Royal College of Surgeons in Ireland
Biological mechanisms underlying.....pdf (557.45 kB)

Biological mechanisms underlying inter-individual variation in factor VIII clearance in haemophilia

Download (557.45 kB)
journal contribution
posted on 2021-04-28, 16:11 authored by Peter L Turecek, Jill M Johnsen, Steven W Pipe, James O'DonnellJames O'Donnell, iPATH Study Group
Previous studies have highlighted marked inter-individual variations in factor VIII (FVIII) clearance between patients with haemophilia (PWH). The half-life of infused FVIII has been reported to vary from as little as 5.3 hours in some adult PWH, up to as long as 28.8 hours in other individuals. These differences in clearance kinetics have been consistently observed using a number of different plasma-derived and recombinant FVIII products. Furthermore, recent studies have demonstrated that half-life for extended half-life (EHL-) FVIII products also demonstrates significant inter-patient variation. Since time spent with FVIII trough levels <1% has been shown to be associated with increased bleeding risk in PWH on prophylaxis therapy, this variability in FVIII clearance clearly has major clinical significance. Recent studies have provided significant novel insights into the cellular basis underlying FVIII clearance pathways. In addition, accumulating data have shown that endogenous plasma VWF levels, ABO blood group and age, all play important roles in regulating FVIII half-life in PWH. Indeed, multiple regression analysis suggests that together these factors account for approximately 34% of the total inter-individual variation in FVIII clearance observed between subjects with severe haemophilia A. In this review, we consider these and other putative modulators of FVIII half-life, and discuss the biological mechanisms through which these factors impact upon FVIII clearance in vivo.


Science Foundation (SFI) under the SFI Strategic Partnership Programme Grant number 16/SPP/3303

Shire US Inc



The original article is available at

Published Citation

Turecek PL, Johnsen JM, Pipe SW, O'Donnell JS; iPATH study group. Biological mechanisms underlying inter-individual variation in factor VIII clearance in haemophilia. Haemophilia. 2020;26(4):575-583

Publication Date

28 June 2020

PubMed ID



  • Irish Centre for Vascular Biology
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Vascular Biology




  • Published Version (Version of Record)