Shear-induced platelet aggregation and its inhibition by antiplatelet agents in cerebral ischemia

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 cerebralischemia, and also studied the effects of various pharmacological agents on SIPAin vitro and ex vivo. Platelet aggregation was induced by high shear stress (lORdyne/cm²), which is dependent on von Willebrand factor and on glycoproteins lIb/lIla and lb. In vitro studies, SIPA was inhibited by agents that increase the activity of adenylate cyclase as well as inhibitors of platelet ionizedcalcium, 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 strokeand transient ischemic attacks, but not in those with lacunar stroke. SIPA was more oftenincreased in patients who showed an increase of larger von Willebrand factor multimers on SDS agarose gel electrophoresis. Oral aspirin did not inhibitSIPA, but oral ticlopidine significantly inhibited it. The above results indicate that SIPA is mediated or regulated by cyclic AMP, cytoplasmic calcium, and AD, and also indicate that SIPA is increased in some SUbtypes of cerebral ischemia, and can be corrected by ticlopidine but not by aspirin.