Abstract
Introduction Emicizumab prophylaxis improves coagulation function in congenital hemophilia A,
regardless of inhibitor presence. We recently reported that emicizumab enhanced the
coagulant potentials, ex vivo, in plasmas from patients with acquired hemophilia A
(PwAHAs) at diagnosis. However, coagulant effects of emicizumab in PwAHAs during the
clinical course remain unclear.
Aim To assess ex vivo coagulant effects of emicizumab in PwAHAs during the clinical course.
Methods/Results Blood samples were obtained from 14 PwAHAs on (median) days 0 and 6 during a severe-bleeding
phase, and days 27 and 59 during a reduced-bleeding phase with elevated endogenous
factor VIII (FVIII) and decreased inhibitor titers. If administered a single dose
of 3 or 6 mg/kg, or two doses at 6 mg/kg followed by 3 mg/kg, estimated plasma emicizumab
concentrations (10/5/2.5, 20/10/5, and 30/15/7.5 µg/mL on days 0–7/30/60, respectively)
could be used to represent potential changes, based on the half-life (T
1/2: ∼30 days). Emicizumab concentrations that covered maximum plasma concentrations
of each dosage were used for spiking on day 0. Ex vivo addition of estimated emicizumab
to PwAHA's plasma containing endogenous FVIII and/or inhibitor, without and with recombinant
(r)FVIIa administration during immunosuppressive therapy, increased the calculated
Ad|min1| values, assessed by clot waveform analysis, and their coagulant potentials
were below normal levels. Rotational thromboelastometry revealed that ex vivo emicizumab
addition resulted in the further improvement of coagulant potentials in whole bloods
when combined with rFVIIa administration.
Conclusion Based on ex vivo and in vitro data, emicizumab has the potential to be effective
in clinical situations for PwAHAs.
Keywords
bispecific - acquired hemophilia A - autoantibodies - pharmacokinetic - coagulation
