Obstetrical complications in hereditary fibrinogen disorders: the Fibrinogest study

Hugon-Rodin, Justine; Carrière, Camille; Claeyssens, S.; Trillot, Nathalie; Drillaud, Nicolas; Biron‐Andréani, Christine; Lavenu‐Bombled, Cécile; Wieland, A; Flaujac, Claire; Stieltjes, N.; Lebreton, Aurélien; Brungs, T.; Hegglin, Andrea; Fiore, Mathieu; Desconclois, Céline; Gay, Valérie; Tardy‐Poncet, Brigitte; Beurrier, Philippe; Barbay, Virginie; Chamouni, Pierre; Maistre, Emmanuel de; Šimurda, Tomáš; Casini, Alessandro

doi:10.1016/j.jtha.2023.04.035

Cited by 9 publications

(1 citation statement)

References 24 publications

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“…These findings are comparable with those of a recent study by Hugon-Rodin et al. 42 It is unclear whether replacement therapy can lead to thrombotic events, because some studies have reported that thrombosis is associated with replacement therapies in CFD, but others believe that treatment entails a low risk of thrombosis for CFD patients. 8 , 40 , 43 , 44 , 45 In this study, among 19 patients who received prophylaxis, there was only 1 afibrinogenemic patient (5%) who developed thromboembolism after FC.…”

Section: Discussionsupporting

confidence: 88%

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

Mohsenian,

Palla,

Menegatti

et al. 2024

Blood Advances

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Congenital 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 III 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, 5 hypodysfibrinogenemia) were well characterized. Considering the previously established factor activity and antigen level thresholds, bleeding severity was correctly identified in 58% of cases. The rate of thrombotic events among afibrinogenemic and hypofibrinogenemic patients were relatively similar (11% and 10%) 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. 86 patients received treatment (69 on-demand and/or 17 on prophylaxis), 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 genetics 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.

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Section: Discussionsupporting

confidence: 88%

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

Mohsenian,

Palla,

Menegatti

et al. 2024

Blood Advances

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The β‐Chain Mutation p.Arg17Stop Impairs Fibrinogen Synthesis and Secretion: A Nonsense Mutation Associated With Hypofibrinogenemia

Qian,

Huang,

Luo

et al. 2024

Clinical Laboratory Analysis

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BackgroundCongenital hypofibrinogenemia, a quantitative fibrinogen disorder, is characterized by abnormally low levels of both functional and antigen fibrinogen. We identified a heterozygous nonsense mutation, p.Arg17Stop, in the fibrinogen Bβ chain of a three‐month‐old female infant.MethodsCoagulation testing, gene analysis, in vitro plasmid construction, and functional analyses were conducted to investigate the underlying pathogenic mechanisms.ResultsPlasma fibrinogen levels showed decrease in the proband. DNA sequencing of the proband revealed a heterozygous point mutation (c.139C>T) in exon 2 of the FGB gene causing Arg → Stop substitution. Human Arg17 was found to be highly conserved. In vitro expression analyses indicated that the mutation impacts both the transcription and translation of the FGB gene, subsequently affecting the synthesis and secretion of fibrinogen.ConclusionsThe p.Arg17Stop mutation in the fibrinogen Bβ chain disrupts fibrinogen production and secretion, contributing to hypofibrinogenemia.

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Dysfibrinogenaemia and caesarean delivery: a case report

Dunn,

Coventry,

Lewis

et al. 2024

International Journal of Obstetric Anesthesia

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Obstetrical complications in hereditary fibrinogen disorders: the Fibrinogest study

Cited by 9 publications

References 24 publications

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

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

The β‐Chain Mutation p.Arg17Stop Impairs Fibrinogen Synthesis and Secretion: A Nonsense Mutation Associated With Hypofibrinogenemia

Dysfibrinogenaemia and caesarean delivery: a case report

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