Mesoscale Simulations of Thrombin Activation and Fibrin Formation in Microvascular and In Vitro Settings

TL;DR

This study develops a mesoscale simulation framework to analyze thrombin activation and fibrin formation in microvascular and in vitro environments, integrating reaction kinetics with fluid transport for improved thrombosis understanding.

Contribution

It introduces a mesoscale particle-based model embedding reduced coagulation networks within flow fields, enabling detailed analysis of thrombin and fibrin dynamics in complex geometries.

Findings

The framework accurately reproduces thrombin generation curves under physiological conditions.

Variations in fibrinogen levels significantly influence thrombin and fibrin formation.

The model offers a unified approach to study biochemical kinetics and transport in blood coagulation.

Abstract

Blood coagulation is governed by tightly regulated reaction networks that unfold within a flowing, heterogeneous microvascular environment. Reduced kinetic models of the intrinsic and extrinsic pathways have seen limited in vitro validation, and their behavior within spatially resolved flow fields remains largely unexplored. Here, we embed two established reduced networks into a recently proposed mesoscale particle-based framework that resolves fluid momentum transport alongside multispecies advection-diffusion-reaction dynamics. We investigate the initiation phase of coagulation by simulating thrombin formation in microvascular geometries and in vitro assays, and we assess the framework's ability to reproduce thrombin generation curves (TGCs) under physiologically relevant conditions. We further examine how variations in fibrinogen levels - an important determinant of clot structure and a biomarker for inflammation and thrombosis - affect thrombin and fibrin formation. Overall, this study provides a unified computational approach for analysing how biochemical kinetics interact with transport processes, offering insights relevant to thrombosis modeling and blood diagnostics.