Validation of an Assay to Measure Cyclooxygenase-1 Activity

Aspirin has been shown to reduce cardiovascular events in at-risk individuals, but some aspirin-treated patients fail to exhibit expected changes in bleeding time and platelet aggregation. Recent evidence has correlated aspirin "non-response" to poor cardiovascular outcomes.

In order to study the mechanisms of aspirin resistance, an assay is needed to measure the catalytic activity of platelet cyclooxygenase (which should be inhibited by aspirin). A common assay in general use is the measurement of thromboxane B2 production in clotting whole blood. This measure, however, is influenced by genetic and environmental variations in the glass-activated coagulation pathway, albumin binding capacity, platelet activation pathways, arachidonic acid pools, and phospholipase activity.

Our laboratory has developed a direct assay of platelet cyclooxygenase (COX-1) activity that is not influenced by these variations. This study will generate a reference range in normal volunteers taking a routine clinical dose of aspirin (81mg daily) for this assay.

Inclusion criteria

• Non-smoker
• No chronic medical illness
• No chronic medications

Exclusion criteria

• Aspirin/NSAID use in preceding 14 days
• History of chronic NSAID use
• Currently taking NSAIDs, opioid analgesics, corticosteroids, or anticoagulants
• History of coronary artery disease, myocardial infarction, coronary artery bypass grafting, percutaneous angioplasty, diabetes mellitus, or stroke.
• History of hypertension
• Body mass index > 35
• History of gastric, duodenal, or esophageal ulcers or serious gastrointestinal bleed
• History of frequent headaches, pain syndrome, or other condition requiring frequent use of analgesics
• History of adverse reactions to aspirin
• Screening platelet count < 100,000/ul or > 500,000/ul
• Screening hematocrit < 35% or > 50%
• Weight less than 110 pounds
• Pregnant females