Perioperative management of a severe congenital hypofibrinogenemia with thrombotic phenotype

Šimurda, Tomáš; Casini, Alessandro; Staško, Ján; Hudeček, Jan; Škorňová, Ingrid; Vilar, R.; Neerman-Arbez, Marguerite; Kubisz, Peter

doi:10.1016/j.thromres.2020.01.024

Cited by 26 publications

(29 citation statements)

References 16 publications

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“…The switch of an uncharged aromatic amino-acid side chain with a positively charged residue is likely to interfere with the correct binding of the βC domain by modifying the delicate balance in the distribution of hydrophobic and hydrophilic regions. This change can result in the incorrect composition of the βC domain and reduction of fibrinogen hexamer secretion compatible with the observed hypofibrinogenemia [26,33].…”

Section: Fibrinogen Martin IImentioning

confidence: 85%

“…Due to the low prevalence of hypofibrinogenemia and afibrinogenemia, there is little information on pathophysiology or optimal treatment of thrombosis in these patients. Managing patients with CFD with thrombotic events is challenging as anticoagulant treatment may exacerbate the underlying bleeding risk, which can be life-threatening [33]. We hope that this article will generate additional interest in investigators who may eventually contribute to the better understanding of the development of thromboembolic complications in patients with a low level of fibrinogen.…”

Section: Discussionmentioning

confidence: 99%

“…Congenital hypofibrinogenemia is generally more frequent than afibrinogenemia, but prevalence is difficult to establish due to the large number of asymptomatic patients. In Slovakia, the prevalence of congenital hypofibrinogenemia was estimated to be 1 in 50,000 [33].…”

Section: Classificationmentioning

confidence: 99%

“…In afibrinogenemia and hypofibrinogenemia, there is a concomitant decrease in fibrinogen antigen tested by immunoassay, gravimetric assays, or by measurement of dry clot weight [61]. Rotational thromboelastography was also proposed as a universal method for monitoring the reaction to administered fibrinogen in subjects with fibrinogen deficiency [33,62]. Maximum clot firmness (one of its parameters) can confirm the effectiveness and safety of normalization of clot formation after the infusion of fibrinogen [33,63,64].…”

Section: Laboratory Analysesmentioning

confidence: 99%

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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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Section: Fibrinogen Martin IImentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Classificationmentioning

confidence: 99%

Section: Laboratory Analysesmentioning

confidence: 99%

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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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“…52 Point-of-care viscoelastic tests such as the rotational thromboelastometry or the thromboelastography are used as surrogate endpoints in randomized trials on fibrinogen concentrates 53 or to guide the hemostatic management in high bleeding risk surgeries. 54 However, they could have a limited sensitivity to certain changes in fibrin network structure and function, reducing their utility to a small number of patients. 55 Further studies are needed to define whether these tests could be used to monitor the fibrinogen replacement 56 or whether they could be of diagnosis or prognostic value.…”

Section: Research On Congenital Fibrinogen Disordersmentioning

confidence: 99%

From Routine to Research Laboratory: Strategies for the Diagnosis of Congenital Fibrinogen Disorders

Casini

2020

Hamostaseologie

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AbstractCongenital fibrinogen disorders (CFDs) encompass a heterogeneous group of fibrinogen defects with a wide spectrum of biological and clinical features. An accurate diagnosis is thus essential to assure the optimal management for the patient. Diagnosis involves a multistep approach starting with routine coagulation assays and assessment of functional and antigenic fibrinogen followed by identification of the molecular anomaly. However, the diagnosis of CFD can be challenging as the sensitivity and specificity of coagulation assays depend on the fibrinogen level as well as on the fibrinogen variant. In addition, patients suffering from CFD have a heterogeneous clinical course which is often unpredictable by routine coagulation assays. To better determine the patient's clinical phenotype, global hemostasis assays and an assessment of the fibrin clot properties are performed in research laboratories. In this review, we summarize the fibrinogen work-up highlighting some common pitfalls and provide an update of the research on CFD.

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A case of congenital afibrinogenemia with multiple thrombotic and hemorrhagic disorders

Wei

Tang

et al. 2022

Clinical Case Reports

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Perioperative management of a severe congenital hypofibrinogenemia with thrombotic phenotype

Cited by 26 publications

References 16 publications

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

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

From Routine to Research Laboratory: Strategies for the Diagnosis of Congenital Fibrinogen Disorders

A case of congenital afibrinogenemia with multiple thrombotic and hemorrhagic disorders

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