PB0171 - Phenotypic Classification and Genetic Mutations in Congenital Fibrinogen Deficiencies: Insights from a Retrospective Cohort of a Single Center

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Huacong Cai, MD

associate Professor
Department of Hematology，Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Beijing, Beijing, China (People's Republic)

Co-Author(s)

sw

shujie wang

Professor
Department of Hematology，Peking Union Medical College Hospital, Chinese Academy
beijing, Beijing, China (People's Republic)
TZ

Tienan Zhu

Professor
Department of Hematology，Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
beijing, Beijing, China (People's Republic)
YZ

Yongqiang Zhao

Professor
Department of Hematology，Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
beijing, Beijing, China (People's Republic)
WS

Weiling ShOU

associate Professor
Department of Hematology，Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Beijing, Beijing, China (People's Republic)
KL

Kuixing Li

associate Professor
Department of Hematology，Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Beijing, Beijing, China (People's Republic)

Background: Congenital fibrinogen deficiencies (CFDs) are inherited disorders affecting fibrinogen synthesis and function, causing varying hemostatic issues. The genetic diversity and clinical effects in CFDs, especially in heterogeneous cohorts, are not fully explored.

Aims: The aim of this study was to delineate the genetic mutations, clinical manifestations, and laboratory diagnostic characteristics of patients with CFD at a single medical center.

Methods: We conducted a retrospective cohort study, analyzing clinical data from 124 patients diagnosed with CFD at Peking Union Medical College Hospital from January 2017 to September 2023. Phenotypes were classified based on fibrinogen activity, antigen levels, and genetic mutation profiles.

Results: The study included 124 patients (45 males and 79 females), with a median age of 34.5 years. Detailed subgroup analysis identified 2 cases of afibrinogenemia, 16 of hypofibrinogenemia, 4 of hypodysfibrinogenemia, and 71 of dysfibrinogenemia. Median fibrinogen activity (FIB:C) were 1.06 g/L, 0.48 g/L, and 0.33 g/L for the hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia groups, respectively. The FIB:C ratios were considerably lower in the dysfibrinogenemia and hypodysfibrinogenemia groups compared to those with hypofibrinogenemia(see Table 1). Clinically, 37 out of 124 patients (29.8%) experienced one or more hemorrhagic episodes, predominantly oral hemorrhage and menorrhagia. The median ISTH-BAT score was 1 (range 0-7). Thrombotic events were recorded in 9 patients (7.3%), encompassing cerebral infarction and deep vein thrombosis, whereas 63.7% of the cohort remained asymptomatic. Genetic screening performed on 94 subjects identified 102 mutations spanning the trio of fibrinogen genes. Missense mutations accounted for 86.3%, with 57 unique FGG mutations and 25 novel mutations (see Figure 1).

Conclusion(s): The majority of patients presenting with markedly reduced FIB: C levels ( < 0.5 g/L) were diagnosed with dysfibrinogenemia and were either asymptomatic or had minor bleeding symptoms. However, those with afibrinogenemia showed more profound hemorrhagic complications, indicating a need for close clinical monitoring.