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Poster Networking

Inherited Bleeding Disorders and Inhibitors

PB1209 - Investigation of genetic factors associated with the half-life of infused factor VIII in hemophilia A patients

Tuesday, June 25, 2024
13:45 – 14:45 ICT
Room: Exhibition Hall

    Presenting Author(s)

  • Hiroshi Inaba

    Associate Professor
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

    • Co-Author(s)

  • Keiko Shinozawa, PhD

    Assistant Professor
    Department of Laboratory Medicine, Tokyo Medical University/Japan
    Shinjuku-ku, Tokyo, Japan

  • AM

    Ayano Mitsuhashi

    Endowed researcher
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

  • SK

    Shun Kaneko

    Resident
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

  • YH

    Yuko Harada

    Resident
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

  • RM

    Ryui Miyashita

    Resident
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

  • YK

    Yoshiko Kamikubo

    Assistant Professor
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

  • TY

    Tomoko Yamaguchi

    Assistant Professor
    Department of Laboratory medicine, Tokyo Medical University
    ChuokuNihonbashiKodenmacho, Tokyo, Japan

  • AI

    Akito Ichiki

    Assistant Professor
    Department of Laboratory medicine, Tokyo Medical University
    Shinjukuku, Tokyo, Japan

  • YC

    Yushi Chikasawa

    Assistant professor
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku-ku, Tokyo, Japan

  • Masato Bingo, MD, PhD

    Assistant Professor
    Department of Laboratory medicine, Tokyo Medical University
    Shinjukuku, Tokyo, Japan

  • RS

    Ryoko Sekiya

    Assistant professor
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

  • TM

    Takashi Muramatsu

    Associate professor
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

  • MY

    Mihoko Yotsumoto

    Associate professor
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

  • TH

    Takeshi Hagiwara

    Associate professor
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

  • KA

    Kagehiro Amano

    Professor
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

  • EK

    Ei Kinai

    Professor
    Department of Laboratory Medicine, Tokyo Medical University
    Shinjuku, Tokyo, Japan

Background: In vivo half-life of blood coagulation factor VIII (FVIII) is thought to be influenced by ABO blood groups, age, von Willebrand factor (VWF) antigen levels, and receptors involved in VWF and FVIII clearance. However, this is not fully understood.

Aims: We aimed to obtain new insights into the genetic determinants of FVIII half-life by analyzing the genes and the half-life of infused FVIII in hemophilia A patients (PwHA).

Methods: We studied the PwHA who were outpatients of our hospital and had previously undergone a pharmacokinetic study (PK) as part of their medical care. This study was approved by the Medical Ethics Review Committee of Tokyo Medical University. The half-life of each PwHA's FVIII concentrates using was determined by analyzing their PK data using the population pharmacokinetic service (WAPPS-Hemo). For PwHA exhibiting distinct half-life profiles, we conducted genetic analyses of VWF and nine receptors (LRP1, LDLR, ASGP1, MRC1, SIGLEC5, CLEC4M, STAB2, SCARA5, HSPG2).

Results: We analyzed the half-life of 33 PwHA and found three patients with a longer half-life than the others. Patients 1 and 2 had a half-life of 19.5 and 25.5 hours for rurioctocog alfa, respectively, and patient 3 had a half-life of 31.75 hours for rurioctocog alfa pegol. The blood groups and VWF:Ag of each patient were type A 131%, type O 66%, and type B 187%, respectively. The results are shown in Table. Among the three patients analyzed, differences were observed in the rs868875 and VNTR of the CLEC4M gene. However, the determinants of their long half-life could not be identified during the study.

Conclusion(s): Genetic analysis of proteins potentially involved in FVIII half-life was performed in the three patients with long FVIII half-life. However, its features are not so simple and needs further analysis.