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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:877-882.)
© 1999 American Heart Association, Inc.

Original Contributions

AJvW-2, an Anti-vWF Monoclonal Antibody, Inhibits Enhanced Platelet Aggregation Induced by High Shear Stress in Platelet-Rich Plasma From Patients With Acute Coronary Syndromes

Koji Eto; Takaaki Isshiki; Hiroshi Yamamoto; Satoshi Takeshita; Masahiko Ochiai; Naoyuki Yokoyama; Ryota Yoshimoto; Yasuo Ikeda; Tomohide Sato

From the Department of Medicine (Cardiology), Teikyo University School of Medicine, Tokyo (K.E., T.I., S.T., M.O., N.Y., T.S.); the Central Research Laboratories, Ajinomoto Co, Inc, Yokohama (H.Y., R.Y.); and the Department of Medicine (Hematology), Keio University School of Medicine, Tokyo (Y.I.), Japan.

Correspondence to Koji Eto, MD, Department of Medicine (Cardiology), Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173, Japan. E-mail keto{at}med.teikyo-u.ac.jp

Abstract—The platelet aggregation that is dependent on von Willebrand factor (vWF) is important in the thrombogenesis that occurs under conditions of high shear stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody, AJvW-2, directed against the A1 domain of human vWF specifically blocks the interaction between plasma vWF and platelet glycoprotein (GP) Ib. To evaluate the association between the vWF-GPIb interaction and the enhanced shear-induced platelet aggregation (SIPA) observed in ACSs, we tested the effect of this antibody on platelet aggregation. Platelet-rich plasma was prepared from the citrated blood of 12 patients with unstable angina (UAP) and 20 patients with acute myocardial infarction (AMI) who were admitted within 3 hours of the onset of cardiac symptoms and from 18 controls. We observed the following: (1) 1.7-fold higher plasma levels of vWF and ristocetin cofactor activity in UAP patients and (2) 2.8-fold higher levels in the AMI group than in controls. Using a cone-and-plate viscometer, we measured the mean value of SIPA under high-shear conditions (108 dyne/cm²) and found them to be 1.3-fold higher in the UAP group and 2.0-fold higher in the AMI group than in controls. The high SIPA in all groups was completely inhibited by 10 µg/mL AJvW-2. Under low-shear conditions (12 dyne/cm²), platelet aggregation was increased only in the AMI group, but this was unaffected by AJvW-2. We observed a significant correlation in both ACS groups between high SIPA and the plasma vWF level or vWF larger multimers. These findings suggest that the vWF-GPIb interaction is important in coronary occlusion and that inhibition of this interaction (with the use of AJvW-2) may prevent further events in the coronary arteries.

Key Words: platelet aggregation • shear stress • glycoprotein Ib • von Willebrand factor • acute coronary syndromes

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