PB0173 - Clinical, laboratory and genetic analysis of 13 Chinese patients with symptomatic congenital hypodysfibrinogenemia

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Liyang Zhou, PhD student in medicine

Graduate student
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai, Shanghai, China (People's Republic)

Co-Author(s)

Haoyang Wu

Ph.D. student
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
Shanghai, Shanghai, China (People's Republic)
Ziqi Zhang

postgraduate
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Shanghai, Shanghai, China (People's Republic)
GC

Guangming Chen

Graduate student
Shanghai Jiaotong Unicersity School of Medicine
Shanghai, Shanghai, China (People's Republic)
YM

Yinqi Mao

Ruijin Hospital, No. 197 Ruijin Second Road, Huangpu District, Shanghai
Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai, China (People's Republic)
WW

Wenman Wu

Professor
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
Shanghai, Shanghai, China (People's Republic)
JD

Jing Dai

Professor
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
Shanghai, Shanghai, China (People's Republic)
XW

Xuefeng Wang

Professor
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
Shanghai, Shanghai, China (People's Republic)
QD

Qiulan Ding

Professor
Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Shanghai, Shanghai, China (People's Republic)

Background: Congenital hypodysfibrinogenemia, a rare fibrinogen disorder caused by variants in three fibrinogen genes, is characterized by dysfunctional and low levels of fibrinogen. Patients are often symptomatic with bleeding or thrombosis.

Aims: To investigate the clinical, laboratory features and genotypic spectrum of 13 symptomatic patients with congenital hypodysfibrinogenemia.

Methods: 13 unrelated patients were included in this study. Fibrinogen functional activity (Fg:C) and its antigen level (Fg:Ag) were measured by Clauss method and immunoturbidimetric assay, respectively. Whole exome sequencing was used for mutation screening, and verified by sanger sequencing. SIFT, PolyPhen-2 and Mutation Taster were applied to determine the pathogenicity of novel variants. ISTH-BAT score was used to quantify the bleeding manifestations. Pearson's correlation was performed using IBM SPSS Statistics 24.

Results: Table1 shows the clinical phenotypes of 13 patients (10 with bleeding and 3 with thrombosis). Oral cavity bleeding, postpartum hemorrhage, easy bruising and menorrhagia were the most common bleeding symptoms. Among 3 patients with thrombosis, one patient presented with both venous and arterial thrombosis, while the other two patients suffered from arterial thrombosis only. No other thrombotic risk factors were observed. Twelve variants were identified, mostly (10/12) in FGA and FGG. Eight novel variants were identified and predicted pathogenic by three prediction tools: FGA p.C55Y, p.C68F; FGB p.C95R, p.T407R; FGG p.Y237C, p.W279R, p.Y300C, p.S358fs. Table 2 shows that Fg:C, Fg:Ag, or Fg:C/Fg:Ag were not correlated with ISTH-BAT score among bleeding patients.

Conclusion(s): Bleeding symptoms seem more serious in women than in men, while thrombosis appears to be more often in male patients and arterial thrombosis is common. Variant types and locations rather than fibrinogen level are more likely to be related to clinical phenotypes. Variants equivalent to residues in forming γ- nodule, b hole, and disulfide bonds would affect fibrinogen concentration and function, causing hypodysfibrinogenemia. Additional cysteines may be a reason to thrombosis.