Examining downstream effects of concizumab in hemophilia A with a mathematical modeling approach.

ABSTRACT:

Background

Tissue factor (TF) pathway inhibitor (TFPI) is an anticoagulant protein that inhibits factor (F)Xa, the TF-FVIIa-FXa complex, and early forms of the prothrombinase complex. Concizumab is a monoclonal antibody that blocks FXa inhibition by TFPI and reduces bleeding in hemophilia.

Objectives

To examine how concizumab impacts various reactions of TFPI to restore thrombin generation in hemophilia A using mathematical models.

Methods

A compartment model was used to estimate plasma concentrations of free concizumab and its complexes with TFPIα and TFPIβ. Concizumab was integrated into a flow-mediated mathematical model of coagulation, and a small injury was simulated under hemophilia A conditions. Simulations were then analyzed to determine how concizumab's block

SUBMITTER: Miyazawa K 

PROVIDER: S-EPMC12336664 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature