Post Doctoral Fellow FDA Silver Spring, Maryland, United States
Background: Shear-Induced Platelet Aggregation (SIPA) can form quickly and grow to occlusive thrombi to stop blood flow under arterial hemodynamic conditions. The structure of SIPA clot may contain valuable information on mechanism of formation and a way to treat arterial occlusions. However, it is hard to collect a structurally intact SIPA clot clinically.
Aims: Create large SIPA clot to study its structure via histology.
Methods: Macroscopic thrombi are made from porcine whole blood in a collagen-coated, large-scale, glass stenosis with high shear flow conditions of an atherosclerotic artery. The millimeter-sized thrombi are harvested for histology and scanning electron microscopy.
Results: Histological images showed 3 distinctive regions of thrombus architecture. 1) String-like platelet aggregates extend from the wall in stripes alternating with free RBCs upstream of the throat. The strings were >10x as long as they were wide and reached out to join the strings from the opposite wall. B) Near the apex, the thrombus was a dense mass with microchannels that effectively occludes the lumen. C) In the downstream expansion region, the thrombus occupied the centerline as a cone with an annulus of free blood in the flow separation zone. A thin shell of platelets at the wall of the expansion, separate from the core. The total clot is estimated to contain 1.23 billion platelets with pores on the order of 10-100 microns.
Conclusion(s): The histology reveals a complex structure of arterial thrombi that grow from their tips under high shear stress with VWF-platelet strings. The occluding thrombus is dominant at the apex and contains many microchannels that allow some mass transport through the bulk of the thrombus. This architecture can create occlusion or hemostasis rapidly with minimal platelet material, yet remain porous for potential delivery of lytic agents to the core of the thrombus.
