title: Thromboembolism in patients with congenital afibrinogenaemia. Long-term observational data and systematic review.
abstract: 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Nagler
authors.affiliation: Johanna A. Kremer Hovinga, Department of Haematology and Central Haematology Laboratory, Inselspital University Hospital, 3010 Bern, Switzerland, Tel. +41 31 632 0265, Fax: +41 31 632 1882, E-mail: Johanna.Kremer@insel.ch.
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Kremer Hovinga
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Alberio
authors.forename: Kristiina
authors.initials: K
authors.lastname: Peter-Salonen
authors.forename: Hendrik
authors.initials: H
authors.lastname: von Tengg-Kobligk
authors.forename: Daniel
authors.initials: D
authors.lastname: Lottaz
authors.forename: Marguerite
authors.initials: M
authors.lastname: Neerman-Arbez
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lämmle
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000150:complications* / Q000151:congenital; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000150:complications*
keywords: Afibrinogenaemia; aortic disease; arterial occlusive disease; fibrinogen; peripheral vascular disease; thrombosis; venous thromboembolism