P-selectin antagonism causes dose-dependent venous thrombosis inhibition

Thromb Haemost. 2001 Mar;85(3):423-9.

Abstract

Inhibition of P-selectin by antibody or selectin antagonist decreases inflammation and thrombosis. This study evaluates the dose-response relationship using a selectin receptor antagonist. Eight male baboons (Papio anubis) underwent inferior vena caval thrombosis using a 6 h balloon occlusion model. Three animals received 500 microg/kg P-selectin antagonist (rPSGL-Ig) and five 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 saline controls and 8 animals that received 4 mg/kg rPSGL-Ig. A statistically significant dose-response relationship existed between rPSGL-Ig dose and thrombosis (p < 0.01), and between rPSGL-Ig dose and spontaneous recanalization (p<0.05). Inflammatory assessment revealed decreased gadolinium enhancement in all rPSGL-Ig groups compared to previously reported control, despite no significant differences in inflammatory cell extravasation. No dose of rPSGL-Ig caused anticoagulation. Selectin antagonism results in a dose-dependent decrease in thrombosis and increase in spontaneous recanalization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticoagulants / administration & dosage
  • Balloon Occlusion
  • Dalteparin / administration & dosage
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Antagonism
  • Drug Therapy, Combination
  • Inflammation / drug therapy
  • Male
  • Membrane Glycoproteins / administration & dosage*
  • P-Selectin / drug effects*
  • Papio
  • Venous Thrombosis / drug therapy
  • Venous Thrombosis / prevention & control*

Substances

  • Anticoagulants
  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Dalteparin