CurrentBlue Cross Blue Shield - TennesseePolicy N/A

Measurement of Thromboxane Metabolites for ASA Resistance

This policy governs coverage for tests that measure thromboxane metabolites in urine (e.g., AspirinWorks) to evaluate aspirin (ASA) resistance for Blue Cross Blue Shield - Tennessee members. It applies to providers requesting coverage for these assays under the payer's medical policy.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyMeasurement of Thromboxane Metabolites for ASA Resistance

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

Key ActionDo not request coverage or prior authorization for urinary thromboxane metabolite testing (AspirinWorks) to evaluate aspirin resistance because it does not meet coverage criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Not coveredcoverage stance

≤1500 pg/mgaspirin effect cutoff

15–25%estimated prevalence

30%+non-platelet contribution

2FDA-cleared assays

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Coverage Criteria

inv-01: Not Medically Necessary / Not Covered

Not covered

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

Does not meet coverage criteria due to lack of available published scientific literature confirming clinical benefit

All indications for measurement of urinary thromboxane metabolites (for example, the AspirinWorks assay) to evaluate aspirin resistance are excluded from coverage. The policy explicitly states that measurement of these urinary metabolites for any indication does not meet coverage criteria because of insufficient published scientific evidence that the tests are required and beneficial for diagnosis or treatment.

Measurement of thromboxane metabolites in urine (e.g., AspirinWorks) to assess aspirin resistance does not meet coverage criteria and is considered not medically necessary for the purposes of this policy.

inv-21: Detection of aspirin effect or ingestion using FDA-cleared assays (VerifyNow-Aspirin, AspirinWorks) or validated laboratory methods — covered indications logic

Covered when ALL of the following are met:

FDA-cleared assays or validated laboratory methods: Testing is performed using an FDA 510(k)-cleared assay (e.g., VerifyNow-Aspirin or AspirinWorks) or a laboratory-validated method

VerifyNow-Aspirin is a qualitative assay for detection of platelet dysfunction due to aspirin in citrated whole blood; AspirinWorks is intended to aid qualitative detection of aspirin post-ingestion

Coding and Procedure Codes

Applicable CPT/HCPCS Procedure CodesCPT

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

Aspirin effect cutoff (urinary 11dhTxB2)

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

Supporting dataFDA analysis: 88.2% of non-aspirin users above cutoff; 5.5% of aspirin users indicated lack of aspirin effect using cutoff

Unitspicograms (pg) 11dhTxB2 per milligram (mg) creatinine

Provider Actions and Billing Notes

Prior Authorization

Prior Authorization Required

Prior authorization is required for the listed procedure codes for this test. Providers must obtain prior authorization through Blue Cross Blue Shield of Tennessee’s established prior authorization process before performing or billing for testing under CPT codes 82570 and 84431.

Affected codes: 82570, 84431

Documentation Required

LDT Validation and CLIA Compliance

Tests performed as laboratory-developed tests (LDTs) are regulated under CLIA as high-complexity tests. Laboratories must perform and document appropriate validation for any LDT used to report these results. If the laboratory cannot provide documentation of validation or does not meet CLIA high-complexity requirements, the test may be excluded from coverage consideration.

Maintain validation documentation for each LDT used
LDTs considered high-complexity under CLIA '88

Background

Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1), reducing production of thromboxane A2 (TXA2) and thereby decreasing platelet aggregation. “Aspirin resistance” refers to the failure of aspirin to suppress platelet TXA2 production and platelet activation in some patients. Urinary 11-dehydrothromboxane B2 (11dhTxB2) is a metabolite proposed as a marker of systemic TXA2 generation and has been used by assays such as AspirinWorks to infer aspirin effect; however, available evidence has not established that measuring urinary thromboxane metabolites improves clinical diagnosis or patient management.

Definitions

Aspirin resistance (AR)

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

Clinical implicationReported prevalence varies across studies; assays differ in detection and clinical usefulness remains undetermined.

Related termAR is listed in the policy terminology table as 'Aspirin resistance'.

