• Diagnose aspirin resistance

Low-dose aspirin therapy is prescribed to help prevent secondary, and sometimes primary, heart attack and stroke. It inhibits platelet aggregation primarily by blocking COX-1 enzymatic activity, thereby decreasing production of thromboxane A2, a platelet aggregation activator.

Clinical response to aspirin varies among individuals; approximately 10% to 20% of patients with atherothrombosis develop recurrent cardiovascular disease or stroke despite aspirin treatment.¹ This lack of aspirin responsiveness has been called “aspirin resistance.” Aspirin resistance has also been defined in terms of laboratory evidence of insufficient platelet inhibition. Neither the clinical nor the laboratory definition of aspirin resistance is precise or universally accepted. Patients may experience a vascular event in spite of optimal aspirin dosing or in vitro evidence of platelet inhibition.

Currently available tests include functional and biochemical methods. However, there is no standardized method for platelet function monitoring.² Functional assays include in vitro platelet aggregation, shear-induced platelet adhesion (eg, PFA-100), and platelet contribution to clot shear elasticity.³ Biochemical methods measure activation-dependent changes in the platelet surface or activation-dependent release of chemicals from platelets (eg, serum thromboxane B2 or urinary 11-dehydrothromboxane B2 [11-dhTxB2]).³

This test measures the level of 11-dhTxB2 in urine. 11-dhTxB2 is a stable metabolite of thromboxane A2. Elevated 11-dhTxB2 levels have been associated with an increased risk of stroke, heart attack, early saphenous vein graft thrombosis after coronary artery bypass graft surgery, and cardiovascular death.^1,4,5

• Individuals who had a recurrent thrombotic event despite aspirin therapy

• Individuals who have known coronary vascular disease

Avoid testing people with a urinary tract infection, severe liver disease, or end-stage renal disease.⁶

• Enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody targeting 11-dhTxB2

An 11-dhTxB2 urine level >1500 pg/mg creatinine should be expected in healthy, aspirin-free individuals. In patients receiving low-dose aspirin therapy, such levels suggest insufficient inhibition of the patient’s COX-1 pathway. The result is consistent with aspirin resistance, inadequate adherence to aspirin therapy, concomitant use of a nonsteroidal anti-inflammatory drug (ie, ibuprofen), genetic mutations in the COX-1 gene, non-platelet sources (eg, monocyte or macrophage) of thromboxane A2, and high platelet turnover.^5,7,8

A level ≤1500 pg/mg creatinine in individuals taking aspirin indicates complete inhibition of the COX-1 pathway. Such levels are consistent with response to aspirin therapy.