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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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/4/1083 |
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| author | Monika Brunclikova Tomas Simurda Jana Zolkova Miroslava Sterankova Ingrid Skornova Miroslava Dobrotova Zuzana Kolkova Dusan Loderer Marian Grendar Jan Hudecek Jan Stasko Peter Kubisz |
| author_facet | Monika Brunclikova Tomas Simurda Jana Zolkova Miroslava Sterankova Ingrid Skornova Miroslava Dobrotova Zuzana Kolkova Dusan Loderer Marian Grendar Jan Hudecek Jan Stasko Peter Kubisz |
| author_sort | Monika Brunclikova |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T21:41:17Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T21:41:17Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-bed0d4d8ea834cc18101bf03adc25b192023-11-23T20:31:23ZengMDPI AGJournal of Clinical Medicine2077-03832022-02-01114108310.3390/jcm11041083Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and ThrombosisMonika Brunclikova0Tomas Simurda1Jana Zolkova2Miroslava Sterankova3Ingrid Skornova4Miroslava Dobrotova5Zuzana Kolkova6Dusan Loderer7Marian Grendar8Jan Hudecek9Jan Stasko10Peter Kubisz11National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaNational Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaNational Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaNational Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaNational Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaNational Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaBiomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaBiomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaBiomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaNational Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaNational Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaNational Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, University Hospital in Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, SlovakiaCongenital 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.https://www.mdpi.com/2077-0383/11/4/1083fibrinogenhypofibrinogenemiaheterogeneity of phenotypemutations associated with bleeding and thrombosis |
| spellingShingle | Monika Brunclikova Tomas Simurda Jana Zolkova Miroslava Sterankova Ingrid Skornova Miroslava Dobrotova Zuzana Kolkova Dusan Loderer Marian Grendar Jan Hudecek Jan Stasko Peter Kubisz Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis Journal of Clinical Medicine fibrinogen hypofibrinogenemia heterogeneity of phenotype mutations 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 | fibrinogen hypofibrinogenemia heterogeneity of phenotype mutations associated with bleeding and thrombosis |
| url | https://www.mdpi.com/2077-0383/11/4/1083 |
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