Pathophysiology Thrombus formation and propagation depend on the presence of abnormalities of blood flow, blood vessel wall, and blood clotting components, known collectively as Virchow's triad. Abnormalities of blood flow or venous stasis normally occur after prolonged immobility or confinement to bed. Venous obstruction can arise from external compression by enlarged lymph nodes, bulky tumours, or intravascular compression by previous thromboses. Increased oestrogens at pharmacological levels, as seen with oral contraceptive use and with hormone replacement therapy in postmenopausal women, have been associated with a threefold increased risk in the small initial risk of venous thromboembolism. Cancers, particularly adenocarcinomas and metastatic cancers, are also associated with increased venous thromboembolism. Indeed, on presentation, some idiopathic venous thromboembolisms have revealed occult cancers at follow up. Both oestrogens at pharmacological levels and cancer can also activate the clotting system. Risk factors and conditions predisposing to venous thromboembolism History of venous thromboembolism Prolonged immobility Prolonged confinement to bed or lower limb paralysis Surgery, particularly lower limb orthopaedic operations, and major pelvic or abdominal operations Trauma—For example, hip fractures and acute spinal injury Obesity Major medical illnesses such as acute myocardial infarction, ischaemic stroke, congestive cardiac failure, acute respiratory failure Oestrogen use in pharmacological doses—For example, oral contraception pills, hormone replacement therapy Cancer, especially metastatic adenocarcinomas Age >40 years Aquired hypercoagulable states—Lupus anticoagulant and antiphospholipid antibodies, hyperhomocysteinaemia, dysfibrinogenaemia, myeloproliferative disorders such as polycythaemia rubra vera Inherited hypercoaguable states—Activated protein C resistance (factor V Leiden mutation), protein C deficiency, protein S deficiency, antithrombin deficiency, prothrombin gene mutation