Abstract 5886: Novel Inhibition of Integrin α2bβ3 for Prevention of Venous Stent Thrombosis
Objective: The use of venous stents for the treatment of acute or chronic venous obstruction is increasing dramatically. Optimal thromboprophylaxis following venous stent deployment has not been defined. Study objective was to determine the efficacy of integrin α2bβ3 (GPIIbIIIa) inhibition for the prevention of venous compared to arterial thrombosis.
Methods: Pigs received either lamifiban (0.2 mg/kg bolus plus 0.2 mg/kg/hr infusion; n=6) or saline (n=12) prior to bilateral carotid crush injury. Thirty minutes later, thrombi were harvested. Iliac venous stents were then deployed and the thrombus was allowed to propagate for 2 hours before harvesting. Thrombus size was measured by scintillation detection of autologous 111In-platelets and by venous thrombus weights.
Results: Lamifiban completely inhibited in vitro platelet aggregation. Following arterial injury, platelet deposition (×106/cm2) was reduced by lamifiban (398±437) compared to saline control (1540±883; p<0.005). Lamifiban reduced venous thrombus platelet deposition (Figure A⇓), without preventing venous thrombosis (Figure B⇓). Four of six venous stents treated with lamifiban were grossly occluded. A correlation was noted between venous thrombus weights and platelet deposition for lamifiban pigs (Figure C⇓).
Conclusions: Platelet recruitment to venous stent thrombi occurs through the integrin α2bβ3 receptor. Although effective in preventing arterial thrombosis, inhibition of this pathway is not sufficient to prevent venous stent thrombosis. Aggressive inhibition of platelet adhesion may be essential to limit platelet deposition below the threshold necessary to support thrombin generation.