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

The platelet aggregation that is dependent on von Willebrand factor (vWF) i s important in the thrombogenesis that occurs under conditions of high shea r stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody , AJvW-2, directed against the Al domain of human vWF specifically blocks t he interaction between plasma vWF and platelet glycoprotein (GP) Ib. To eva luate the association between the vWF-GPIb interaction and the enhanced she ar-induced platelet aggregation (SIPA) observed in ACSs, we tested the effe ct of this antibody on platelet aggregation. Platelet-rich plasma was prepa red from the citrated blood of 12 patients with unstable angina (UAP) and 2 0 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 cofa ctor activity in UAP patients and (2) 2.8-fold higher levels in the AMI gro up than in controls. Using a cone-and-plate viscometer, we measured the mea n value of SIPA under high-shear conditions (108 dyne/cm(2)) and found them to be 1.3-fold higher in the UAP group and 2.0-fold higher in the AMI grou p than in controls. The high SIPA in all groups was completely inhibited by 10 mu g/mL AJvW-2. Under low-shear conditions (12 dyne/cm(2)), platelet ag gregation was increased only in the AMI group, but this was unaffected by A JvW-2. We observed a significant correlation in both ACS groups between hig h SIPA and the plasma VWF level or vWF larger multimers. These findings sug gest that the vWF-GPIb interaction is important in coronary occlusion and t hat inhibition of this interaction (with the use of AJvW-2) may prevent fur ther events in the coronary arteries.