Aetiology

Virchow's triad (i.e., venous stasis, vessel wall damage, and hypercoagulability) remains the preferred aetiological model for deep vein thrombosis (DVT) and PE.[1]

  • Vessel wall damage: endothelial cell damage promotes thrombus formation, usually at the venous valves. Damage to the vessel wall can occur after a number of insults including trauma, previous DVT, surgery, venous harvest, and central venous catheterisation.[14]

  • Venous stasis: poor blood flow and stasis promote the formation of thrombi. Venous stasis and congestion result in valvular damage, further promoting thrombus formation. Increased venous stasis is associated with age >40 years, immobility, general anaesthesia, paralysis, spinal cord injury, myocardial infarction, prior stroke, varicose veins, advanced congestive heart failure, and advanced COPD.

  • Hypercoagulability: a number of other conditions (both inherited and acquired) increase the risk of PE. These include cancer, high-oestrogen states (oral contraceptives, hormone replacement, obesity, pregnancy), inflammatory bowel disease, nephrotic syndrome, sepsis, blood transfusion, and inherited thrombophilia (factor V Leiden mutation, prothrombin gene mutation, protein C and S deficiency, antithrombin deficiency, and antiphospholipid antibody syndrome).

Pathophysiology

Thrombi rarely develop de novo in the pulmonary vasculature. Clots usually form in the deep venous system of the lower extremities and embolise. The pathophysiology is therefore directly related to that of deep vein thrombosis (DVT). DVT in the upper extremities is associated with a lower incidence of PE.[15]

Endothelial damage appears to be less important in DVT than in arterial thrombosis.[16] Unlike platelet-rich arterial thrombi, DVTs are composed mainly of fibrin and entrapped erythrocytes (red clots). Although platelet aggregation is seen, it is not evident at the site of thrombus attachment, suggesting that activation of the coagulation cascade precedes platelet activation. [16][17]

PE occurs when a thrombus dislodges and becomes trapped in the pulmonary vasculature. This obstruction increases pulmonary vascular resistance (PVR), increasing the work of the right ventricle. The right ventricle compensates by increasing heart rate using the Frank-Starling preload reserve via dilation. Further increases in PVR overcome the right ventricular (RV) compensatory mechanisms, leading to over-distension of the right ventricle, increased RV end-diastolic pressure, and decreased RV cardiac output. Decreased RV output leads to decreased left ventricular (LV) preload. As left ventricle filling and cardiac output decrease, lowered mean arterial pressure progresses to hypotension and shock. In previously healthy individuals, this can occur when as little as 50% of the pulmonary vasculature is occluded.[18]

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