Factor VIII pharmacokinetics associates with genetic modifiers of VWF and FVIII clearance in an adult hemophilia A population.

Journal of Thrombosis and Haemostasis : JTH
Kenichi OgiwaraDavid Lillicrap

Abstract

Factor VIII (FVIII) pharmacokinetics (PK) in adult hemophilia A populations are highly variable and have been previously determined to be influenced by von Willebrand factor:antigen (VWF:Ag), ABO blood group, and age. However, additional genetic determinants of FVIII PK are largely unknown. The contribution of VWF clearance, VWF-FVIII-binding activity, and genetic variants in VWF clearance receptors to FVIII PK in adult patients were assessed. FVIII PK assessment was performed in 44 adult subjects (age 18-61 years) with moderate or severe hemophilia A. VWF:Ag, VWF propeptide (VWFpp), VWFpp/VWF:Ag, and VWF:FVIII binding activity were measured. The VWF modifying loci CLEC4M, SCARA5, STAB2, and ABO, and the D'D3 FVIII-binding region of the VWF gene were genotyped. VWF:Ag, VWFpp, and VWF:FVIIIB positively correlated with FVIII half-life and negatively correlated with FVIII clearance. VWFpp/VWF:Ag negatively correlated with FVIII half-life and positively correlated with FVIII clearance. The correlation between VWFpp/VWF:Ag and FVIII half-life was stronger for type non-O patients than for type O patients, suggesting that slower VWF clearance increases FVIII half-life. Patients heterozygous for the CLEC4M rs868875 variant had increase...Continue Reading

References

Oct 25, 1996·Forensic Science International : Synergy·J C LeeJ G Chang
Feb 24, 2001·Lancet·M de LangeP J Grant
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·S PöhlmannR W Doms
Dec 24, 2005·Journal of Thrombosis and Haemostasis : JTH·E M BladbjergJ Hjelmborg
May 11, 2006·Haemophilia : the Official Journal of the World Federation of Hemophilia·M LeeV Chamouard
Jan 11, 2007·Haemophilia : the Official Journal of the World Federation of Hemophilia·S BjörkmanE Berntorp
May 7, 2008·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ui-Soon KhooC L Steve Lin
Aug 25, 2010·Haemophilia : the Official Journal of the World Federation of Hemophilia·S Björkman
Dec 26, 2012·Proceedings of the National Academy of Sciences of the United States of America·Karl C DeschDavid Ginsburg
Jan 15, 2015·Haemophilia : the Official Journal of the World Federation of Hemophilia·S KepaI Pabinger
Feb 16, 2016·Journal of Thrombosis and Haemostasis : JTH·S AlbánezD Lillicrap
Aug 23, 2016·Expert Opinion on Emerging Drugs·Massimo Morfini, Ezio Zanon
Feb 11, 2018·Blood Reviews·H C A M HazendonkUNKNOWN OPTI-CLOT study group
Jul 8, 2018·Blood Advances·Ahmad H MuftiUNKNOWN European Group on von Willebrand disease (EU-VWD) and Zimmerman Program for the Molecular and Clinical Biology of von Willeb
Aug 21, 2018·The Journal of Clinical Investigation·Laura L SwystunDavid Lillicrap
Feb 12, 2019·Journal of Thrombosis and Haemostasis : JTH·Laura L SwystunDavid Lillicrap
May 6, 2019·Journal of Thrombosis and Haemostasis : JTH·Barbara LunghiMassimo Morfini
May 28, 2019·Journal of Thrombosis and Haemostasis : JTH·Laura L SwystunDavid Lillicrap

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Citations

Jun 25, 2021·Biologics : Targets & Therapy·Emanuela MarchesiniLeonard Valentino
Nov 17, 2021·Expert Opinion on Biological Therapy·Steven W PipeOscar G Segurado

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