Asprin Dosing Estimator in Healthy Adults

AIM 1: Determine urine TXB2, platelet aggregation function testing (VerifyNow® ASA Test), salicylate level, CBC with differential, and hs-CRP, in 18 healthy volunteers across BMI classes of 22-25 (Normal Weight), >25-30 (Overweight), and > 30 kg/m2 (Obese).Total enrolled cohort: 60 patients and planned treatment cohort: 54 completed patients (anticipated dropout rate of 10% = 6 patients). The investigators have powered this sample size based on estimates of effect sizes from published studies examining platelet activation in patients across a range of BMIs and assuming an alpha = 0.05, with 80% power. In addition, height and weight as predictors will be evaluated independently of BMI. BMI patient groups (22-25, >25-30, and > 30 kg/m2) will be randomized to low-dose ASA (81mg standard-release), moderate dose ASA (325mg) or high dose ASA (500mg) (6 patients/each dose).

All patients will have a CBC with differential (to measure blood cell counts including platelets) and hs-CRP at baseline, serial urine TXB2 (-1, and 2 and 5 hours post ASA dose), platelet aggregation function testing using VerifyNow® ASA Test 15 min post ASA dose, serial salicylate levels (0, 15", 2 hours post-ASA dose) and again 10-14 days after chronic dosing (urine TXB2 2 hours post ASA dose and platelet aggregation function testing using VerifyNow® Test 15 min post ASA dose only).

AIM 2: Model associations between construct variables (BMI and aspirin dose) with predictive variables as collected in AIM 1. Multiple and Linear Regression with backward selection will be used. In addition, a Structured Equation Model will be applied to the data. Statistical assessment of model fit will be conducted for all models.

AIM 3: Build an Aspirin Dose Estimator to predict aspirin dosing. Model associations from AIM 2 will create demand estimates that will feed into a user-friendly aspirin dosage estimator. The simulator will comprise: 1) Entry: An entry screen. In this screen the user will enter the features of patient clinical information attributes. The user then clicks a 'run' button. 2) Demand Output: The simulator will then create an output screen that will show graphically aspirin dosing options.

Inclusion criteria

• Ages 18-55 years old (male or female)
• Healthy Volunteers (medication free without acute or chronic significant health problems or pathologies)

Exclusion criteria

• History of asthma
• History of chronic bronchitis
• History of emphysema
• History of renal impairment (eGFR < 30 ml/min)
• History of hypertension (reviewed by study staff)
• History of hyperlipidemia
• History of diabetes
• History of smoking (within last month)
• Current depression or anxiety requiring medication therapy
• Inability to finish the study for any reason
• Any current pathological condition outside of normal range
• Thrombocytopenia (platelet count < 150 K/µL)
• Other known platelet disorders (eg. von Willebrand disease, Glanzmann thrombasthenia, Bernard-Soulier Syndrome)
• Current use of dipyradamole, PGY 12 inhibitors, NSAIDs
• Or as otherwise determined by the investigative team