Urinary 11-Dehydrothromboxane B2 Levels in Healthy Individuals Following a Single Dose Response to Two Concentrations of Aspirin.

Introduction: The purpose of this protocol was to determine the effect of aspirin on urinary 11-dehydrothromboxane B₂ (11-DHT) levels in normal healthy adults who had ingested a single dose of aspirin (ASA).

Methods: We enrolled 50 normal healthy volunteers 18–58 years of age who had not ingested ASA or other NSAIDs for the previous 14 days. A baseline urine specimen was obtained followed by ingestion of a single 81 mg enteric-coated ASA. Twenty-four hours later a post-ASA urine specimen was obtained. Two weeks later another baseline urine specimen was obtained followed by a single 325 mg ASA enteric-coated tablet. Twenty-four hours later another post-ASA urine specimen was obtained. Urines were stored at -70°C until testing. Platelet response to aspirin was assessed using the 11-DHT immunoassay (Cayman Biochemical, Ann Arbor, MI). Aspirin Works® controls (Creative Clinical Concepts, Denver, CO) were utilized to control for lot to lot and run to run variability. Testing was completed by Hemostasis Reference Laboratories (Hamilton, ON). In 2002, HOPE study investigators computed quartiles by comparing clinical outcomes to urinary 11-DHT levels from subjects who were taking ASA to prevent a second adverse cardiovascular event. A level of 298 pg 11-DHT/mg urinary creatinine was the limit for determining platelet response to ASA and for projecting cardiovascular risk While 298 pg/mg was the lower limit of the fourth quartile, this limit may not apply to the 11-DHT effect of a single dose of ASA. Our limit for ASA response was established by determining the 50% difference between baseline and outcome. This approach was applied to both ASA concentration arms.

Results: Twenty-two of 48 subjects in the 81 mg ASA group showed an ASA response (46%). Forty of the 46 subjects (85%) in the 325 mg dosage group responded. The 325 mg ASA dose showed a significantly greater platelet response, based on mean 11-DHT levels.

Discussion: Previous studies have shown that non-responders to ASA have a greater risk of cardio-vascular problems using the quartile distribution. The current study may be used to extend these findings by applying them to single-dose ASA in normal healthy subjects. Further studies may apply these data to primary cardiovascular risk.