Affiliations: Department of Neurology, Tokyo Women's Medical College, Shinjuku-ku, Tokyo 162, Japan | Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160, Japan | Medical Devices and Diagnostics Research Laboratory, Toray Industries Inc., Otsu 520, Shiga, Japan
Abstract: Recent evidence suggests that shear-induced platelet aggregation (SIPA) is an important mechanism of thrombosis at arterial bifurcations or stenotic lesions. We measured SIPA using newly-developed equipment in patients with cerebral ischemia, and also studied the effects of various pharmacological agents on SIPA in vitro and ex vivo. Platelet aggregation was induced by high shear stress (108 dyne/cm2), which is dependent on von Willebrand factor and on glycoproteins IIb/ IIIa and Ib. In vitro studies, SIPA was inhibited by agents that increase the activity of adenylate cyclase as well as inhibitors of platelet ionized calcium, ADP receptor and Gj protein. but it was not affected by inhibitors of cyclooxygenase, lipoxygenase, thromboxane A2 synthetase, or platelet-activating factor. An increase of SIPA was observed in patients with atherothrombotic stroke and transient ischemic attacks, but not in those with lacunar stroke. SIPA was more often increased in patients who showed an increase of larger von Willebrand factor multimers on SDS agarose gel electrophoresis. Oral aspirin did not inhibit SIPA, but oral ticlopidine significantly inhibited it. The above results indicate that SIPA is mediated or regulated by cyclic AMP, cytoplasmic calcium, and ADP, and also indicate that SIPA is increased in some subtypes of cerebral ischemia, and can be corrected by ticlopidine but not by aspirin.
