title: 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.
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 microgram/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.
authors: Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan. keto@med.teikyo-u.ac.jp
authors: K
authors: K
authors: Eto
authors: T
authors: T
authors: Isshiki
authors: H
authors: H
authors: Yamamoto
authors: S
authors: S
authors: Takeshita
authors: M
authors: M
authors: Ochiai
authors: N
authors: N
authors: Yokoyama
authors: R
authors: R
authors: Yoshimoto
authors: Y
authors: Y
authors: Ikeda
authors: T
authors: T
authors: Sato
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000789:Angina, Unstable / Q000097:blood; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood*; D005260:Female; D018056:Hemorheology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D010974:Platelet Aggregation / Q000276:immunology*; D013314:Stress, Mechanical; D013577:Syndrome; D014841:von Willebrand Factor / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D014841:von Willebrand Factor