The Role of Willebrand Factor in Platelet-Blood Vessel Interaction, Including a Discussion of Resistance to Atherosclerosis in Pigs with von Willebrand's Disease [and Discussion]

Von Willebrand pigs have all the manifestations of the severe human disease. The role of Willebrand antigen (VIII R:AG) and ristocetin cofactor (VIII:RWF) was assessed in these pigs by (1) transfusion and (2) `in vitro' bleeding time assay. The skin bleeding time became normal when the level of transfused Willebrand factor (VIII R:AG/RWF) was raised in the plasma above 30 U/dl. After single or repeated transfusions, skin capillary endothelium and platelets were still distinguished from normal by VIII R:AG deficiency. When incisions in excised porcine skin (`in vitro' bleeding time) were perfused with blood and plasma fractions, haemostasis occurred when plasmatic Willebrand factor exceeded 30 U/dl whether the skin or platelets came from normal or from von Willebrand pigs. The platelet plug occluding the skin incision contained VIII R:AG by immunofluorescence. Willebrand factor appears to coat surfaces and to serve as a platelet attachment protein. These bleeder pigs are resistant to atherosclerosis. If platelets are involved in early atheroscolerotic lesions, the role of Willebrand factor in platelet - blood vessel interaction may be important.