ANTITHROMBOTIC EFFECTS AND BLEEDING RISK OF AJVW-2, A MONOCLONAL-ANTIBODY AGAINST HUMAN VON-WILLEBRAND-FACTOR

1 A murine anti-human VWF monoclonal antibody, AJvW-2, was developed t hat inhibited the interaction between platelet glycoprotein Ib (GPIb) and von Willebrand factor (VWF) during the ristocetin-(IC50=0.7 +/- 0. 1 mu g ml(-1)) and botrocetin-(IC50=1.8 +/- 0.3 mu g ml(-1)) induced a ggregation of human platelets. 2 AJvW-2 inhibited the high shear stres s (10.8 N m(-2)) induced aggregation of human platelets dose-dependent ly with an IC50=2.4 +/- 0.3 mu g ml(-1), but had no effect on low shea r stress induced platelet aggregation (1.2 N m(-2)) up to 100 mu g ml( -1). 3 AJvW-2 also inhibited the high shear stress (5.0 N m(-2)) induc ed adhesion of human platelets to collagen I with the same efficacy (I C50=2.4 +/- 0.3 mu g ml(-1)), but had no effect at low shear condition s (1.5 N m(-2)). 4 AJvW-2 inhibited the botrocetin-induced aggregation of platelets from guinea-pig, rat, rabbit, dog and pig at the same co ncentration range as human platelets; it likewise also inhibited the h igh shear stress induced aggregation and adhesion to collagen I of gui nea-pig platelets. 5 AJvW-2 prevented arterial thrombus formation in g uinea-pigs at a dose of 100 mu g kg(-1) without prolonging the templat e bleeding time, whereas the GPIIb/IIIa antagonist lamifiban mediated inhibition of thrombosis at 1000 mu g kg(-1) was accompanied by a sign ificant prolongation of the bleeding time. 6 These results suggest tha t AJvW-2 is a potent inhibitor of the GPIb-vWF interaction and a poten tial novel antithrombotic agent with lower bleeding risk than GPIIb/II Ia antagonists.