ArticleBlood2016
A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders.
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Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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82citing papers in PubMed
23.9field-weighted citation impact, top 1% of its field
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Who cites it
82 citing papers in PubMed, 182 citations in OpenAlex.
- Complications of whole-exome sequencing for causal gene discovery in primary platelet secretion defects.Haematologica · 2019Trial
- Application of High-Throughput Sequencing in the Diagnosis of Inherited Thrombocytopenia.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018Trial
- Application of whole-exome sequencing to direct the specific functional testing and diagnosis of rare inherited bleeding disorders in patients from the Öresund Region, Scandinavia.British journal of haematology · 2017Trial
- A sensitized model of thrombosis validates known multigenic relationships and suggests novel modifiers of hemostasis.bioRxiv : the preprint server for biology · 2026Article
- Novel Strategy for Structural Variant Genotyping by Short-Read Genomic Sequencing From Restriction-Circles: Experimental and Bioinformatics Proof-of-Concept.Human mutation · 2026Article
- Molecular diagnosis of inherited platelet disorders: a tale of two realities - advanced vs. resource-limited setting.Thrombosis journal · 2025Review
- How genetic advances are being translated into improved diagnostic outcomes for patients with inherited bleeding disorders.Blood vessels, thrombosis & hemostasis · 2025Review
- Integrating Next-Generation Sequencing Into Routine Molecular Diagnosis of Inherited Coagulation Factor Deficiencies: Real-World Data From Spanish Patients.Haemophilia : the official journal of the World Federation of Hemophilia · 2025Article
- Application of multigene panel testing for bleeding, thrombotic, and platelet disorders in patients and the general population in China.Molecular biomedicine · 2025Article
- The role of genetic sequencing in the diagnostic workup for chronic immune thrombocytopenia.Blood advances · 2025Article
- Screening for gene variants causing inherited platelet disorders: are the cons always cons?Blood vessels, thrombosis & hemostasis · 2025Article
- Targeted exome analysis in patients with rare bleeding disorders: data from the Rare Bleeding Disorders in the Netherlands study.Research and practice in thrombosis and haemostasis · 2024Article
- Article
- High-throughput microfluidic blood testing to phenotype genetically linked platelet disorders: an aid to diagnosis.Blood advances · 2023Article
- An Exploratory Study Using Next-Generation Sequencing to Identify Prothrombotic Variants in Patients with Cerebral Vein Thrombosis.International journal of molecular sciences · 2023Article
- A family case series of inherited thrombocytopenia.Proceedings (Baylor University. Medical Center) · 2023Article
- The association between EPCR gene p.Ser219Gly polymorphism and venous thromboembolism risk: a case-control study, meta-analysis, and a reproducibility study.Frontiers in cardiovascular medicine · 2023Review
- [Research progress of Molecular diagnostic technique in Venous Thromboembolism].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2022Article
- Precision medicine in trauma: a transformational frontier in patient care, education, and research.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2022Review
- Detection of Unknown and Rare Pathogenic Variants in Antithrombin, Protein C and Protein S Deficiency Using High-Throughput Targeted Sequencing.Diagnostics (Basel, Switzerland) · 2022Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
79 authors at 20 institutions in 12 countries.
Ilenia SimeoniDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and.
Jonathan C StephensDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom;
Fengyuan HuDepartment of Haematology, University of Cambridge, Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom;
Sri V V DeeviDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and.
Karyn MegyDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and.
Tadbir K BarianaThe Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free London National Health Service Foundation Trust, London, United Kingdom; Department of Haematology, University College London Cancer Institute, London, United Kingdom;
Claire LentaigneCentre for Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, and Imperial College Healthcare National Health Service Trust, London, United Kingdom;
Sol SchulmanDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA;
Suthesh SivapalaratnamDepartment of Haematology, University of Cambridge, National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom; Department of Haematology, Barts Health National Health Service Trust, London, United Kingdom;
Minka J A VriesDepartment of Biochemistry, Maastricht University, Maastricht, The Netherlands;
Sarah K WestburySchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom;
Daniel GreeneDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Cambridge Biomedical Campus, Cambridge, United Kingdom;
Sofia PapadiaDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and.
