6-ketoprostaglandin-f1-alpha and von-Willebrand-Diseases

The production of thomboxane B2, the primary metabolite of thromboxane A2, and 6-keto prostaglandin F1 alpha, the primary metabolite of prostacyclin, were measured in response to a standardized vascular injury, the bleeding time, in patients with von Willebrand's disease and in patients with platelet function defects. Compared to controls, thromboxane B2 levels in bleeding time blood were significantly lower in subjects with von Willebrand's disease. In patients with platelet function defects associated with a deficient response to thromboxane A2, thromboxane B2 production in bleeding time blood was similar to controls. In subjects with other platelet function defects, thromboxane production was significantly lower than normal. 6-keto PGF1 alpha production in bleeding time blood was not significantly different in patients compared to controls. The results suggest that bleeding time thromboxane production is influenced by the extent of platelet-vessel interaction.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Blood Platelet Disorders; Blood Platelets; Blood Vessels; Child; Child, Preschool; Humans; Middle Aged; Platelet Aggregation; Thromboxane B2; Thromboxanes; von Willebrand Diseases

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.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aorta, Thoracic; Blood; Blood Platelets; Blood Vessels; Disease Models, Animal; Endothelium; Epoprostenol; Fluorescent Antibody Technique; Heparin; Kinetics; Microscopy, Electron; Perfusion; Platelet Aggregation; Swine; von Willebrand Diseases; von Willebrand Factor