Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen

TLDR

The study evaluated thrombus growth in mice lacking von Willebrand factor and fibrinogen, the two key ligands for platelet adhesion and aggregation. Intravital microscopy of ferric chloride–injured arterioles in live mice was used to observe platelet plug formation. vWF–/– mice showed delayed platelet adhesion yet formed stable thrombi, Fg–/– mice produced abundant but detaching thrombi causing downstream occlusion, and vWF–/–Fg–/– mice formed thrombi with mixed characteristics that occluded most vessels, with platelet α‑granules enriched in fibronectin indicating a potential alternative aggregation ligand.

Abstract

We used intravital microscopy to observe the formation of platelet plugs in ferric chloride–injured arterioles of live mice. With this model, we evaluated thrombus growth in mice lacking von Willebrand factor (vWF) and fibrinogen (Fg), the two key ligands known to mediate platelet adhesion and aggregation. In vWF–/– mice, despite the presence of arterial shear, delayed platelet adhesion occurred and stable thrombi formed. In many mice, a persisting high-shear channel never occluded. Abundant thrombi formed in Fg–/– mice, but they detached from the subendothelium, which ultimately caused downstream occlusion in all cases. Surprisingly, mice deficient in both vWF and Fg successfully formed thrombi with properties characteristic of both mutations, leading to vessel occlusion in the majority of vessels. Platelets of these doubly deficient mice specifically accumulated fibronectin in their α-granules, suggesting that fibronectin could be the ligand supporting the platelet aggregation.