The clearance rates of endogenous plasma von Willebrand factor (VWF) determine the half-life of factor VIII (FVIII) in patients with hemophilia, according to a new study published in the Journal of Thrombosis and Haemostasis.
“Based on our data, we hypothesize that to achieve optimal protection against [hemophilic arthropathy], individual FVIII clearance rates may need to be determined early in life, ideally at the beginning of prophylaxis in children,” the study’s authors said.
They observed marked heterogeneity in both recombinant FVIII (rFVIII) half-life and clearance rate in the study cohort. The rFVIII half-life varied from 7.7 hours to 20.1 hours (median, 11.3 hours), whereas the rFVIII clearance rate varied from 0.018 to 0.067 dL/h/kg (median, 0.037 dL/h/kg).
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The estimated half-life of endogenous plasma VWF in patients with hemophilia was significantly correlated with the half-life of infused rFVIII.
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Moreover, the ABO blood group had a significant effect on plasma VWF levels. Patients in the non-O blood group had significantly higher VWF:Ag levels than those with blood group O. On the other hand, patients with blood group O had higher rFVIII half-life and higher VWF propeptide (VWFpp)/VWF:Ag ratio than those in the non-O blood group.
The researchers also found a correlation between age and rFVIII half-life. Increasing age was associated with a progressive increase in plasma VWF:Ag levels and a decrease in rFVIII clearance rates. Futhermore, there was a trend toward decreasing VWFpp/VWF:Ag ratio with advancing age.
The study enrolled 61 participants, including 55 individuals with severe hemophilia A and 6 with moderate hemophilia A, who received treatment with an antihemophilic factor octocog alfa (Advate®) with a standard half-life. Most patients (n=52) were maintained on regular prophylaxis, while 9 patients received on-demand treatment.
Reference
Elsheikh E, Lavin M, Heck LA, et al. Heterogeneity in the half-life of factor VIII concentrate in patients with hemophilia A is due to variability in the clearance of endogenous von Willebrand factor. J Thromb Haemost. Published online January 20, 2023. doi:10.1016/j.jtha.2023.01.013
