthoej A, Barcellini W, et al., 2021, Durability of Hemoglobin Response and Reduction in Transfusion Burden Is Maintained over Time in Patients with Pyruvate Kinase Deficiency Treated with Mitapivat in a Long-Term Extension Study, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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- Citations: 1
Kuo KHM, Layton DM, Lal A, et al., 2021, Long-Term Efficacy and Safety of the Oral Pyruvate Kinase Activator Mitapivat in Adults with Non-Transfusion-Dependent Alpha- or Beta-Thalassemia, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
HannyAl-Samkari, Grace RF, Glenthoej A, et al., 2021, Bone Mineral Density Remains Stable in Pyruvate Kinase Deficiency Patients Receiving Long-Term Treatment with Mitapivat, 63rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Bianchi P, Grace RF, Vives Corrons J-L, et al., 2021, Characterizing Iron Overload By Age in Patients Diagnosed with Pyruvate Kinase Deficiency - a Descriptive Analysis from the Peak Registry, Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Al-Samkari H, Grace RF, Glenthoj A, et al., 2021, EARLY-ONSET OSTEOPENIA AND OSTEOPOROSIS IN PATIENTS WITH PYRUVATE KINASE DEFICIENCY, Publisher: FERRATA STORTI FOUNDATION, Pages: 108-108, ISSN: 0390-6078
Cappellini M, Kuo KHM, Layton DM, et al., 2021, ENERGIZE AND ENERGIZE-T: TWO PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDIES OF MITAPIVAT IN ADULTS WITH NON-TRANSFUSION-DEPENDENT OR TRANSFUSION-DEPENDENT ALPHA- OR BETA-THALASSEMIA, Publisher: FERRATA STORTI FOUNDATION, Pages: 110-111, ISSN: 0390-6078
Al-Samkari H, Galacteros F, Glenthoj A, et al., 2021, ACTIVATE: A PHASE 3, RANDOMIZED, MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF MITAPIVAT IN ADULTS WITH PYRUVATE KINASE DEFICIENCY WHO ARE NOT REGULARLY TRANSFUSED, Publisher: FERRATA STORTI FOUNDATION, Pages: 106-106, ISSN: 0390-6078
Bianchi P, van Beers EJ, Vives Corrons J-L, et al., 2021, BASELINE CHARACTERISTICS BY AGE OF A GLOBAL COHORT OF PATIENTS DIAGNOSED WITH PYRUVATE KINASE DEFICIENCY - A DESCRIPTIVE ANALYSIS FROM THE PEAK REGISTRY, Publisher: FERRATA STORTI FOUNDATION, Pages: 107-108, ISSN: 0390-6078
Pal S, Myburgh J, Bansil P, et al., 2021, Reference and point-of-care testing for G6PD deficiency: Blood disorder interference, contrived specimens, and fingerstick equivalence and precision, PLOS ONE, Vol: 16, ISSN: 1932-6203
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- Citations: 3
Al-Samkari H, Galacteros F, Glenthoj A, et al., 2021, ACTIVATE: A phase 3, randomized, multicenter, double-blind, placebo-controlled study of mitapivat in adults with Pyruvate kinase deficiency who are not regularly transfused, Publisher: KARGER, Pages: 40-40, ISSN: 2296-5270
Al-Samkari H, Grace RF, Glenthoj A, et al., 2021, Early-Onset osteopenia and osteoporosis in patients with pyruvate kinase deficiency, Publisher: KARGER, Pages: 170-170, ISSN: 2296-5270
Al-Samkari H, Grace RF, Glenthoej A, et al., 2020, Early-Onset Osteopenia and Osteoporosis in Patients with Pyruvate Kinase Deficiency, 62nd Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
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- Citations: 1
Grace RF, Boscoe A, Bowden C, et al., 2020, Baseline Characteristics of Patients in Peak: A Global, Longitudinal Registry of Patients with Pyruvate Kinase Deficiency, 62nd Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
Layton D, Piel F, Telfer P, 2020, Real-time national survey of COVID-19 in hemoglobinopathy and rare inherited anemia patients, Haematologica: the hematology journal, Vol: 105, Pages: 2651-2654, ISSN: 0390-6078
Roy NBA, Telfer P, Eleftheriou P, et al., 2020, Protecting vulnerable patients with inherited anaemias from unnecessary death during the COVID-19 pandemic, British Journal of Haematology, Vol: 189, Pages: 635-639, ISSN: 0007-1048
With the developing COVID‐19 pandemic, patients with inherited anaemias require specific advice regarding isolation and changes to usual treatment schedules. The National Haemoglobinopathy Panel (NHP) has issued guidance on the care of patients with sickle cell disease, thalassaemia, Diamond Blackfan anaemia (DBA), congenital dyserythropoietic anaemia (CDA), sideroblastic anaemia, pyruvate kinase deficiency and other red cell enzyme and membrane disorders. Cascading of accurate information for clinicians and patients is paramount to preventing adverse outcomes, such as patients who are at increased risk of fulminant bacterial infection due to their condition or its treatment erroneously self‐isolating if their fever is mistakenly attributed to a viral cause, delaying potentially life‐saving antibiotic therapy. Outpatient visits should be minimised for most patients, however some, such as first transcranial dopplers for children with sickle cell anaemia should not be delayed as known risk of stroke will outweigh the unknown risk from COVID‐19 infection. Blood transfusion programmes should be continued, but specific changes to usual clinical pathways can be instituted to reduce risk of patient exposure to COVID‐19, as well as contingency planning for possible reductions in blood available for transfusions. Bone marrow transplants for these disorders should be postponed until further notice. With the current lack of evidence on the risk and complications of COVID‐19 infection in these patients, national data collection is ongoing to record outcomes and eventually to identify predictors of disease severity, particularly important if further waves of infection travel through the population.
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