Abstract 717: Venous Stenting: Comparison of PD0348292, an oral Direct Factor Xa Inhibitor, and Anti-platelet Agents for the Inhibition of Venous Thrombosis in vivo
Background: The clinical use of venous stents for the treatment of acute or chronic venous obstruction is increasing dramatically. Although antiplatelet agents are required therapy for arterial stents, optimal thrombo-prophylaxis following venous stent placement has not been defined.
Methods: To determine whether an anticoagulant or an anti-platelet agent would most effectively prevent venous thrombosis, pigs received an oral direct factor Xa inhibitor, PD0348292 at 0.4, 0.9, or 4.3 mg/kg; PD0348292 (0.4 mg/kg) plus aspirin (325 mg); aspirin; clopidogrel (75mg), aspirin plus clopidogrel, or vehicle (n=6–10 per group). PD0348292 was given 4 hr prior to stent placement and aspirin and clopidogrel were given daily for 2 days prior to the placement of iliac venous stents. Following stent placement, the thrombus was allowed to propagate for 2 hours before harvesting. Thrombus size was measured by scintillation detection of autologous 111In-platelets and by weight.
Results: Factor Xa Inhibition with PD0348292 prolonged the prothrombin time 1.4 –2.9 fold in a dose dependent manner and effectively prevented venous thrombus formation. Thrombus weights and platelet deposition were significantly reduced for pigs receiving the oral direct factor Xa inhibitor PD0348292 at each dose (Table⇓) compared to vehicle. Despite bleeding time and platelet aggregometry inhibition, neither aspirin, clopidogrel, nor aspirin plus clopidogrel were effective.
Conclusions: At PT prolongation between 1.4 and 2.9, anticoagulant therapy with a specific factor Xa inhibitor, PD0348292, completely inhibited thrombosis following iliac venous stenting. Moreover, platelet accretion in these venous thrombi appears to involve mechanistic pathways distinct from either arachidonate metabolism or ADP receptor occupation.