Asprin's effectiveness decreases during carotid endarterectomy

Carotid Endarterectomy (CEA) is a well-established operation which reduces the risk of stroke in patients with atherosclerotic stenosis of the internal carotid artery. Paradoxically, the operation itself carries a risk of peri-operative stroke. This thesis comprises four sections: 1. Intravenous Dextran 40 solution has been shown to reduce the risk of post-operative stroke in patients with high numbers of post-operative emboli. It was hypothesised that Dextran applied locally to the operative field would be as effective as preventing emboli, but have a lower incidence of systemic complications. A randomised trial was carried out comparing Dextran 40 irrigation with conventional Heparinised Saline solution. Post-operative emboli were quantified and compared. 2. Previous work on platelet function during CEA showed an incidental significant increase in aggregation in response to arachidonic acid (the substrate for the Cyclo-oxygenase (COX) pathway) by the end of the operation. Aggregometry performed during CEA showed that the anti-platelet effect of aspirin was significantly reduced during and after surgery. This effect occurred within three minutes of the administration of intravenous unfractionated heparin (UFH) and had never previously been described. It contradicted all knowledge of aspirin's mechanism of action (irreversible acetylation of the Ser-529 residue of COX). 3. Further in vitro, ex vivo and ELISA studies were performed to determine the mechanisms behind the changes in platelet aggregation. 4. Evidence suggests that Low Molecular Weight Heparin (LMWH) causes less platelet activation than UFH. The final part of this thesis describes a pilot randomised trial comparing the effects of LMWH and UFH on the anti-platelet effect of aspirin. This reduction in aspirin's efficacy may be important, not just for patients undergoing CEA, but also may contribute to risk of thrombo-embolic complications in patients undergoing other vascular interventional procedures (surgery, angioplasty, stenting).