VPB1423 - Easy clot characteristics of the placenta in a case of congenital hypofibrinogenemia．

Background: We report a case of congenital hypofibrinogenemia (Fbg) in which three embryo transfers were performed in a case of artificial insemination failure, pregnancy was achieved, and the child was born with regular replacement therapy.

Aims: To investigate the thrombogenicity of the new gene mutation, we examined it in pathological specimens.

Methods: The patient was 38-year-old female. She was referred to us for embryo transfer after multiple failed artificial insemination attempts, and successfully conceived, delivered, and gave birth twice with replacement therapy with a dried human Fbg preparation as reported in this conference 2021. Genetic analysis of the DNA sequence of the PCR products in the Aα, Bβ, and γ chains revealed that the nucleotides in the γ chain exon8 were heterozygous for TGT (normal and wild type) and CGT (mutant type); Cys (cysteine; normal and wild type) was replaced by Arg (arginine; mutant type). Cys (cysteine; normal and wild type) was replaced by Arg (arginine; mutant), and no existing report was found [γp.C352R(Niigata II)]. After two deliveries, we examined the placental pathology in detail, and found that there were many thrombi in the placental blood vessels, which was clearly different from normal deliveries.

Results: In the Human fibrinogen database-Groupe d'etude sur l'hemostase et la thrombose (geht.org), previously reported mutations and the presence or absence of thrombotic tendency are described in detail, but there are many mutations with unknown thrombotic tendency. There are many mutations with unknown thrombogenicity. The new γp.C352R (Niigata II) is a mutation that may cause easy thrombosis during replacement therapy with dried human Fbg.

Conclusion(s): In this case, placenta with Fbg >150mg/dL at implantation and >100mg/dL during pregnancy under regular supplementation of dried human fibrinogen showed a tendency to thrombus. Further study will be necessary to study the optimal target Fbg concentration during pregnancy and delivery in cases with similar mutations.