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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2420.)
© 2004 American Heart Association, Inc.

Thrombosis

Increased Vascular Wall Thrombogenicity Combined With Reduced Blood Flow Promotes Occlusive Thrombus Formation in Rabbit Femoral Artery

Atsushi Yamashita; Eiji Furukoji; Kousuke Marutsuka; Kinta Hatakeyama; Hiroshi Yamamoto; Shozo Tamura; Yasuo Ikeda; Akinobu Sumiyoshi; Yujiro Asada

From First Department of Pathology (A.Y., K.M., K.H., A.S., Y.A.) and the Department of Radiology (E.F., S.T.), Miyazaki Medical College, University of Miyazaki, Miyazaki; Pharmaceutical Research Laboratories (H.Y.), Ajinomoto Co, Inc, Kawasaki; and the Department of Medicine (Hematology) (Y.I.), Keio University School of Medicine, Tokyo, Japan.

Correspondence to Yujiro Asada MD, PhD, First Department of Pathology, Miyazaki Medical College, Miyazaki University, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. E-mail yasada{at}fc.miyazaki-u.ac.jp

Objective— Plaque disruption does not always result in complete thrombotic occlusion. The mechanism of arterial thrombus propagation remains unclear.

Methods and 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.

We demonstrated in an animal model that increased vascular wall thrombogenicity combined with a blood flow reduction (>75%) promoted occlusive thrombus formation that was prevented by inhibiting plasma vWF. Reduced blood flow at plaque disruption sites might contribute to thrombus propagation and lead to acute coronary syndromes.

Key Words: thrombus propagation • blood flow • von Willebrand factor • tissue factor

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