11-dehydrothromboxane B2 (11dhTxB2)

Definition11-dehydrothromboxane B2 (11dhTxB2) is a urinary metabolite proposed to indicate the level of thromboxane A2 (TXA2) generation.

Biological contextUrinary 11dhTxB2 reflects systemic thromboxane formation and may derive substantially from non-platelet sources.

Frequency Limits

Frequency limits

Frequency limitsNo frequency limits specified in this document portion.

ImplicationNo periodic testing intervals or repetition limits are defined by this policy section.

ReferenceSee 'Frequency Limits' section of the laboratory module for policy scope.

Ordering Requirements

Documentation Required

LDTs must be validated and are regulated under CLIA

Laboratory-developed tests (LDTs) must be validated and are regulated under CLIA as high-complexity tests; LDTs are not FDA-approved or -cleared though they may be used clinically.

Step Therapy

Order only from laboratories with validated assays and CLIA high-complexity certification

Ordering should be performed by clinicians using laboratories that perform validated tests and maintain CLIA high-complexity certification; confirm the laboratory's validation and CLIA status prior to ordering.

Not Covered / Exclusions

Testing of urinary thromboxane metabolites (AspirinWorks) to evaluate aspirin resistance is explicitly categorized as not meeting coverage criteria under this policy and therefore will not be approved for medical necessity.

Tests that are not validated or that are performed in laboratories without appropriate CLIA certification may be excluded from reimbursement. Laboratory-developed tests (LDTs) are regulated by CMS under CLIA as high-complexity tests and must be validated and performed in CLIA-compliant laboratories; absence of such validation or certification can be a basis for denial of payment.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyMeasurement of Thromboxane Metabolites for ASA Resistance

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

Key ActionDo not request coverage or prior authorization for urinary thromboxane metabolite testing (AspirinWorks) to evaluate aspirin resistance because it does not meet coverage criteria.

SourceLink

On This Page

Documentation Required

Regulatory Precedence — Government Policy Override

If there is a conflict between this policy and applicable government policies (for example, Medicare NCDs or LCDs, or state Medicaid rules), the government policy takes precedence and will be used to determine coverage. Providers should reference and document the applicable NCD/LCD or state Medicaid guidance when submitting requests or appeals.

Follow Medicare NCDs/LCDs and state Medicaid rules when applicable
Document the specific government policy relied upon in the medical record and authorization/appeal submissions

Documentation Required

Laboratory Validation Documentation Required

Laboratories and ordering providers must retain documentation of test validation and CLIA status and make it available upon request. Documentation should include validation data, method descriptions, performance characteristics, and confirmation of CLIA certificate type (high-complexity). Failure to provide adequate validation or CLIA documentation may result in claim denial.

Keep validation records (methodology, performance, acceptance criteria) on file
Retain documentation of CLIA certificate showing high-complexity status
Provide documentation upon request to payer or during appeals

Assay useMeasured by assays (e.g., AspirinWorks) to infer aspirin's effect via reduction in TXA2 production.

Laboratory-developed test (LDT)

DefinitionLaboratory-developed test (LDT): a test developed and validated in-house by a laboratory and regulated by CMS under CLIA as a high-complexity test.

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

Regulatory contextLDTs are regulated under the Clinical Laboratory Improvement Amendments (CLIA '88) as high-complexity tests.

VerifyNow-Aspirin

DefinitionVerifyNow-Aspirin Assay: an FDA 510(k)-cleared qualitative assay to aid in detection of platelet dysfunction due to aspirin ingestion in citrated whole blood.

Intended useDesigned for point-of-care or laboratory settings to assess aspirin effect by measuring platelet-induced aggregation in whole blood.

Clearance dateReceived 510(k) clearance in October 2004 (FDA).

AspirinWorks

DefinitionAspirinWorks: an FDA 510(k)-cleared enzyme-linked immunoassay intended to aid in qualitative detection of aspirin effect by measuring urinary 11dhTxB2.

Intended useIntended to detect aspirin ingestion/effect in apparently healthy individuals post-ingestion by measuring urinary thromboxane metabolite.

Clearance dateReceived 510(k) clearance in May 2007 (FDA).