Platelet plug microstructure and flow modulate fibrin gelation dynamics: Insights from computational simulations

Area of Science:

• Biophysics
• Computational Biology
• Hematology

Background:

• Thrombus formation involves heterogeneous platelet aggregation and fibrin network stabilization.
• The interplay between platelet microstructure, blood flow, and fibrin development remains unclear.

Purpose of the Study:

• To investigate how platelet-plug microstructure and flow dynamics jointly regulate fibrin formation during thrombus development.
• To explore the mechanistic trade-offs between rapid vessel sealing and durable thrombus stabilization.

Main Methods:

• Development of a novel 2D computational framework integrating platelet aggregation, a reduced coagulation model, and a fibrin polymerization model.
• Simulation of three distinct platelet-plug configurations under various wall shear rates.
• Quantification of spatiotemporal clotting metrics, including factor concentrations, fibrin evolution, and gelation onset.

Main Results:

• Gelation initiation accelerated with increasing platelet plug density.
• Dense plugs showed peripheral gelation, with restricted intraplug transport and increased localized thrombin.
• Loose plugs facilitated deeper fibrinogen replenishment, initiating gelation at the vessel wall despite slower initial coagulation.

Conclusions:

• Platelet plug densification, while promoting rapid sealing, can impede intraplug fibrin formation necessary for long-term stability.
• The study provides a computational basis for understanding platelet-coagulation interactions under flow.
• Findings have implications for therapeutic strategies targeting cardiovascular disease prevention.