Increased vascular wall thrombogenicity combined with reduced blood flow promotes occlusive thrombus formation in rabbit femoral artery.
OBJECTIVE
Plaque disruption does not always result in complete thrombotic occlusion. The mechanism of arterial thrombus propagation remains unclear.


RESULTS
We studied how vascular wall thrombogenicity and blood flow reduction affect thrombus propagation using a rabbit model of single and repeated balloon injury. After balloon injury of the normal femoral artery, the blood flow was reduced to 50%, 25%, or 10% (n=5). Small mural thrombi composed of aggregated platelets were produced, but no occlusive thrombi developed in any flow reduction. Three weeks after the first balloon injury, neointima with tissue factor expression and increased procoagulant activity was developed. Balloon injury of the neointima with the same blood flow reduction (n=5) induced fibrin-rich thrombus formation. Additionally, injury with flow reduced to 25% and 10% promoted thrombus propagation resulting in vessel occlusion within 160+/-18 and 71+/-17 seconds, respectively. An injection of anti-von Willebrand factor (vWF) monoclonal antibody (AJW200; 1.0 mg/kg) prevented occlusive thrombus formation.


CONCLUSIONS
Increased vascular wall thrombogenicity together with a substantial blood flow reduction is crucial for occlusive thrombus formation, and vWF plays an important role in thrombus propagation. Reduced blood flow at plaque disruption sites might contribute to thrombus propagation leading to acute coronary syndromes.
First Department of Pathology, Miyazaki Medical College, Miyazaki University, Kiyotake, Miyazaki, Japan.
Atsushi
A
Yamashita
Eiji
E
Furukoji
Kousuke
K
Marutsuka
Kinta
K
Hatakeyama
Hiroshi
H
Yamamoto
Shozo
S
Tamura
Yasuo
Y
Ikeda
Akinobu
A
Sumiyoshi
Yujiro
Y
Asada
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology*; D002404:Catheterization / Q000009:adverse effects; D003238:Connective Tissue / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D003251:Constriction, Pathologic / Q000150:complications / Q000473:pathology; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000737:chemistry / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009389:Neovascularization, Pathologic / Q000150:complications / Q000473:pathology; D011817:Rabbits; D012039:Regional Blood Flow / Q000502:physiology*; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000150:complications* / Q000473:pathology*; D017539:Tunica Intima / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure
D013925:Thromboplastin