Pharmacological targeting of coagulation factors XII and XI by monoclonal antibodies reduces thrombosis in nitinol stents under flow.

BACKGROUND: Cardiovascular implantable devices, such as vascular stents, are critical to the treatment of cardiovascular diseases. However, their success is dependent on robust and often long-term antithrombotic therapies. Yet, the current standard-of-care therapies often pose significant bleeding risks to patients. Coagulation FXI and FXII has emerged as a potentially safe and efficacious target to safely reduce pathological thrombin generation in medical devices.

OBJECTIVE: To study the efficacy of monoclonal antibody targeting factors (F) XII and XI of the contact pathway in preventing vascular device-related thrombosis.

METHODS: The effects of inhibition of FXII and FXI using function-blocking monoclonal antibodies were examined in a non-human primate model of nitinol stent-related thrombosis under arterial and venous flow conditions.

RESULTS: We found that function-blocking antibodies of FXII and FXI reduced markers of stent-induced thrombosis in vitro and ex vivo. However, FXI inhibition resulted in more effective mitigation of thrombosis markers under varied flow conditions.

CONCLUSION: This work provides further support for the translation of contact pathway of coagulation inhibitors for their adjunctive clinical use with cardiovascular devices.