ROLE OF PLASMA AND PLATELET VON-WILLEBRAND-FACTOR IN ARTERIAL THROMBOGENESIS AND HEMOSTASIS IN THE PIG

To evaluate the relative role of plasma and platelet von Willebrand fa ctor (vWF) pools in hemostasis and arterial thrombogenesis, pigs with vW disease (vWD) were injected with vWF concentrate and/or grafted wit h bone marrow from a normal pig. Hemostasis was assessed by measuremen t of ear immersion bleeding time, factor VIII (FVIII) activity, and pl asma and platelet vWF antigen levels. The thrombotic process was explo red at 650 s(-1) and 1600 s(-1) in an ex vivo cylindrical perfusion ch amber. Pigs with vWD exhibited a prolonged bleeding time (>30 minutes) compared with normal pigs (<5 minutes); in addition, they showed norm al platelet adhesion and thrombus formation at 650 s(-1) but profoundl y reduced platelet adhesion and thrombus formation at 1600 s(-1). Each experiment was performed before and 3 and 24 hours after injection of VWF concentrate. In our bleeding time study, only plasma VWF restorat ion induced a partial but delayed correction (24 hours postinjection), which was correlated with the highest measured level of FVIII activit y. In the perfusion chamber model, restoration of plasma or platelet v WE pools resulted in similar partial correction of platelet adhesion a nd average thrombus size. In the perfused pigs, the maximum correction occurred 3 hours postinjection. Platelet deposition reached normal va lues after vWF concentrate was injected into a grafted pig. The presen t results suggest that when both plasma and platelet vWF levels are re stored in vWD pigs, bleeding time and the thrombotic process are norma lized according to different kinetics and with differing degrees of ef fectiveness.