Factor VIII beyond haemophilia: a hidden regulator of venous thrombosis and endothelial dysfunction.

Factor VIII (FVIII), a critical cofactor protein traditionally acknowledged for its deficiency in haemophilia A (HA), has been attracting interest for its substantial role in vascular disease. Recent data highlights its essential role beyond haemostasis, in the development of venous thrombosis (VT) and endothelial dysfunction influenced by genetic and acquired factors. This review summarizes the biology, synthesis, and activation of FVIII, emphasizing its role in thrombin generation and endothelial dysfunction. FVIII is implicated in inflammatory and thrombotic disorders, such as COVID-19, sepsis, and cancer-associated thrombosis. Although anticoagulant medication indirectly reduces elevated FVIII levels, direct intervention is constrained by the associated bleeding risks. Novel approaches like RNA interference, gene editing, and endothelial-specific modulation might offer compelling opportunities for the regulation of FVIII. This study highlights the potential of FVIII as a diagnostic and therapeutic target in thrombosis by integrating molecular insights with clinical data, hence promoting future precision-based therapies.