What does the Aspirin (acetylsalicylic acid) Works test measure?

What Does the Aspirin Works Test Measure?

The Aspirin Works test measures platelet function to determine if a patient is responding adequately to aspirin therapy by assessing the degree of inhibition of the cyclooxygenase-1 (COX-1) enzyme pathway in platelets. 1

Mechanism of Aspirin and Need for Testing

Aspirin (acetylsalicylic acid) works by irreversibly inhibiting the platelet COX-1 enzyme, which prevents the formation of thromboxane A2, a potent vasoconstrictor and platelet aggregator. This inhibition reduces platelet aggregation and decreases the risk of thrombotic events 1.

However, approximately 10-20% of patients taking aspirin experience recurrent vascular events within 5 years despite treatment. Many of these patients may be "aspirin resistant" or only partially responsive to aspirin's antiplatelet effects 1.

Specific Platelet Function Tests for Aspirin Response

Several methods are available to measure aspirin's effectiveness:

1. Serum Thromboxane B2 Measurement:

   • Measures thromboxane B2 (stable metabolite of thromboxane A) in serum
   • Most directly evaluates aspirin's pharmacological target (COX-1)
   • Considered the most specific test for aspirin's effect 1, 2

2. Platelet Function Analyzer (PFA-100):

   • Uses whole blood under high shear stress
   • Measures time to occlusion of an aperture by platelet plug formation
   • Specifically sensitive to aspirin with collagen/epinephrine cartridge
   • Point-of-care testing capability 1, 3

3. VerifyNow Aspirin Assay:

   • Automated point-of-care test using whole blood
   • Measures platelet-induced aggregation with specific aspirin cartridges
   • Results reported in Aspirin Reaction Units (ARU)
   • Values ≥550 ARU suggest aspirin resistance 1, 4

4. Conventional Aggregometry:

   • Measures changes in light transmission in platelet-rich plasma
   • Uses arachidonic acid as activator to specifically assess aspirin effect
   • Considered a reference method but requires specialized laboratory 1

5. Urinary 11-dehydro-thromboxane B2:

   • Measures metabolite of thromboxane in urine
   • Represents an index of thromboxane biosynthesis in vivo
   • Can detect non-compliance but also sensitive to other cellular sources of thromboxane 2

Clinical Significance and Limitations

Despite the availability of these tests, current clinical guidelines do not support routine screening for aspirin resistance 1. Key limitations include:

• Lack of standardized normal ranges for many assays
• Different equipment measures different signals
• Influence of anticoagulants and agonists on test results
• Unclear relationship between test results and clinical outcomes 2

The reproducibility of these tests can be problematic. For example, the PFA-100 has shown coefficients of variation of 26.6% in patients on aspirin therapy, indicating significant variability in results 3.

Practical Considerations

When interpreting aspirin response test results, clinicians should consider:

• Patient compliance with therapy
• Drug interactions that may interfere with aspirin's effect
• Other mechanisms of platelet activation not affected by aspirin
• The possibility that the test may be identifying a generalized high platelet reactivity phenotype rather than specific aspirin resistance 4

The most appropriate use of these tests would be in high-risk patients with recurrent thrombotic events despite aspirin therapy, though even in these cases, the clinical decision-making based on test results remains challenging due to limited evidence connecting test results to outcomes.