Hypofibrinogenemia and liver disease: a new case of Aguadilla fibrinogen and review of the literature

Casini, Alessandro; Sokollik, Christiane; Lukowski, Samuel W.; Lurz, Eberhard; Rieubland, Claudine; Moerloose, Philippe de; Neerman-Arbez, Marguerite

doi:10.1111/hae.12719

Cited by 22 publications

(19 citation statements)

References 34 publications

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“…21 This disorder, known as "Fibrinogen storage disease," is characterized by several degrees of liver inflammation and fibrosis as well as hypofibrinogenemia. 22 The underlying molecular mechanisms of the fibrin aggregates are not completely elucidated, but the promotion of aberrant intermolecular strand insertions and abnormal interactions between the functional domains of the fibrinogen gamma nodule are interesting hypotheses. 21,22 Preliminary results indicate a potential beneficial role of autophagy-enhancing drugs for the treatment of this disease.…”

Section: Afibrinogenemia and Hypofibrinogenemiamentioning

confidence: 99%

“…22 The underlying molecular mechanisms of the fibrin aggregates are not completely elucidated, but the promotion of aberrant intermolecular strand insertions and abnormal interactions between the functional domains of the fibrinogen gamma nodule are interesting hypotheses. 21,22 Preliminary results indicate a potential beneficial role of autophagy-enhancing drugs for the treatment of this disease. 23,24 Patients with quantitative fibrinogen disorders are also at risk of thrombosis.…”

Section: Afibrinogenemia and Hypofibrinogenemiamentioning

confidence: 99%

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Clinical Features and Management of Congenital Fibrinogen Deficiencies

Casini

Moerloose

Neerman-Arbez

2016

Semin Thromb Hemost

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Congenital fibrinogen disorders are rare diseases affecting either the quantity (afibrinogenemia and hypofibrinogenemia) or the quality (dysfibrinogenemia) or both (hypodysfibrinogenemia) of plasmatic fibrinogen. Afibrinogenemia is often diagnosed at birth following prolonged umbilical cord bleeding and is characterized by spontaneous bleeding in all tissues, while hypofibrinogenemic patients are more often asymptomatic. Spontaneous spleen ruptures, painful bone cysts, cardiovascular events, and intrahepatic inclusions can complicate the clinical course of patients with quantitative fibrinogen disorders. Clinical manifestations of dysfibrinogenemia are very heterogeneous, from absence of symptoms to major bleeding or thrombosis, chronic thromboembolic pulmonary hypertension, and renal amyloidosis. Hypodysfibrinogenemic patients can suffer from both major bleeding and recurrent thrombosis. Pregnancy of women with congenital fibrinogen disorders is a high-risk situation. Owing to the absence of controlled randomized studies, clinical management is mainly based on expert consensus. For the treatment and/or the prevention of bleeding, plasma-derived fibrinogen concentrates are the optimal choice. Treatment of thrombosis may be challenging. More specifically, management strategies should be tailored to each patient, taking the personal and familial history of bleeding and thrombosis, the genotype, and the specific clinical situation into account.

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Section: Afibrinogenemia and Hypofibrinogenemiamentioning

confidence: 99%

Section: Afibrinogenemia and Hypofibrinogenemiamentioning

confidence: 99%

Clinical Features and Management of Congenital Fibrinogen Deficiencies

Casini

Moerloose

Neerman-Arbez

2016

Semin Thromb Hemost

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“…Evaluation of liver function, including invasive measurements such as liver biopsy, is necessary in case of suspected hepatic storage disease (see below). 10 Diagnosis of congenital qualitative disorders may be more challenging, as the sensitivity of the coagulation tests is dependent on methods, reagents, and coagulometers. 11 In a series of 27 patients, the PT-derived method overestimated the fibrinogen coagulation capacity by approximately five to six times compared with the Clauss method, regardless of the testing equipment or the reagents.…”

