P-selectin antagonism causes dose-dependent venous thrombosis inhibition

Inhibition of P-selectin by antibody or selectin antagonist;decreases infla mmation and thrombosis. This study evaluates the dose-response relationship using a selectin receptor antagonist. Eight male baboons (Papio anubis) un derwent inferior vena caval thrombosis using a 6 h balloon occlusion model. Three animals received 500 mug/kg P-selectin antagonist (rPSGL-Ig) and fiv e 1 mg/kg rPSGL-Ig with or without a non-anticoagulant dose of Dalteparin. These animals were compared to our published results in this model with 4 s aline controls and 8 animals that received 4 mg/kg rPSGL-Ig. A statisticall y significant dose-response relationship existed between rPSGL-Ig dose and thrombosis (p < 0.01), and between rPSGL-Ig dose and spontaneous recanaliza tion (p<0.05). Inflammatory assessment revealed decreased gadolinium enhanc ement in all rPSGL-Ig groups compared to previously reported control, despi te no significant differences in inflammatory cell extravasation. No dose o f rPSGL-Ig caused anticoagulation. Selectin antagonism results in a dose-de pendent decrease in thrombosis and increase in spontaneous recanalization.