Pathophysiology
Clinical meaning
Venous thromboembolism (VTE) encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), representing a spectrum of the same pathological process. Thrombus formation in the venous system is governed by Virchow's triad: venous stasis, endothelial injury, and hypercoagulability. At the molecular level, venous stasis in valve pockets of deep veins creates a hypoxic microenvironment. Endothelial cells respond to hypoxia by upregulating P-selectin (stored in Weibel-Palade bodies) and expressing tissue factor on their surface. P-selectin recruits monocytes and neutrophils, which release tissue factor-bearing microparticles. Tissue factor activates Factor VII, initiating the extrinsic coagulation cascade and generating thrombin. Thrombin converts fibrinogen to fibrin, activates Factor XIII for cross-linking, and activates platelets via PAR-1 and PAR-4 receptors. Simultaneously, stasis impairs the natural anticoagulant mechanisms. Normally, flowing blood dilutes activated clotting factors and delivers antithrombin III to neutralize them. Thrombomodulin on intact endothelium binds thrombin, converting it from a procoagulant to an activator of Protein C (which inactivates Factors Va and VIIIa). Stasis disrupts all these protective mechanisms. Low-molecular-weight heparins (LMWHs) like enoxaparin exert their anticoagulant effect by binding to antithrombin III via a specific...