L10: Haemostasis 5 – Thrombosis 1

A thrombus is a solid mass formed from blood constituents within the cardiovascular system during life. It is distinguished from post-mortem clot by its attachment to the vessel wall, its laminated (lines of Zahn) structure, and its composition. An embolus is a detached intravascular mass—thrombus, fat, air, amniotic fluid, or tumour—that travels in the bloodstream to lodge in a distant vessel, causing ischaemia or infarction.

Virchow's triad describes the three conditions predisposing to thrombosis: (1) endothelial injury, (2) abnormal blood flow (stasis or turbulence), and (3) hypercoagulability. Arterial and venous thrombosis differ in their predominant predisposing factors, composition, and clinical consequences.

Arterial thrombosis is predominantly driven by endothelial injury, most commonly from atherosclerotic plaque rupture. Disruption of a vulnerable plaque exposes subendothelial collagen and TF, triggering platelet adhesion, activation, and the coagulation cascade. Arterial thrombi are rich in platelets and fibrin (white thrombi), forming under conditions of high shear. They cause ischaemic stroke and myocardial infarction.

Venous thrombosis (deep vein thrombosis, DVT) is predominantly driven by stasis. Stagnant blood in valve pockets of leg veins becomes hypoxic; hypoxia activates endothelial cells to express selectins, which capture neutrophils. Activated neutrophils release neutrophil extracellular traps (NETs)—chromatin and granule proteins—that activate the contact pathway and provide a scaffold for coagulation. Tissue factor expression is also upregulated in hypoxic endothelium. Venous thrombi are fibrin-rich (red thrombi), forming under low-flow conditions.

DVT typically arises in the deep veins of the calf and may propagate proximally. The Wells Score quantifies pre-test probability of DVT by allocating points for clinical features (active cancer, immobility, calf swelling, pitting oedema, collateral veins, prior DVT, entire leg swelling, tenderness along deep venous system, paralysis or recent cast) and subtracting points if an alternative diagnosis is at least as likely. D-dimer testing has high sensitivity but low specificity; a negative result in low-probability patients effectively excludes DVT. Compression ultrasound demonstrating a non-compressible vein confirms DVT.

Untreated proximal DVT may embolise to the pulmonary circulation, causing pulmonary embolism (PE), with haemodynamic compromise and potentially death. Chronic venous insufficiency (post-phlebitic syndrome) results from damage to venous valves and vessel walls: patients develop varicose veins, chronic leg oedema, skin induration, and venous ulcers.

Heritable thrombophilia refers to genetic conditions predisposing to venous thrombosis. The most common are factor V Leiden (FVL; a point mutation Arg506Gln making FVa resistant to cleavage by Protein C, accounting for ~20% of VTE), prothrombin G20210A mutation, and inherited deficiencies of antithrombin, Protein C, or Protein S. Antiphospholipid syndrome (APS) is an acquired thrombophilia caused by autoantibodies (lupus anticoagulant, anticardiolipin, anti-β2GPI) that activate coagulation and endothelium.