PB1140 - Laboratory features and genotype of a family with heritable dysfibrinogenaemia (HD)

Background: HD is a rare qualitative disorder of fibrinogen. Subjects are asymptomatic (55%), experience abnormal bleeding (25%) or trombosis (20%). Diagnosis is based on reduced Clauss fibrinogen (CF), normal quantitative fibrinogen (QF), usually prolonged thrombin time (TT) and reptilase time (RT). PT and APTT are usually normal but sensitive depends on coagulometers and activators used. Subjects are better identified with genotype, HD has been linked to more than 100 pathogenic nucleotide variations.

Aims: Determine clinical phenotype, laboratory features and genotype in a family with HD identified at our centre

Methods: A patient with history of central retinal vein occlusion (CRVO) was diagnossed of HD because of a thrombophilia test, rotational-thromboelastometry was assessed and diagnosis was confirmed by QF and genotype. We studied the family, relatives with HD were clinical evaluated.
Samples were analysed using Sysmex coagulometer CS-2500 reagents (PT- Tromborel, APTT- Actin FS, TT- Thromboclotin, RT-Batroxobin, CF-Thrombin). QF with Nephelometry reagent Siemens N Antiserum to Human fibrinogen. Genotype with NGS NextSeq 1000 sequencing system (Illumina) analysing 3 fibrinogen exons with KIT Twist HCExome_V2.

Results: The results of the coagulation assays are summarised in table 1. Rotational-thromboelastometry was almost normal (Fig 1). The genotye in all HD subjects was variant FGG c.902G>A p. (Arg301His), previosly reported, in autosomal dominant pattern. All HD relatives were asymptomatic. The family had antecedents of a consanguineous marriage.

Conclusion(s): ⁻ The detection of HD in our case is casual, there is no evidence to suggest association with CRVO, even more so considering that all HD relatives are asymptomatic.
⁻ HD is underdiagnosed for usually lack of symptoms and normal basic coagulation test. Global hemostatic assay such as rotational-thromboelastometry maybe a help for diagnosis and therapy guidance.
⁻ NGS is usefull to support the diagnosis in rare diseases. Genotype–phenotype correlations would be of help to better estimate the risk of the patient.