Arterial human blood flow can be stopped by cables of VWF and platelets without coagulation Open Access

• SIPA thrombi are built from platelet-VWF strings forming a strong transverse cable.

• VWF-VWF bonds are the weakest link in thrombus strength, making them key targets for clot lysis.

Arterial thrombi formed under high shear rates (~15,000/s) must withstand substantial forces to occlude arteries, as occurs in myocardial infarction or ischemic stroke, driving the need to understand the structural features responsible for their strength. We used scanning electron microscopy and immunofluorescence microscopy to characterize the structure of in vitro high shear thrombi. We show that the occlusive portion of the thrombus consists of a thick, transverse cable spanning the channel width. The cable is made of hundreds of parallel strings of platelets joined by yarns of VWF fibers identified by immunofluorescence microscopy. The elements composing the occlusive structure - cable, strings, yarns, and fibers, listed in hierarchical order - are oriented in the direction of tension to confer high breakage strength and stability to resist the upstream pressure. This structural hierarchy supports VWF as a potential new target for the prevention and lysis of occlusive arterial thrombi.