Advances in understanding the molecular mechanisms of venous thrombosis.

Venous thromboembolism (VTE) represents a leading cause of global mortality, however, the determinants that contribute to thrombus development remain incompletely understood. In this review, we discuss the role of inherited abnormalities of blood coagulation in VTE pathogenesis. In addition, we also consider recent emerging data suggesting other molecular and cellular determinants may also contribute. Specifically, we describe the role played by the inflamed endothelium, and the dysregulated responses to inflammatory stimuli that create a platform for pathological clot formation. We review the accumulating evidence that blood cells, contact pathway factors and protein disulphide isomerases all play key roles in VTE development. Finally, we discuss new insights into the role of metabolites arising from commensal gut bacteria and their potential role in facilitating VTE. This overview provides an update on these state-of-the-art developments and the opportunities they provide for new antithrombotic therapies with enhanced efficacy and improved safety profiles.