Diagnosis and Classification of Congenital Fibrinogen Disorders Fibrinogen and FXIII SSC

Diagnosis and classification of congenital fibrinogen disorders Fibrinogen and FXIII SSC

Person responsible: Chair, Verena Schroeder; Principal Investigator Alessandro Casini

Description Abstract

Congenital fibrinogen disorders (CFD) are a heterogeneous group of rare inherited coagulation defects. CFD results from monoallelic and biallelic mutations in FGA, FGB and FGG genes. The spectrum of molecular anomalies is broad, leading to several subtypes of fibrinogen disorders (i.e, afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, hypodysfibrinogenemia). The diagnosis of CFD is mainly based on standard clotting times. Many fibrinogen assays are available with a large variability according to the methods and time required. The sensitivity of coagulation tests is dependent on reagents, coagulometers and also on fibrinogen variants. This heterogeneity has recently been highlighted by a multicentre study involving the United Kingdom National External Quality Assessment Service and prospective Rare Bleeding Diseases Database laboratories. Global hemostatic assays, functional assays, and structural analyses are emerging tools performed mostly in research laboratories. To date there are no recommendations for the biological assessment of inherited fibrinogen disorders, taking especially into consideration all the new tests available.

In this guidance project, we aim to propose a screening test strategy for CFD reviewing the available “standard” and “specialised” assays for fibrinogen assessment. In addition, we would like to suggest a classification of CFD according to the fibrinogen levels as well as to the clinical phenotype in order to better standardise the identification, the description and the classification of CFD.

Design and methodology:

Study population:

Expected timeline:

Proposal 02.2018; writing 03.-06.2018; presentation to ISTH SSC 07.2018; submission to Guidelines and Guidance Committee 09.2018

Expected outcomes:

Publication as Guidance document

Description of project set/up and management, needed infrastructure and resources:

The writing group will include Alessandro Casini, Philippe de Moerloose, Anetta Undas and Jecko Thachil

Possible references:

Jennings I, Kitchen S, Menegatti M, Palla R, Walker I, Peyvandi F, Makris M. Potential misdiagnosis of dysfibrinogenaemia: Data from multicentre studies amongst UK NEQAS and PRO-RBDD project laboratories. Int J Lab Hematol. 2017;39:653-662.

Casini A, Blondon M, Lebreton A, Koegel J, Tintillier V, de Maistre E, Gautier P, Biron C, Neerman-Arbez M, de Moerloose P. Natural history of patients with congenital dysfibrinogenemia. Blood 2015; 125: 553-61

Neerman-Arbez M, de Moerloose P, Casini A. Laboratory and Genetic Investigation of Mutations Accounting for Congenital Fibrinogen Disorders. Semin Thromb Hemost 2016; 42: 356-65.

Undas A. How to Assess Fibrinogen Levels and Fibrin Clot Properties in Clinical Practice? Semin Thromb Hemost 2016; 42: 381-8.

Mackie IJ, Kitchen S, Machin SJ, Lowe GD; Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. Guidelines on fibrinogen assays.Br J Haematol. 2003;121:396-404.