Prevention of acute venous stent-induced thrombosis using inhibition of fxii

Acute proximal lower extremity deep vein thrombosis (DVT) affects 1-2 per 1000 patients annually and confers significant acute and chronic morbidity and mortality. Pulmonary embolism (PE) and post-thrombotic syndrome (PTS) remain prevalent and hard-to-manage complications after DVT despite medical therapy. Treatment and recanalization of symptomatic, iliofemoral venous stenosis or obstruction, the long-term sequelae of DVT and DVT-associated PTS, by angioplasty and stenting is indicated in select ambulatory patients. While venous stenting can improve and restore blood flow in some cases, patency rates are poor with 1-year patency rates of 70% and significantly lower 5-year patency rates. After stenting, medical management of DVT requires either anti-platelet therapy and/or anticoagulation, which improves primary patency rates but carries a significant, 2-4% annual risk of major bleeding. Modern anticoagulation therapy including vitamin K antagonists, direct thrombin inhibitors and Factor X inhibitors have significant bleeding risks due to the impairment of hemostasis. As many patients require long-term medical therapy, development of a novel anticoagulant with a lower risk profile is critical. Since coagulation factor XII (FXII) supports contact activation of blood but has no known contribution to hemostasis, we sought to determine the thrombogenic role of FXII in an acute ex vivo venous stent model utilizing a FXII-neutralizing monoclonal antibody, 5C12.