RetiredCapital BluecrossPolicy AHS - G2107

Measurement of Thromboxane Metabolites for ASA Resistance

This policy governs coverage for measurement of urinary thromboxane metabolites (e.g., AspirinWorks) to evaluate aspirin resistance for members of Capital BlueCross. It describes clinical background, coverage stance, coding, and related guidance that affect ordering and reimbursement.

Policy Summary

PayerCapital Bluecross

PolicyMeasurement of Thromboxane Metabolites for ASA Resistance

Policy CodePolicy AHS - G2107

Change TypeRetired

Effective Date

Next Review Date

Key ActionDo not order measurement of urinary thromboxane metabolites (e.g., AspirinWorks) to evaluate aspirin resistance because it does not meet coverage criteria and is subject to denial.

SourceLink

POLICY UPDATE CHANGES

Policy was retired (RETIRED 3/1/2025).

Not coveredCoverage stance

≤1500 pg/mgFDA cutoff

15–25%Estimated prevalence

82570,84431Procedure codes

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Determination

Not medically necessary / Not covered

Not covered when ALL of the following apply:

Urinary thromboxane metabolite testing: Measurement of thromboxane metabolites in urine (e.g., AspirinWorks) to evaluate aspirin resistancen/a

This testing does not meet coverage criteria due to lack of published scientific literature demonstrating it is required and beneficial for diagnosis or treatment.

Measurement of thromboxane metabolites in urine (for example, the AspirinWorks assay) to evaluate aspirin resistance is specifically excluded from coverage. The policy states that for all indications this testing does not meet coverage criteria due to insufficient published scientific literature demonstrating that the test is required and beneficial for diagnosis or treatment.

Laboratory-developed tests (LDTs) for aspirin effect or thromboxane metabolite measurement are regulated under CLIA as high-complexity tests and are not FDA-approved or -cleared. The policy notes that while LDTs lack FDA approval/clearance, FDA clearance or approval is not currently required for clinical use of these laboratory-developed assays.

In summary, measurement of urinary thromboxane metabolites (eg, AspirinWorks) to assess aspirin responsiveness is considered not medically necessary and does not meet coverage criteria for any indication in this policy because available published evidence does not demonstrate that the testing is required or provides clinical benefit.

Coding and Procedure Codes

Applicable CPT/HCPCS Procedure CodesCPT

82570	Creatinine; other source.
84431	Thromboxane metabolite(s), including thromboxane if performed, urine

Applicable CPT/HCPCS Procedure CodesCPT

82570	Creatinine; other source.
84431	Thromboxane metabolite(s), including thromboxane if performed, urine

FDA-established aspirin effect cutoff (11-dhTxB2/mg creatinine)

FDA-established cutoff (11-dhTxB2/mg creatinine)≤1500 pg 11-dhTxB2 per mg creatinine

Percent of non-aspirin users above cutoff88.2% (180/204) of samples from individuals not taking aspirin were above the cutoff

Aspirin users with lack of effect (81 mg/day)4.3% (7/163) of 81 mg/day aspirin users exceeded cutoff

Aspirin users with lack of effect (325 mg/day)10.5% (4/38) of 325 mg/day aspirin users exceeded cutoff

Overall aspirin users indicating lack of effect5.5% (11/201) of all aspirin users tested exceeded cutoff

Additional coding notes

Provider Actions, Billing, and Documentation

Billing Rule

Billing codes (reference)

Prior authorization is not specified for measurement of urinary thromboxane metabolites in this policy. billing/coding and prior authorization requirements may vary by contract — verify member-specific benefit coverage before ordering.

CPT 84431 — Thromboxane metabolite(s), urine (reference)
CPT 82570 — Creatinine; other source (reference)
Procedure codes are provided for reference and may not be all‑inclusive. Improper coding may lead to claim denials.

Note

Government policy override

If federal or state government coverage determinations (e.g., Medicare LCDs/NCDs or state Medicaid policies) conflict with this policy, the applicable government policy overrides and will be used to make coverage determinations.

