Hot under the clot: venous thrombogenesis is an inflammatory process

Abstract

Venous thrombosis (VT) is a serious medical condition in which a blood clot forms in deep veins, often causing limb swelling and pain. Current anti-thrombotic therapies carry significant bleeding risks resulting from targeting essential coagulation factors. Recent advances in this field have revealed that the crosstalk between the innate immune system and coagulation cascade is a key driver of VT pathogenesis, offering new opportunities for potential therapeutic interventions without inducing bleeding complications. This review summarizes and discusses recent evidence from preclinical models on the role of inflammation in VT development. We highlight the major mechanisms by which endothelial cell activation, Weibel-Palade body release, hypoxia, reactive oxygen species, inflammasome, neutrophil extracellular traps, and other immune factors cooperate to initiate and propagate VT. We also review emerging clinical data describing anti-inflammatory approaches as adjuncts to anticoagulation in VT treatment. Finally, we identify key knowledge gaps and future directions that could maximize the benefit of anti-inflammatory therapies in VT. Identifying and targeting the inflammatory factors driving VT, either at the endothelial cell level or within the clot, may pave the way for new therapeutic possibilities for improving VT treatment and reducing thromboembolic complications without increasing bleeding risk.