In vitro rescue of FGA deletion by lentiviral transduction of an afibrinogenemic patient's hepatocytes

Stroka, Deborah; Keogh, Adrian; Vu, Dung; Fort, Alexandre; Stoffel, Michael; Kühni-Boghenbor, Kathrin; Furer, Cynthia; Banz, Vanessa; Biasiutti, Franziska Demarmels; Lämmle, Bernhard; Candinas, Daniel; Neerman-Arbez, Marguerite

doi:10.1111/jth.12714

Cited by 5 publications

(6 citation statements)

References 17 publications

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“…4 A potential therapeutic approach for selected cases of congenital afibrinogenemia could be liver transplantation, which has been successfully performed in two afibrinogenemic patients, one with a Budd-Chiari syndrome 80 and the other with recurrent thrombosis concomitant to life-threatening hemorrhages. 81 The management of thrombosis is often challenging, as it is necessary to give both antithrombotic drugs and fibrino-gen concentrate at the same time. It has been reported that the increased circulating levels of prothrombin fragment 1 þ 2 and thrombin-antithrombin complexes, abnormally elevated in afibrinogenemia, can be normalized by fibrinogen infusion.…”

Section: Management Of 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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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: Management Of 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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“…This report represents one of only three published cases of congenital afibrinogenemia that had undergone successful OLT .…”

Section: Coagulation Profilementioning

confidence: 91%

“…(this second reporting survival 7 years posttransplant) [8], it is possible to perform safely an OLT in patients with congenital afibrinogenemia and it represents a potential cure for the underlying fibrinogen deficiency.…”

mentioning

confidence: 84%

“… and Stroka et al . (this second reporting survival 7 years posttransplant) , it is possible to perform safely an OLT in patients with congenital afibrinogenemia and it represents a potential cure for the underlying fibrinogen deficiency. Transplant may be better justified in those with serious thrombotic history and risk for catastrophic bleeding.…”

Section: Coagulation Profilementioning

confidence: 99%

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Resolution of fibrinogen deficiency in a patient with congenital afibrinogenemia after liver transplantation

2015

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“…In case patients were reported more than once, only the most comprehensive publication was included. We did not include a previous publication on patient A2 of our case series (8). No quality assessment was conducted as quality was expected to be low and an established quality assessment tool for case reports does not exist.…”

Section: Systematic Reviewmentioning

confidence: 99%

Thromboembolism in patients with congenital afibrinogenaemia

Nagler¹,

Hovinga²,

Alberio³

et al. 2016

Thromb Haemost

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Frequent arterial and venous thromboembolism in patients with congenital afibrinogenaemia (CA) is neither understood nor is a safe and effective treatment established. It was our objective to report on the clinical observations and laboratory data contributing to the understanding of the frequency, physiopathology, prognosis and treatment of CA. We observed the long-term clinical course and laboratory data in a cohort of four patients with CA and thromboembolic complications, and conducted a systematic review retrieving all available data. Four patients with CA developed recurrent and extensive arterial and venous thromboembolism (TE) from an age of 25-51 years. In two patients, a treatment strategy targeting at maintaining constantly measurable fibrinogen (Fbg) levels (≥0.5 g/l) either by regular Fbg replacement or by orthotopic liver transplantation resulted in long-term remissions. Radiological imaging documented resolved arterial thrombi after 6-12 months. In contrast, recurrent thromboembolic events were observed in two other patients with infrequent Fbg replacement. A systematic review of the literature revealed 48 reports of TE in patients with CA (median age at first event 31 years), and a favourable outcome in most patients with frequent application of Fbg, aimed at constantly measurable trough levels. Present data suggests that patients with CA are at high risk of arterial and venous thromboembolic events, probably caused by thrombin excess owing to lack of thrombin scavenging by Fbg/fibrin. Regular low-dose Fbg replacement might be a safe and effective treatment option in patients with CA and thromboembolic complications.

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In vitro rescue of FGA deletion by lentiviral transduction of an afibrinogenemic patient's hepatocytes

Cited by 5 publications

References 17 publications

Clinical Features and Management of Congenital Fibrinogen Deficiencies

Clinical Features and Management of Congenital Fibrinogen Deficiencies

Resolution of fibrinogen deficiency in a patient with congenital afibrinogenemia after liver transplantation

Thromboembolism in patients with congenital afibrinogenaemia

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