Marie-Christine AlessiInstitut National de la Santé et de la Recherche Médicale, Faculté de Médecine, Marseille, France;
Antony P AttwoodDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom;
Matthias BallmaierPediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany;
Gareth BaynamSchool of Paediatrics and Child Health, The University of Western Australia, Crawley, Australia; Western Australia Register of Developmental Anomalies, King Edward Memorial Hospital, Subiaco, Australia; Office of Population Health Genomics, WA Department of Health, East Perth, Australia; Institute of Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia; Telethon Kids Institute, Subiaco, Australia;
Emilse BermejoHematological Research Institute, National Academy of Medicine, Buenos Aires, Argentina;
Marta BertoliSan Pietro Fatebenefratelli Hospital, Unita' Operativa Semplice Dipartimentale, Medical Genetics, Rome, Italy;
Paul F BrayDepartment of Medicine, Thomas Jefferson University, Jefferson Medical College, Philadelphia, PA;
Loredana BuryDepartment of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy;
Marco CattaneoDipartimento di Scienze Della Salute, Università Degli Studi di Milano, Unità di Medicina, Azienda Ospedaliera San Paolo, Milan, Italy;
Peter CollinsArthur Bloom Haemophilia Centre, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom;
Louise C DaughertyDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and.
Rémi FavierAssistance Publique, Hôpitaux de Paris, Armand Trousseau Children Hospital, Paris, Inserm U1170, Villejuif, France;
Deborah L FrenchDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA;
Bruce FurieDivision of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA;
Michael GattensDepartment of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom;
Manuela GermeshausenPediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany;
Cedric GhevaertDepartment of Haematology, University of Cambridge, National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom;
Anne C GoodeveHaemostasis Research Group, Department of Infection, Immunity and Cardiovascular Disease, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, United Kingdom;
Jose A GuerreroDepartment of Haematology, University of Cambridge.
Daniel J HampshireHaemostasis Research Group, Department of Infection, Immunity and Cardiovascular Disease, Faculty of Medicine, Dentistry and Health, University of Sheffield, Sheffield, United Kingdom;
Daniel P HartDepartment of Haematology, Barts Health National Health Service Trust, London, United Kingdom;
Johan W M HeemskerkDepartment of Biochemistry, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands;
Yvonne M C HenskensDepartment of Biochemistry, Maastricht University, Maastricht, The Netherlands;
Marian HillDepartment of Clinical Pathology, Empath Pathology Services, Nottingham University Hospitals National Health Service Trust, Nottingham, United Kingdom;
Nancy HoggCancer Research UK London Research Institute, London, United Kingdom;
Jennifer D JolleyComponents Development Laboratory, National Health Service Blood and Transplant, Cambridge, United Kingdom;
Walter H KahrDepartment of Paediatrics, Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada;
Anne M KellyDepartment of Haematology, Great Ormond Street Hospital for Children National Health Service Trust, London, United Kingdom;
Ron KerrDepartment of Haematology, Ninewells Hospital, Dundee, United Kingdom;
Myrto KostadimaDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and.
Shinji KunishimaClinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan;
Michele P LambertDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;
Ri LiesnerDepartment of Haematology, Ninewells Hospital, Dundee, United Kingdom;
José A LópezPuget Sound Blood Center, Research Institute, Seattle, WA;
Rutendo P MapetaDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and.
Mary MathiasDepartment of Haematology, Ninewells Hospital, Dundee, United Kingdom;
Carolyn M MillarCentre for Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, and Imperial College Healthcare National Health Service Trust, London, United Kingdom;
Amit NathwaniDepartment of Haematology, University College London Cancer Institute, London, United Kingdom;
Marguerite Neerman-ArbezDepartment of Genetic Medicine and Development, University Medical Centre, Geneva, Switzerland;
Alan T NurdenInstitut Hospitalo-Universitaire LIRYC, Hôpital Xavier Arnozan, Pessac, France;
Paquita NurdenInstitut Hospitalo-Universitaire LIRYC, Hôpital Xavier Arnozan, Pessac, France;
Maha OthmanDepartment of Biomedical and Molecular Sciences, School of Medicine, Queens University, Kingston, Ontario, Canada;
Kathelijne PeerlinckDepartment of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium;
David J PerryDepartment of Haematology, Addenbrooke's Hospital, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom;
Pawan PoudelInstitute of Cancer Research, London, United Kingdom;
Pieter ReitsmaEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands;
Matthew T RondinaUniversity of Utah School of Medicine, Eccles Institute of Human Genetics, Salt Lake City, UT;
Peter A SmethurstDepartment of Haematology, University of Cambridge, Department of Paediatrics, Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada;
William StevensonDepartment of Haematology and Transfusion Medicine, Royal North Shore Hospital, St. Leonards, NSW, Australia; Kolling Institute of Medical Research, The University of Sydney, Sydney, Australia;
Artur SzkotakLaboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada;
Salih TunaDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and.
