Universität zu Köln

Topuz, Alper ORCID: 0009-0004-5366-0173 (2026). Modeling Hemostasis and Thrombosis - In Silico Prediction of Dynamics of Blood Clotting. PhD thesis, Universität zu Köln.

PDF (Alper Topuz Doctoral Thesis) Topuz_Thesis.pdf - Accepted Version Bereitstellung unter der CC-Lizenz: Creative Commons Attribution. Download (11MB)

Abstract

Hemostasis is an essential physiological process that prevents blood loss following vascular injury, yet its dysregulation can lead to severe pathological outcomes. Thrombosis refers to clot formation in the absence of vascular injury and can lead to lethal consequences. These processes arise from a complex interplay between hydrodynamics, deformable blood cells, polymeric blood proteins, and force-dependent adhesive interactions occurring across multiple length and time scales. In this thesis, we develop and apply large-scale particle-based simulations to investigate the physical mechanisms governing blood clot and thrombus formation under flow, with particular emphasis on the coupling between hydrodynamics, cellular mechanics, and adhesive bond kinetics. Blood plasma is modeled as a viscous fluid; red blood cells and platelets as deformable or rigid particles; and von Willebrand factor (vWF) as a polymeric macromolecule whose conformation and adhesive activity are regulated by hydrodynamic forces. By explicitly resolving individual blood components, the simulations enable a multi-scale investigation of how microscale interactions give rise to emergent collective macro-scale behavior in flowing blood. The first part of this work focuses on the formation and dynamics of platelet–vWF aggregates in blood flow. We examine the conditions under which aggregates form, migrate, remain stable, or dissociate, and distinguish between reversible and irreversible aggregation mechanisms. The results demonstrate that aggregate behavior is governed by the combined effects of hydrodynamic interactions, margination, and force-dependent bond lifetimes. In particular, bond kinetics play a decisive role in controlling whether aggregates persist as they migrate away from the vessel wall toward the channel center, where shear rates are reduced, or undergo dissociation. By systematically comparing different adhesive bond models, including catch-slip and slip-only kinetics, we identify physical regimes in which transient or stable aggregates emerge in flowing blood. Building on these insights, the second part of the thesis presents an in silico model of primary hemostasis at a site of vascular injury. The simulations capture the accumulation of platelets and vWF at a hemostatic site that mimics a damaged vessel wall and follow the time-dependent formation, growth, and embolization of a hemostatic plug under physiologically relevant high-shear flow conditions. We analyze clot geometry, internal structure, and mechanical stability, and characterize distinct phases of clot evolution, including growth, deformation, and embolization events. The results highlight early stages of primary hemostasis that remain poorly understood. Overall, this work provides a mechanistic, physics-based perspective on blood clotting dynamics and demonstrates how mesoscale simulations can bridge microscopic interactions and macroscopic hemostatic outcomes.

Item Type:	Thesis (PhD thesis)
Creators:	Creators Email ORCID ORCID Put Code Topuz, Alper topuz.alper95@gmail.com https://orcid.org/0009-0004-5366-0173 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-804599
Date:	2026
Place of Publication:	KUPS
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Außeruniversitäre Forschungseinrichtungen > Forschungszentrum Jülich
Subjects:	Natural sciences and mathematics Physics
Uncontrolled Keywords:	Keywords Language Primary Hemostasis English Blood Clotting English Hemostatic Plug English SDPD English Mesoscale English Bleeding English UNSPECIFIED English
Date of oral exam:	17 April 2026
Referee:	Name Academic Title Fedosov, Dmitry A. PD Dr. Schadschneider, Andreas Prof. Dr. Schmidt, Annette M Prof. Dr.
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80459