Fibrin clot properties to assess the bleeding phenotype in unrelated patients with hypodysfibrinogenemia due to novel fibrinogen mutations.

Clot structure Fibrinogen Frameshift mutation Hypodysfibrinogenemia Laser scanning confocal microscopy Missense mutation Scanning electron microscopy

Journal

Thrombosis research
ISSN: 1879-2472
Titre abrégé: Thromb Res
Pays: United States
ID NLM: 0326377

Informations de publication

Date de publication:
01 2021
Historique:
received: 10 06 2020
revised: 18 09 2020
accepted: 01 11 2020
pubmed: 14 11 2020
medline: 22 6 2021
entrez: 13 11 2020
Statut: ppublish

Résumé

Congenital hypodysfibrinogenemia is a rare fibrinogen disorder, defined by decreased levels of a dysfunctional fibrinogen. We present the functional and structural characterization of two new fibrinogen variants. A duplication of 32 bases in FGA exon 5, p.Ser382GlyfsTer50 was identified in a patient (P1) with history of hemoptysis and traumatic cerebral bleeding. A missense mutation in FGG exon 8, p.Ala353Ser was identified in two siblings (P2 and P3) with tendency to bruising and menorrhagia. Fibrin polymerization was studied in plasma and in purified fibrinogen by turbidimetry. Fibrin structure was studied by a permeability assay, laser scanning confocal microscopy (LSCM) and scanning electron microscopy (SEM). In both plasma and purified fibrinogen samples, all patients had an abnormal polymerization characterized by a decreased maximal absorption compared to controls. The permeation constant (Ks) was markedly increased in all patients: 31 ± 9 × 10

Identifiants

pubmed: 33186848
pii: S0049-3848(20)30598-3
doi: 10.1016/j.thromres.2020.11.003
pii:
doi:

Substances chimiques

Fibrin 9001-31-4
Fibrinogen 9001-32-5

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

56-64

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Auteurs

Rita Marchi (R)

Experimental Medicine, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela; Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Rui Vilar (R)

Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Stéphane Durual (S)

Biomaterials Laboratory, University Clinics of Dental Medicine, University of Geneva.

Matthew Goodyer (M)

Service d'Hématologie, Hôpital du Valais - Institut Central des Hôpitaux, Sion, Switzerland.

Valérie Gay (V)

Hemophilia Treatment Centre, Centre hospitalier Métropole Savoie, Chambery, France.

Marguerite Neerman-Arbez (M)

Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Alessandro Casini (A)

Faculty of Medicine, University of Geneva, Geneva, Switzerland; Division of Angiology and Hemostasis, University Hospitals of Geneva, Geneva, Switzerland. Electronic address: Alessandro.casini@hcuge.ch.

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Classifications MeSH