Casini, A, Duval, C orcid.org/0000-0002-4870-6542, Pan, X et al. (3 more authors) (2016) Fibrin clot structure in patients with congenital dysfibrinogenaemia. Thrombosis Research, 137. pp. 189-195. ISSN 0049-3848
Abstract
The clinical phenotype of patients with congenital dysfibrinogenaemia is highly heterogeneous, from absence of symptoms to mild bleeding, or thrombosis. A few mutations are associated with a specific phenotype, but generally the clinical course is not predictable. We investigated whether fibrin clot properties are correlated with the patient's phenotype and/or genotype. Ex vivo plasma fibrin clot characteristics, including turbidity, fibrinolysis, clot permeability and fibrin fibre density assessed by laser scanner confocal microscopy were investigated in 24 genotyped patients with congenital dysfibrinogenaemia compared to normal pool plasma. Compared to normal pool plasma, the patients were characterised by slower fibrin polymerisation (lag time, 345.10 ± 22.98 vs. 166.00 s), thinner fibrin fibres (maximum absorbance, 0.15 ± 0.01 vs. 0.31), prolonged clot lysis time (23.72 ± 0.97 vs. 20.32 min) and larger clot pore size (21.5 × 10− 9 ± 4.48 × 10− 9 vs. 7.96 × 10− 9 cm2). Laser scanning confocal microscopy images confirmed disorganised fibrin networks in all patients. Patients with tendency to bleed showed an increased permeability compared to asymptomatic patients (p = 0.01) and to patients with a thrombotic history (p = 0.02) while patients with thrombotic history had a tendency to have a prolonged clot lysis time. Fibrin clot properties were similar among hotspot mutations. Further studies including a larger number of patients are needed to evaluate whether analysis of permeability and clot lysis time may help to distinguish the clinical phenotype in these patients and to assess differences according to the genotype.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | (c) 2016, Elsevier. This is an author produced version of a paper published in Thrombosis Research. Uploaded in accordance with the publisher's self-archiving policy |
Keywords: | Congenital dysfibrinogenaemia; Fibrinolysis; Laser scanner confocal microscopy; Permeability; Mutation |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Academic Unit of Cardiovascular Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Aug 2016 10:50 |
Last Modified: | 03 Nov 2017 05:05 |
Published Version: | http://dx.doi.org/10.1016/j.thromres.2015.11.008 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.thromres.2015.11.008 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:101755 |