Congenital fibrinogen disorders: a retrospective clinical and genetic analysis of the Prospective Rare Bleeding Disorders Database

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dc.contributor.authorMohsenian, S.
dc.contributor.authorPalla, R.
dc.contributor.authorMenegatti, M.
dc.contributor.authorCairo, A.
dc.contributor.authorLecchi, A.
dc.contributor.authorCasini, A.
dc.contributor.authorNeerman-Arbez M.
dc.date.accessioned2024-05-19T14:34:45Z
dc.date.available2024-05-19T14:34:45Z
dc.date.issued2024
dc.departmentİstinye Üniversitesien_US
dc.description.abstractCongenital fibrinogen deficiency (CFD) is a rare bleeding disorder caused by mutations in FGA, FGB, and FGG. We sought to comprehensively characterize patients with CFD using PRO-RBDD (Prospective Rare Bleeding Disorders Database). Clinical phenotypes, laboratory, and genetic features were investigated using retrospective data from the PRO-RBDD. Patients were classified from asymptomatic to grade 3 based on their bleeding severity. In addition, FGA, FGB, and FGG were sequenced to find causative variants. A total of 166 CFD cases from 16 countries were included, of whom 123 (30 afibrinogenemia, 33 hypofibrinogenemia, 55 dysfibrinogenemia, and 5 hypodysfibrinogenemia) were well characterized. Considering the previously established factor activity and antigen level thresholds, bleeding severity was correctly identified in 58% of the cases. The rates of thrombotic events among afibrinogenemic and hypofibrinogenemic patients were relatively similar (11% and 10%, respectively) and surprisingly higher than in dysfibrinogenemic cases. The rate of spontaneous abortions among 68 pregnancies was 31%, including 86% in dysfibrinogenemic women and 14% with hypofibrinogenemia. Eighty-six patients received treatment (69 on-demand and/or 17 on prophylaxis), with fibrinogen concentrates being the most frequently used product. Genetic analysis was available for 91 cases and 41 distinct variants were identified. Hotspot variants (FGG, p.Arg301Cys/His and FGA, p.Arg35Cys/His) were present in 51% of dysfibrinogenemia. Obstetric complications were commonly observed in dysfibrinogenemia. This large multicenter study provided a comprehensive insight into the clinical, laboratory, and genetic history of patients with CFDs. We conclude that bleeding severity grades were in agreement with the established factor activity threshold in nearly half of the cases with quantitative defects. © 2024 by The American Society of Hematology.en_US
dc.description.sponsorshipEuropean Association for Haemophilia and Allied Disorders, EAHAD; European Commission, ECen_US
dc.description.sponsorshipConsidering this background, we performed a cross-sectional study within the Prospective Rare Bleeding Disorders Database (PRO-RBDD) with the goal of describing the laboratory, clinical and genetic features of a well-defined group of patients with CFD. In addition, we aimed to assess the association between factor activity level and clinical severity in a more comprehensive way to confirm the EN-RBD results in a wider and different cohort of patients.18 Another aim was to find the difference between the age of diagnosis among different types of fibrinogen deficiency. This study was designed within the European Haemophilia Network activities with the support of the European Association for Haemophilia and Allied Disorders and the European Commissionen_US
dc.identifier.doi10.1182/bloodadvances.2023012186
dc.identifier.endpage1404en_US
dc.identifier.issn2473-9529
dc.identifier.issue6en_US
dc.identifier.pmid38286442en_US
dc.identifier.scopus2-s2.0-85188776419en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1392en_US
dc.identifier.urihttps://doi.org/10.1182/bloodadvances.2023012186
dc.identifier.urihttps://hdl.handle.net/20.500.12713/4547
dc.identifier.volume8en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmerican Society of Hematologyen_US
dc.relation.ispartofBlood Advancesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmz20240519_kaen_US
dc.subjectAnticoagulant Agenten_US
dc.subjectD Dimeren_US
dc.subjectFibrinogenen_US
dc.subjectFibrinogen Concentrateen_US
dc.subjectVitamin K Groupen_US
dc.subjectActivated Partial Thromboplastin Timeen_US
dc.subjectAdulten_US
dc.subjectAfibrinogenemiaen_US
dc.subjectArticleen_US
dc.subjectBleeding Disorderen_US
dc.subjectData Baseen_US
dc.subjectDysfibrinogenemiaen_US
dc.subjectFemaleen_US
dc.subjectFibrinogen Defecten_US
dc.subjectGene Mutationen_US
dc.subjectGenetic Analysisen_US
dc.subjectGenetic Counselingen_US
dc.subjectGenotypeen_US
dc.subjectGenotypingen_US
dc.subjectHaplotypeen_US
dc.subjectHematomaen_US
dc.subjectHeredityen_US
dc.subjectHeterozygoteen_US
dc.subjectHumanen_US
dc.subjectHypofibrinogenemiaen_US
dc.subjectMajor Clinical Studyen_US
dc.subjectMaleen_US
dc.subjectMissense Mutationen_US
dc.subjectMolecular Dynamicsen_US
dc.subjectMyelooptic Neuropathyen_US
dc.subjectPhenotypeen_US
dc.subjectPolymerase Chain Reactionen_US
dc.subjectPostpartum Hemorrhageen_US
dc.subjectPredictive Valueen_US
dc.subjectPrenatal Diagnosisen_US
dc.subjectProspective Rare Bleeding Disorders Databaseen_US
dc.subjectProspective Studyen_US
dc.subjectRankin Scaleen_US
dc.subjectRetrospective Studyen_US
dc.subjectRna Splicingen_US
dc.subjectSanger Sequencingen_US
dc.subjectSensitivity And Specificityen_US
dc.subjectSpontaneous Abortionen_US
dc.subjectThrombocytopeniaen_US
dc.subjectWhole Exome Sequencingen_US
dc.titleCongenital fibrinogen disorders: a retrospective clinical and genetic analysis of the Prospective Rare Bleeding Disorders Databaseen_US
dc.typeArticleen_US

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