Section: Laboratory Diagnosis Of Congenital Fibrinogen Disorders Stanmentioning

confidence: 99%

“…Only six mutations in FGG, all occurring within or near polymerization pocket hole "a," are known so far to cause hepatic storage disease. 10,[44][45][46][47][48] Genetic analysis of such patients should therefore start with the screening of FGG exons 8 and 9.…”

Section: Genetic Diagnosis Of Congenital Fibrinogen Disordersmentioning

confidence: 99%

Laboratory and Genetic Investigation of Mutations Accounting for Congenital Fibrinogen Disorders

Neerman-Arbez

Moerloose

Casini

2016

Semin Thromb Hemost

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Congenital fibrinogen disorders are classified into two types of plasma fibrinogen defects: type I (quantitative fibrinogen deficiencies), that is, hypofibrinogenemia or afibrinogenemia, in which there are low or absent plasma fibrinogen antigen levels, respectively, and type II (qualitative fibrinogen deficiencies), that is, dysfibrinogenemia or hypodysfibrinogenemia, in which there are normal or reduced antigen levels associated with disproportionately low functional activity. These disorders are caused by mutations in the three fibrinogen-encoding genes FGA, FGB, and FGG. Afibrinogenemia is associated with mild to severe bleeding, whereas hypofibrinogenemia is often asymptomatic. For these quantitative disorders, the majority of mutations prevent protein production. However, in some cases, missense or late-truncating nonsense mutations allow synthesis of the mutant fibrinogen chain, but intracellular fibrinogen assembly and/or secretion are impaired. Qualitative fibrinogen disorders are associated with bleeding, thrombosis, or both thrombosis and bleeding, but many dysfibrinogenemias are asymptomatic. The majority of cases are caused by heterozygous missense mutations. Here, we review the laboratory and genetic diagnosis of fibrinogen gene anomalies with an updated discussion of causative mutations identified.

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“…Since the first report of FSD due to FGG mutation [ 2 ], FSD has been found in Europe, America, Japan, Saudi Arabia, and Turkey [ 3 – 11 ], but not in China. Data on medical management of FSD are few [ 10 , 12 , 13 ]; carbamazepine (CBZ) and ursodeoxycholic acid (UDCA) may be useful [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Fibrinogen storage disease in a Chinese boy with de novo fibrinogen Aguadilla mutation: Incomplete response to carbamazepine and ursodeoxycholic acid

et al. 2016

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BackgroundFibrinogen storage disease (FSD) is a rare autosomal-dominant disorder caused by mutation in FGG, encoding the fibrinogen gamma chain. Here we report the first Han Chinese patient with FSD, caused by de novo fibrinogen Aguadilla mutation, and his response to pharmacologic management.Case presentationEpistaxis and persistent clinical-biochemistry test-result abnormalities prompted liver biopsy in a boy, with molecular study of FGG in him and his parents. He was treated with the autophagy enhancer carbamazepine, reportedly effective in FSD, and with ursodeoxycholic acid thereafter. Inclusion bodies in hepatocellular cytoplasm stained immune-histochemically for fibrinogen. Selective analysis of FGG found the heterozygous mutation c.1201C > T (p.Arg401Trp), absent in both parents. Over more than one year’s follow-up, transaminase and gamma-glutamyl transpeptidase activities have lessened but not normalized.ConclusionThis report expands the epidemiology of FSD and demonstrates idiosyncrasy in response to oral carbamazepine and/or ursodeoxycholic acid in FSD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-016-0507-3) contains supplementary material, which is available to authorized users.

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Hypofibrinogenemia and liver disease: a new case of Aguadilla fibrinogen and review of the literature

Cited by 22 publications

References 34 publications

Clinical Features and Management of Congenital Fibrinogen Deficiencies

Clinical Features and Management of Congenital Fibrinogen Deficiencies

Laboratory and Genetic Investigation of Mutations Accounting for Congenital Fibrinogen Disorders

Fibrinogen storage disease in a Chinese boy with de novo fibrinogen Aguadilla mutation: Incomplete response to carbamazepine and ursodeoxycholic acid

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