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Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis

Congenital fibrinogen disorders are diseases associated with a bleeding tendency; however, there are also reports of thrombotic events. Fibrinogen plays a role in the pathogenesis of thrombosis due to altered plasma concentrations or modifications to fibrinogen’s structural properties, which affect...

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Autores principales: Brunclikova, Monika, Simurda, Tomas, Zolkova, Jana, Sterankova, Miroslava, Skornova, Ingrid, Dobrotova, Miroslava, Kolkova, Zuzana, Loderer, Dusan, Grendar, Marian, Hudecek, Jan, Stasko, Jan, Kubisz, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874973/
https://www.ncbi.nlm.nih.gov/pubmed/35207353
http://dx.doi.org/10.3390/jcm11041083
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author Brunclikova, Monika
Simurda, Tomas
Zolkova, Jana
Sterankova, Miroslava
Skornova, Ingrid
Dobrotova, Miroslava
Kolkova, Zuzana
Loderer, Dusan
Grendar, Marian
Hudecek, Jan
Stasko, Jan
Kubisz, Peter
author_facet Brunclikova, Monika
Simurda, Tomas
Zolkova, Jana
Sterankova, Miroslava
Skornova, Ingrid
Dobrotova, Miroslava
Kolkova, Zuzana
Loderer, Dusan
Grendar, Marian
Hudecek, Jan
Stasko, Jan
Kubisz, Peter
author_sort Brunclikova, Monika
collection PubMed
description Congenital fibrinogen disorders are diseases associated with a bleeding tendency; however, there are also reports of thrombotic events. Fibrinogen plays a role in the pathogenesis of thrombosis due to altered plasma concentrations or modifications to fibrinogen’s structural properties, which affect clot permeability, resistance to lysis, and its stiffness. Several distinct types of genetic change and pathogenetic mechanism have been described in patients with bleeding and a thrombotic phenotype, including mutations affecting synthesis or processing in three fibrinogen genes. In this paper, we focused on familial hypofibrinogenemia, a rare inherited quantitative fibrinogen disorder characterized by decreased fibrinogen levels with a high phenotypic heterogeneity. To begin, we briefly review the basic information regarding fibrinogen’s structure, its function, and the clinical consequences of low fibrinogen levels. Thereafter, we introduce 15 case reports with various gene mutations derived from the fibrinogen mutation database GFHT (French Study Group on Hemostasis and Thrombosis), which are associated with congenital hypofibrinogenemia with both bleeding and thrombosis. Predicting clinical presentations based on genotype data is difficult. Genotype–phenotype correlations would be of help to better understand the pathologic properties of this rare disease and to provide a valuable tool for the identification of patients who are not only at risk of bleeding, but also at risk of a thrombotic event.
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spelling pubmed-88749732022-02-26 Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis Brunclikova, Monika Simurda, Tomas Zolkova, Jana Sterankova, Miroslava Skornova, Ingrid Dobrotova, Miroslava Kolkova, Zuzana Loderer, Dusan Grendar, Marian Hudecek, Jan Stasko, Jan Kubisz, Peter J Clin Med Review Congenital fibrinogen disorders are diseases associated with a bleeding tendency; however, there are also reports of thrombotic events. Fibrinogen plays a role in the pathogenesis of thrombosis due to altered plasma concentrations or modifications to fibrinogen’s structural properties, which affect clot permeability, resistance to lysis, and its stiffness. Several distinct types of genetic change and pathogenetic mechanism have been described in patients with bleeding and a thrombotic phenotype, including mutations affecting synthesis or processing in three fibrinogen genes. In this paper, we focused on familial hypofibrinogenemia, a rare inherited quantitative fibrinogen disorder characterized by decreased fibrinogen levels with a high phenotypic heterogeneity. To begin, we briefly review the basic information regarding fibrinogen’s structure, its function, and the clinical consequences of low fibrinogen levels. Thereafter, we introduce 15 case reports with various gene mutations derived from the fibrinogen mutation database GFHT (French Study Group on Hemostasis and Thrombosis), which are associated with congenital hypofibrinogenemia with both bleeding and thrombosis. Predicting clinical presentations based on genotype data is difficult. Genotype–phenotype correlations would be of help to better understand the pathologic properties of this rare disease and to provide a valuable tool for the identification of patients who are not only at risk of bleeding, but also at risk of a thrombotic event. MDPI 2022-02-18 /pmc/articles/PMC8874973/ /pubmed/35207353 http://dx.doi.org/10.3390/jcm11041083 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Brunclikova, Monika
Simurda, Tomas
Zolkova, Jana
Sterankova, Miroslava
Skornova, Ingrid
Dobrotova, Miroslava
Kolkova, Zuzana
Loderer, Dusan
Grendar, Marian
Hudecek, Jan
Stasko, Jan
Kubisz, Peter
Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis
title Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis
title_full Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis
title_fullStr Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis
title_full_unstemmed Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis
title_short Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis
title_sort heterogeneity of genotype–phenotype in congenital hypofibrinogenemia—a review of case reports associated with bleeding and thrombosis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874973/
https://www.ncbi.nlm.nih.gov/pubmed/35207353
http://dx.doi.org/10.3390/jcm11041083
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