Aspirin in Pulmonary Embolism Prevention

Platelet activation and aggregation are not considered among the prime causes of venous thrombosis and pulmonary embolism, yet Colin Prentice, Professor of Medicine, the University of Leeds, reported that aspirin reduces them.

He proposed that aspirin works in venous thrombosis and embolism by inhibiting platelet activation so that the surface platelet phospholipids, which enhance thrombin formation, are not exposed.

He described the pulmonary embolism prevention trial (PEP), a study of thrombotic complications after hip fracture in 140 centres3. PEP randomised 13,356 patients undergoing surgery for fractured hip to daily aspirin 162 mg or placebo for 5 weeks. The surgeons could add heparin or other anticoagulation as they wished. The primary endpoints were mortality from fatal pulmonary embolism and cardiovascular diseases. Other endpoints were morbidity during hospital stay from pulmonary embolism, deep vein thrombosis and cardiovascular diseases, and total mortality at 5 weeks.

The patients ranged in age from 65 to 101. After 35 days 82 per cent were discharged from hospital and alive: 11 per cent were still in hospital, and 7 per cent had died. Pulmonary embolism was a relatively small proportion of total mortality (52 patients, 6%). In the aspirin group deaths from pulmonary embolism were half those in the placebo group. Non-fatal pulmonary emboli and deep vein thromboses were reduced by a third in the aspirin group, the main reduction in thromboses being in the femoral and iliac veins (p=0.0006). Adding heparin to aspirin made no difference to thromboembolism.

aspirin had no effect on local bleeding, such as haematomas. Wound bleeding was graded by blood transfusion: there was a very small difference in transfusion volumes. All the serious bleeds (6 per thousand) were easily treated by transfusion. Professor Prentice regards these data as substantiating the use of aspirin as an antithrombotic after hip surgery. It may cause less bleeding than heparin, the treatment is easily continued post-discharge, and is inexpensive.

Box 4. aspirin has a reputation for working in arterial but not venous thrombosis. The Pulmonary Embolism Prevention (PEP) trial showed that in patients with hip fractures treated surgically, it reduced deaths from pulmonary embolism by half. It caused no serious or unmanageable bleeding. PEP also showed that with modern surgery, deep vein thrombosis and pulmonary embolism are now very rare