NXT007-mediated hemostatic potential is suppressed by activated protein C-catalyzed inactivation of activated factor V.

ABSTRACT:

Background

Activated protein C (APC) inactivates activated factor (F) V (FVa) and FVIIIa. NXT007, an emicizumab-based engineered therapeutic bispecific antibody, enhances the coagulation potential of FVIII-deficient plasma (FVIIIdef-plasma) to near normal levels. However, little is known about the effect of APC-induced inactivation in NXT007-mediated hemostatic function.

Objectives

To investigate the contribution of APC-mediated reactions to NXT007-driven hemostasis.

Methods

In pooled normal plasma (PNP) or FVIIIdef-plasma spiked with NXT007 (10 μg/mL), effects of APC (0-16 nM) were measured using a thrombin generation assay (TGA). The direct effects of APC on cofactor activity of NXT007 or FVIIIa in a FXa generation assay were also measured. The FVdef-plasma and FV L

SUBMITTER: Nakajima Y 

PROVIDER: S-EPMC10727940 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature