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Thromb Haemost 2016; 116(04): 722-732
DOI: 10.1160/TH16-02-0082
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Thromboembolism in patients with congenital afibrinogenaemia

Long-term observational data and systematic review
Michael Nagler
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
2   Department of Clinical Research, University of Bern, Bern, Switzerland
,
Johanna A. Kremer Hovinga
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
2   Department of Clinical Research, University of Bern, Bern, Switzerland
,
Lorenzo Alberio
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
3   Service of Hematology and Central Hematology Laboratory, CHUV, University of Lausanne, Lausanne, Switzerland
,
Kristiina Peter-Salonen
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
,
Hendrik von Tengg-Kobligk
4   Institute for Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern University Hospital, Bern, Switzerland
,
Daniel Lottaz
2   Department of Clinical Research, University of Bern, Bern, Switzerland
,
Marguerite Neerman-Arbez
5   Department of Genetic Medicine and Development, University Medical Center, Geneva, Switzerland
,
Bernhard Lämmle
1   Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Bern, Switzerland
6   Center for Thrombosis and Hemostasis, University Medical Center, Mainz, Germany
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Publikationsverlauf

Received: 02. Februar 2016

Accepted after major revision: 02. Juni 2016

Publikationsdatum:
20. November 2017 (online)

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Summary

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.

Note: Preliminary data of this report were presented as oral presentation at the XXV Congress of the International Society on Thrombosis and Haemostasis, June 20th to 25th, Toronto, Canada.

Supplementary Material to this article is available online at www.thrombosis-online.com.

Keywords

Afibrinogenaemia - venous thromboembolism - thrombosis - aortic disease - arterial occlusive disease - peripheral vascular disease - fibrinogen

 

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