Congenital afibrinogenemia: from etiopathogenesis to challenging clinical management

Stančiaková, Lucia; Kubisz, Peter; Dobrotová, Miroslava; Staško, Ján

doi:10.1080/17474086.2016.1200967

Cited by 18 publications

(23 citation statements)

References 81 publications

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“…In hypofibrinogenemia, standard clotting assays are variably prolonged according to the circulating fibrinogen level. Functional and antigenic fibrinogen levels are proportionally decreased [ 7 ]. A ratio of functional on antigenic fibrinogen level higher than 0.7 is traditionally used to distinguish between hypofibrinogenemia and dysfibrinogenemia [ 8 ], although the sensitivity and specificity of this cut-off has never been established [ 9 ].…”

Section: Diagnosis Of Quantitative Fibrinogen Disordersmentioning

confidence: 99%

Clinical Consequences and Molecular Bases of Low Fibrinogen Levels

Neerman-Arbez

Casini

2018

IJMS

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Abstract:The study of inherited fibrinogen disorders, characterized by extensive allelic heterogeneity, allows the association of defined mutations with specific defects providing significant insight into the location of functionally important sites in fibrinogen and fibrin. Since the identification of the first causative mutation for congenital afibrinogenemia, studies have elucidated the underlying molecular pathophysiology of numerous causative mutations leading to fibrinogen deficiency, developed cell-based and animal models to study human fibrinogen disorders, and further explored the clinical consequences of absent, low, or dysfunctional fibrinogen. Since qualitative disorders are addressed by another review in this special issue, this review will focus on quantitative disorders and will discuss their diagnosis, clinical features, molecular bases, and introduce new models to study the phenotypic consequences of fibrinogen deficiency.

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Section: Diagnosis Of Quantitative Fibrinogen Disordersmentioning

confidence: 99%

Clinical Consequences and Molecular Bases of Low Fibrinogen Levels

Neerman-Arbez

Casini

2018

IJMS

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“…It is synthesized in the liver and circulates in plasma at concentrations of 2-4 g/L. (8)(9)(10) Hypofibrinogenemia is a rare hematologic disorder that has no established incidence due to the absence of symptoms in most affected patients; it has a recessive inheritance pattern as does afibrinogenemia. In patients with hemorrhages of unknown etiology, studies should look for coagulation disorders.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous vulvar hematoma as a rare manifestation of congenital hypofibrinogenemia. Case report

et al. 2019

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Introduction: Congenital fibrinogen disorders are rare conditions in which there are quantitative and qualitative alterations of factor I; the vast majority of patients are asymptomatic.Case presentation: A 19-year-old female patient with a history of congenital hypofibrinogenemia presented with spontaneous vulvar hematoma along with hypotension, tachycardia, stupor and hematoma of 20cm in the right labium majus. On admission, the young woman had hemoglobin 6.6 g/dL, fibrinogen 74 mg/dL and prolonged clotting times. She received red blood cells transfusion and cryoprecipitates, followed by surgical drainage and intravenous fibrinogen replacement, adjusting the dose according to fibrinogen levels in plasma. The patient presented progressive improvement without hemorrhagic recurrence and fibrinogen levels within the target values until hospital discharge.Discussion: Afibrinogenemia and hypofibrinogenemia are part of the quantitative factor I disorders; in the first case, there is total absence of circulating fibrinogen, and in the second case the levels are below 150 mg/dL. Spontaneous vulvar hematoma as a severe hemorrhagic manifestation is not frequent in symptomatic patients; its treatment is based on fibrinogen replacement in an individualized manner and surgical management when required.Conclusion: Hypofibrinogenemia is a rare disease, and fibrinogen replacement is one of the mainstays of treatment.

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“…Musculoskeletal bleeding (and also bleeding into the joints) is reported in approximately half of the individuals with afibrinogenemia, and, in some studies, it was more prevalent than bleedings from mucosal surfaces. Bleeding from the gastrointestinal and urinary system occurs less frequently [ 36 , 37 ]. Moreover, quantitative fibrinogen abnormalities can lead to complicated wound healing [ 10 , 21 ].…”

Section: Congenital Fibrinogen Disordersmentioning

confidence: 99%

Genetic Variants in the FGB and FGG Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype

Šimurda

Brunclíková

Asselta

et al. 2020

IJMS

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Fibrinogen is a hexameric plasmatic glycoprotein composed of pairs of three chains (Aα, Bβ, and γ), which play an essential role in hemostasis. Conversion of fibrinogen to insoluble polymer fibrin gives structural stability, strength, and adhesive surfaces for growing blood clots. Equally important, the exposure of its non-substrate thrombin-binding sites after fibrin clot formation promotes antithrombotic properties. Fibrinogen and fibrin have a major role in multiple biological processes in addition to hemostasis and thrombosis, i.e., fibrinolysis (during which the fibrin clot is broken down), matrix physiology (by interacting with factor XIII, plasminogen, vitronectin, and fibronectin), wound healing, inflammation, infection, cell interaction, angiogenesis, tumour growth, and metastasis. Congenital fibrinogen deficiencies are rare bleeding disorders, characterized by extensive genetic heterogeneity in all the three genes: FGA, FGB, and FGG (enconding the Aα, Bβ, and γ chain, respectively). Depending on the type and site of mutations, congenital defects of fibrinogen can result in variable clinical manifestations, which range from asymptomatic conditions to the life-threatening bleeds or even thromboembolic events. In this manuscript, we will briefly review the main pathogenic mechanisms and risk factors leading to thrombosis, and we will specifically focus on molecular mechanisms associated with mutations in the C-terminal end of the beta and gamma chains, which are often responsible for cases of congenital afibrinogenemia and hypofibrinogenemia associated with thrombotic manifestations.

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Congenital afibrinogenemia: from etiopathogenesis to challenging clinical management

Cited by 18 publications

References 81 publications

Clinical Consequences and Molecular Bases of Low Fibrinogen Levels

Clinical Consequences and Molecular Bases of Low Fibrinogen Levels

Spontaneous vulvar hematoma as a rare manifestation of congenital hypofibrinogenemia. Case report

Genetic Variants in the FGB and FGG Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype

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