Clinical meaning
Virchow's triad describes the three broad categories of factors that contribute to thrombus formation: (1) Endothelial injury/dysfunction — damage to the vascular endothelium exposes subendothelial collagen and tissue factor, initiating platelet adhesion (via vWF → GP Ib receptor) and the coagulation cascade (tissue factor → factor VII → extrinsic pathway). Causes: atherosclerosis, trauma, surgery, catheter insertion, endotoxins, cigarette smoke, hyperhomocysteinemia, vasculitis. The intact endothelium is normally anti-thrombotic — it produces nitric oxide (vasodilator and platelet inhibitor), prostacyclin (PGI₂ — platelet inhibitor), thrombomodulin (activates protein C anticoagulant pathway), tissue plasminogen activator (tPA — fibrinolysis), and heparan sulfate (binds antithrombin III). (2) Venous stasis — reduced blood flow allows activated clotting factors to accumulate locally rather than being diluted and cleared by the liver. Stasis also prevents mixing of activated factors with their natural inhibitors (antithrombin, protein C/S). Causes: immobilization, prolonged travel, post-surgical, heart failure (reduced CO), atrial fibrillation (stagnant blood in the appendage → LAA thrombus → stroke), pregnancy (uterine compression of IVC), obesity (venous compression), varicose veins. (3) Hypercoagulability — increased tendency for inappropriate clot formation. Inherited: Factor V Leiden (most common — activated protein C resistance; heterozygous 5-7× VTE risk, homozygous 80× risk), prothrombin G20210A mutation, protein C deficiency, protein S deficiency, antithrombin deficiency. Acquired: malignancy (Trousseau syndrome — cancer procoagulant, tissue factor expression), oral contraceptives/HRT (estrogen increases factor synthesis), pregnancy, antiphospholipid syndrome, heparin-induced thrombocytopenia, nephrotic syndrome (urinary loss of antithrombin), DIC.