Clinical Background

Aspirin exerts its antiplatelet effect by irreversibly inhibiting cyclooxygenase-1 (COX-1), which reduces platelet production of thromboxane A2 (TXA2), a potent promoter of platelet activation and aggregation. Failure of aspirin to suppress platelet TXA2 generation—often termed aspirin (ASA) resistance—has been reported in clinical studies, with some literature estimating a prevalence in affected populations. Urinary metabolites such as 11-dehydro-thromboxane B2 have been proposed as markers of systemic TXA2 generation and are the basis for assays like AspirinWorks; however, urine-based measures are not platelet-specific and the policy concludes there is insufficient evidence of clinical benefit to support coverage.

Definitions and Assay Descriptions

TXA2 / 11-dhTxB2 definition

Thromboxane A2 (TXA2)A platelet-activating prostanoid produced via the cyclooxygenase pathway that promotes platelet activation and aggregation

11-dehydro-thromboxane B2 (11-dhTxB2)A urinary metabolite proposed to indicate systemic TXA2 generation and used as a biomarker of thromboxane production

Clinical relevanceUrinary 11-dhTxB2 reflects systemic TXA2 generation but is not platelet-specific and may reflect extra-platelet sources

Aspirin (ASA) resistance definition

DefinitionAspirin (ASA) resistance is the inability of aspirin to decrease platelet production of thromboxane A2, leading to continued platelet activation and aggregation

Clinical implicationMay result in persistent platelet activation despite aspirin therapy

Policy Summary

PayerCapital Bluecross

PolicyMeasurement of Thromboxane Metabolites for ASA Resistance

Policy CodePolicy AHS - G2107

Change TypeRetired

Effective Date

Next Review Date

Key ActionDo not order measurement of urinary thromboxane metabolites (e.g., AspirinWorks) to evaluate aspirin resistance because it does not meet coverage criteria and is subject to denial.

SourceLink

On This Page

Additional coding notesNone listed in policy

Procedure codes referencedSee CPT codes 82570 and 84431 for urine creatinine and thromboxane metabolite testing

Coding disclaimerProcedure codes are provided as a general reference and may not be all-inclusive

Check CMS Medicare Coverage Database: https://www.cms.gov/medicare-coverage-database/search.aspx

Check applicable state Medicaid website for state-specific coverage rules.

Documentation Required

Provider actions when ordering/testing

Requests to measure urinary thromboxane metabolites (for example, AspirinWorks) do not meet coverage criteria per this policy and are subject to denial. Document the specific assay name and associated procedure code when submitting claims; include any supporting clinical rationale if pursuing an exception under member benefits.

Document the exact assay performed (e.g., AspirinWorks, VerifyNow-Aspirin, or laboratory-developed test) in the medical record and on the claim.
Include the specific CPT code (e.g., 84431) and any supporting documentation if an exception is requested.
Be aware LDTs may be used by labs; indicate if the test is an FDA-cleared assay or a laboratory-developed test (LDT).

Note

Provider actions — not otherwise specified

This section does not specify additional provider actions beyond billing/coding, government policy precedence, and the denial risk for urinary thromboxane metabolite testing. For any uncertain cases, confirm benefits and prior authorization requirements with the payer.

Verify member-specific coverage and prior authorization requirements before ordering.
When in doubt, contact the payer's provider services for guidance to avoid claim denials.

Prevalence noteReported prevalence varies by assay and population (policy notes estimates in other sections)

VerifyNow-Aspirin Assay — FDA 510(k) cleared

Assay nameVerifyNow-Aspirin Assay

FDA statusReceived 510(k) marketing clearance from the FDA in October 2004

Intended useQualitative assay to aid in detection of platelet dysfunction due to aspirin ingestion in citrated whole blood for point-of-care or laboratory settings

AspirinWorks — FDA 510(k) cleared

Assay nameAspirinWorks

FDA statusReceived 510(k) marketing clearance from the FDA in May 2007

Intended useIntended to aid in the qualitative detection of aspirin in apparently healthy individuals post ingestion

Laboratory-developed test (LDT) — CLIA regulation note

DefinitionLaboratory-developed test (LDT): a test developed and validated by a laboratory and regulated by CMS under CLIA '88 as high-complexity tests

FDA statusLDTs are not approved or cleared by the FDA; FDA clearance or approval is not currently required for clinical use

Regulatory oversightLDTs are regulated by the Centers for Medicare and Medicaid (CMS) under CLIA '88