Platelet deposition on von Willebrand factor-deficient vessels. Extracorporeal perfusion studies in swine with von Willebrand's disease using native and heparinized blood

Abstract

Native (nonanticoagulated) and heparinized blood from both normal swine and swine with von Willebrand's disease was exposed to de-endothelialized thoracic aorta from normal pigs under controlled flow conditions. We have shown that these normal de-endothelialized vessel segments do not contain von Willebrand factor (vWF) in the subendothelial surface; thus, the vascular model that we are using here is representative of the conditions in severe von Willebrand's disease. The blood was recirculated for selected periods of time through an extracorporeal circuit (carotid-jugular shunt), containing a tubular perfusion chamber that held the vessel segment. Flow rates and chamber diameters were selected such that the wall shear rates at the vascular segment were 212 to 3380 sec-1. Platelets were labeled with indium 111 and their total deposition determined by a gamma counter; selected areas were also observed by electron microscopy. When native blood was perfused, the deposition of platelets depended on platelet-plasma vWF only at high wall shear rates (1690 sec-1 or greater) typical of the microcirculation, but not at the lower shear rates (212 and 424 sec-1), more characteristic of the larger arteries and veins. In contrast, when heparinized blood was perfused, platelet deposition on the vascular segments depended on the presence of vWF over the entire range of shear conditions studied. These findings demonstrate in an extracorporeal perfusion system that the defect in platelet-vessel wall interaction in swine with von Willebrand's disease is influenced by both the local flow conditions and the level of activation of the coagulation system. In the presence of an intact coagulation system a synergistic interaction between procoagulant moieties and vWF was observed at high shear rates.