Potential Role of Contact Pathway Factors in Catheter-Related Thrombosis: Emerging Evidence and Therapeutic Strategies.

The catheter is among the most commonly used blood-contacting medical devices, but its use can induce surface-mediated coagulation activation, leading to catheter-related thrombosis (CRT). The occurrence of CRT causes venous thromboembolism and catheter malfunction, but current antithrombotic strategies have unsatisfactory efficacy and safety profiles. Here, we review recent advances in the understanding of the pathology of CRT, particularly the roles of the contact pathway factors, and promising novel therapeutic options. Recent studies using genetically modified animals, factor-deficient plasmas, specific inhibitors and purified systems demonstrated an important contribution of contact pathway factors XII and XI to catheter-related blood clotting. Accordingly, contact pathway inhibition has efficacy comparable to that of heparins in mitigating catheter-related coagulation or intraluminal occlusion in various in vitro and animal models, while having lower bleeding risk. Early human studies suggest potential thromboprotective effects of FXI inhibition in catheter placement and hemodialysis settings. However, inhibition of factors XII or XI may impair the defense against infection or disturb normal cardiac function, respectively. Larger human trials are needed to further confirm the efficacy and safety of these contact pathway inhibitors, and to explore whether low-dose combinations of contact pathway inhibitors with heparins are more effective for CRT protection.