title: Anti-platelet effect of aspirin is substantially reduced after administration of heparin during carotid endarterectomy.
abstract: OBJECTIVE
  Aspirin therapy is usually continued throughout the perioperative period to reduce the risk for thromboembolic stroke and myocardial infarction after carotid endarterectomy (CEA). Aspirin irreversibly binds cyclooxygenase-1, thereby reducing platelet aggregation for the lifetime of each platelet. However, recent research from this unit has shown that aggregation in response to arachidonic acid increases significantly, but transiently, during CEA, which suggests that the anti-platelet effect of aspirin is temporarily reversed. The purpose of the current study was to determine when this phenomenon occurs and to identify the possible mechanisms involved.
  
  
  METHODS
  Platelet aggregation was measured in platelet-rich plasma from 41 patients undergoing CEA who were stabilized with 150 mg of aspirin daily. Blood was taken at 8 time points: before anesthesia, after anesthesia, before heparinization, 3 minutes after heparinization, 3 minutes after shunt insertion, 10 minutes after flow restoration, 4 hours postoperatively, and 24 hours postoperatively. Platelet aggregation was also measured at similar times in a group of 18 patients undergoing peripheral angioplasty without general anesthesia.
  
  
  RESULTS
  All patient platelets were effectively inhibited by aspirin at the start of the operation. There was a significant intraoperative increase in platelet response to arachidonic acid in both groups of patients, which occurred within 3 minutes of administration of unfractionated heparin. In the CEA group this resulted in a greater than 10-fold increase in mean aggregation, to 5 mmol/L of arachidonic acid (5 mmol/L), rising from 3.9% +/- 2.2% preoperatively to 45.1% +/- 29.3% after administration of heparin ( P <.0001). This increased aggregation persisted into the early postoperative period, but by 24 hours post operation aggregation had returned to near preoperative values. Aggregation in response to other platelet agonists (adenosine diphosphate, thrombin receptor agonist peptide) showed only a small increase at the same time, which could be accounted for by a parallel increase in the level of spontaneous aggregation.
  
  
  CONCLUSIONS
  Administration of heparin significantly increases platelet aggregation in response to arachidonic acid, despite adequate inhibition by aspirin administered preoperatively. This apparent reversal in anti-platelet activity persisted into the immediate early postoperative period, and could explain why a small proportion of patients are at increased risk for acute cardiovascular events after major vascular surgery, despite aspirin therapy.
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, England, UK.
authors.forename: Sally E
authors.initials: SE
authors.lastname: Webster
authors.forename: David A
authors.initials: DA
authors.lastname: Payne
authors.forename: Chris I
authors.initials: CI
authors.lastname: Jones
authors.forename: Paul D
authors.initials: PD
authors.lastname: Hayes
authors.forename: Peter R F
authors.initials: PR
authors.lastname: Bell
authors.forename: Alison H
authors.initials: AH
authors.lastname: Goodall
authors.forename: A Ross
authors.initials: AR
authors.lastname: Naylor
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016718:Arachidonic Acid / Q000502:physiology; D001241:Aspirin / Q000494:pharmacology*; D016893:Carotid Stenosis / Q000601:surgery; D004347:Drug Interactions; D016894:Endarterectomy, Carotid; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D016718:Arachidonic Acid; D006493:Heparin; D001241:Aspirin