Christel van GeetInstitute of Cancer Research, London, United Kingdom;
Deborah WhitehornDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and.
David A WilcoxChildren's Hospital of Wisconsin Research Institute, Medical College of Wisconsin, Milwaukee, WI;
Bin ZhangGenomic Medicine Institute, Cleveland Clinic Lerner Research Institute, Cleveland, OH;
Shoshana Revel-VilkPediatric Hematology/Oncology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel;
Paolo GreseleDepartment of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy;
Daniel B BellissimoClinical Genomics Laboratory, University of Pittsburgh, Pittsburgh, PA;
Christopher J PenkettDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and.
Michael A LaffanCentre for Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College London, and Imperial College Healthcare National Health Service Trust, London, United Kingdom;
Andrew D MumfordSchool of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom; School of Clinical Sciences, University of Bristol, Bristol, United Kingdom;
Augusto RendonDepartment of Haematology, University of Cambridge, Genomics England Limited, London, United Kingdom; and.
Keith GomezThe Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free London National Health Service Foundation Trust, London, United Kingdom; Department of Haematology, University College London Cancer Institute, London, United Kingdom;
Kathleen FresonInstitute of Cancer Research, London, United Kingdom;
Willem H OuwehandDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
Ernest TurroDepartment of Haematology, University of Cambridge, National Institute for Health Research BioResource-Rare Diseases, Cambridge University Hospitals, and National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge, United Kingdom; Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Cambridge Biomedical Campus, Cambridge, United Kingdom;
National Health Service · GBUniversity of Cambridge · GBInstitute of Cancer Research · GBMaastricht University · NLNinewells Hospital · GBBeth Israel Deaconess Medical Center · USChildren's Hospital of Philadelphia · USElectrophysiology and Heart Modeling Institute · FRInserm · FRMedizinische Hochschule Hannover · DEUniversity of Bristol · GBUniversity of Perugia · ITUniversity of Sheffield · GBUniversity of Toronto · CAAcademia Nacional de Medicina · ARBabraham Institute · GBBloodworks Northwest · USCancer Research UK · GBCardiff University · GBChildren's Hospital of Wisconsin · US
Funding
Zimmerman Program for the Molecular and Clinical Biology of VWDP01HL081588 · NHLBI · VERSITI WISCONSIN, INC. · PI MONTGOMERY, ROBERT R · 2005 to 2016
$19.3MER-to-Golgi transport of coagulation factors V and VIIIR01HL094505 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI ZHANG, BIN · 2009 to 2022
$5.1MVariation in platelet function: the genetics of platelet gene expressionR01HL102482 · NHLBI · UNIVERSITY OF UTAH · PI BRAY, PAUL F. · 2010 to 2018
$4.6MBritish Heart Foundation FS/09/039/27788British Heart Foundation RG/09/012/28096Department of Health RP-PG-0310-1002Medical Research Council MC_PC_12009Medical Research Council MR/J011711/1Medical Research Council MR/K023489/1Medical Research Council MR/L022982/1NHLBI NIH HHS P01 HL081588NHLBI NIH HHS R01 HL094505NHLBI NIH HHS R01 HL102482Wellcome Trust
Abstract
Inherited bleeding, thrombotic, and platelet disorders (BPDs) are diseases that affect ∼300 individuals per million births. With the exception of hemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialized tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached, which can compromise treatment and impede rapid identification of affected relatives. To address this unmet diagnostic need, we designed a high-throughput sequencing platform targeting 63 genes relevant for BPDs. The platform can call single nucleotide variants, short insertions/deletions, and large copy number variants (though not inversions) which are subjected to automated filtering for diagnostic prioritization, resulting in an average of 5.34 candidate variants per individual. We sequenced 159 and 137 samples, respectively, from cases with and without previously known causal variants. Among the latter group, 61 cases had clinical and laboratory phenotypes indicative of a particular molecular etiology, whereas the remainder had an a priori highly uncertain etiology. All previously detected variants were recapitulated and, when the etiology was suspected but unknown or uncertain, a molecular diagnosis was reached in 56 of 61 and only 8 of 76 cases, respectively. The latter category highlights the need for further research into novel causes of BPDs. The ThromboGenomics platform thus provides an affordable DNA-based test to diagnose patients suspected of having a known inherited BPD.
Indexed as
Genetic Predisposition to DiseaseBlood Platelet DisordersCase-Control StudiesDNA Copy Number VariationsFemaleGenetic Association StudiesHemorrhageHigh-Throughput Nucleotide SequencingHumansMaleMutationPolymorphism, Single NucleotideSequence Analysis, DNAThrombosis
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