Critical role of von Willebrand factor and platelet interaction in venous thromboembolism
Misaki Takahashi1, Atsushi Yamashita1, Sayaka Moriguchi-Goto1, Kousuke Marutsuka1, Yuichiro Sato1, Hiroshi Yamamoto2, Chihiro Koshimoto3 and Yujiro Asada1
1Department of Pathology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan, 2Pharmaceutical Research Laboratories, Ajinomoto Co, Inc, Kawasaki, Japan and 3Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.
Offprint requests to: Yujiro Asada, M.D., Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. e-mail: yasada@fc.miyazaki-u.ac.jp
Summary. It has been generally considered that platelets are less important in venous thrombus formation. However, clinical studies have shown an association between venous thromboembolism (VTE) and von Willebrand factor (VWF). We therefore investigated the contribution of VWF and platelet interaction to the onset of VTE using tissues from autopsies and from an animal model. An immunohistochemical study revealed that glycoprotein (GP) IIb/IIIa, fibrin, glycophorin A (erythrocyte-specific protein) and VWF were consistently localized in ilio-femoral venous thrombi and in pulmonary thromboemboli from 8 autopsied cases who died of VTE, and VWF was closely associated with GPIIb/IIIa and fibrin. Venous thrombi and pulmonary emboli contained significant amounts of GPIIb/IIIa and VWF, in addition to glycophorin A and fibrin, and the factors did not significantly differ between them. A rabbit model of VTE was developed by inserting a polyethylene tube into the iliac vein. The constituents of the induced thrombi were quite similar to those of human VTE. An antibody against VWF (AJW200), which inhibits interactions between the VWF A1 domain and platelet GPIb, significantly reduced venous thrombus formation and pulmonary thromboembolism in the model. These results suggest that VWF A1-platelet GPIb interaction plays a significant role in venous thrombus formation. Histol Histopathol 24, 1391-1398 (2009)
Key words: Venous thromboembolism, Platelet, Fibrin, von Willebrand factor, Glycoprotein Ib
DOI: 10.14670/HH-24.1391