CurrentCentenePolicy N/A

Concert Genetic Testing: Hematologic Conditions (non-cancerous)

Defines medical necessity criteria for genetic testing to confirm or establish diagnoses of noncancerous hematologic conditions (inherited thrombophilia, hemoglobinopathies, hemophilia, VWF, G6PD, and other rare hematologic genetic disorders), lists example CPT and ICD-10 codes and example labs, and states investigational indications.

Policy Summary

PayerCentene

PolicyConcert Genetic Testing: Hematologic Conditions (non-cancerous)

Policy CodePolicy N/A

Change TypeRevised; clarified investigational status

Effective Date

Next Review Date

Key ActionProvide documentation of relevant clinical features and laboratory screening results when submitting claims for genetic testing and obtain prior authorization per Health Plan processes.

SourceLink

POLICY UPDATE CHANGES

VWF variant analysis clarified as investigational; diagnosis achievable by standard laboratory testing.

Updated references to 2023 ASH guidelines and updated GeneReviews copyright dates; renamed criteria for Factor VIII/F9 analysis and streamlined G6PD background.

7Primary covered condition categories

3Investigational variant CPTs (examples)

11Example CPT codes referenced

Scope: Defines medical necessity criteria for genetic testing to confirm or establish diagnoses of noncancerous hematologic conditions, including inherited thrombophilia, hemoglobinopathies, hemophilia, von Willebrand disease (VWD), G6PD deficiency, and other rare hematologic genetic disorders; lists example CPT and ICD-10 codes and laboratory screening tests, and designates certain variant analyses as investigational when not meeting criteria.

Overview: This policy provides rationale and guideline-based support for targeted genetic testing in noncancerous hematologic disorders. It references evidence-based guidance such as the 2023 ASH thrombophilia testing guidelines, ACOG guidance on inherited thrombophilias in pregnancy, GeneReviews summaries for hemoglobinopathies and hemophilia, CDC VWD diagnostic guidance, and UpToDate/other specialty sources to inform testing indications and approaches. The document explains that many diagnoses (for example, von Willebrand disease and G6PD deficiency) can be established with standard laboratory or biochemical testing and that molecular testing is reserved for situations where results would guide clinical management or when screening/biochemical testing is inconclusive or insufficient for diagnosis.

Policy metadata

StatusCURRENT

Last review2024-11

Policy numberN/A

Medical Necessity Criteria

Factor V Leiden (F5) and Prothrombin (F2) Variant Analysis for Inherited Thrombophilia (81241, 81240)

F5 and F2 variant analysis to confirm or establish an inherited thrombophilia is medically necessary when:

ANY of the following

I.A: The member/enrollee had a venous thromboembolism (VTE) provoked by a nonsurgical major transient risk factor
I.A: The member/enrollee had a venous thromboembolism (VTE) provoked by pregnancy or postpartum
I.A: The member/enrollee had a venous thromboembolism (VTE) provoked by combination oral contraceptive use
I.B
- AND has one of
  - History of cerebral venous thrombosis
  - History of splanchnic venous thrombosis
I.C
- AND
  - The member/enrollee has two first- or second-degree relatives with VTE
  - At least one relative had VTE under age 50
  - The relative's thrombophilia status is unknown
I.D (female planning pregnancy)
- AND has one of
  - A first- or second-degree relative known to be homozygous for factor V Leiden
  - A first- or second-degree relative known to be a compound heterozygote for factor V Leiden and prothrombin (F2) mutation
I.E (receiving systemic cancer treatment)
- Does not have a personal history of VTE
- Has a first-degree relative with VTE

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HBA1/HBA2 and/or HBB Variant Analysis for Hemoglobinopathies (81257, 81259, 81269, 81363, 81364)

HBA1/HBA2 and/or HBB variant analysis to confirm or establish hemoglobinopathy is medically necessary when:

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Factor VIII (F8) and Factor IX (F9) Variant Analysis for Hemophilia A and B (81403, 81406, 81407, 81238, 81479)

F8 and/or F9 variant analysis to confirm or establish hemophilia A or B is medically necessary when:

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VWF Variant Analysis (81408, 81479)

VWF variant analysis to confirm or establish von Willebrand disease:

VWF variant analysis is considered investigational; diagnosis of VWD can be achieved by standard laboratory and biochemical testing

Other Covered Hematologic Conditions (noncancerous)

Genetic testing to establish or confirm diagnosis to guide management is medically necessary when the member demonstrates clinical features consistent with the disorder (list not comprehensive):

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G6PD Variant Analysis (81247, 81248, 81249, 81479)

G6PD variant analysis to confirm or establish G6PD deficiency:

G6PD variant analysis is considered investigational; diagnosis can be achieved by quantitative spectrophotometric analysis or rapid fluorescent spot test detecting NADPH generation

Coding

Inherited Thrombophilia example CPTCPTCovered

81241	F5 (Factor V) variant analysis (Factor V Leiden) - referenced
81240	F2 (Prothrombin) variant analysis - referenced

Hemoglobinopathies example CPTCPTCovered

81257	HBA1 single gene analysis / Alpha-globin mutation analysis - referenced
81259	HBA2 or multi HBA analysis - referenced
81269	HBA1/HBA2 related assay - referenced
81363	HBB gene dosage analysis - referenced
81364	HBB sequencing - referenced

Hemophilia example CPTCPTCovered

81403	F8 variant analysis (large gene panels/seq) - referenced
81406	F8 analysis (complex) - referenced
81407	F8 analysis (complex) - referenced
81238	F9 variant analysis - referenced
81479	Unlisted molecular pathology procedure (used in examples)

VWF Variant Analysis CPTCPTNot Covered

81408	VWF gene sequencing - listed as investigational
81479	Unlisted molecular pathology (used as example); VWF also referenced with 81479

G6PD Variant Analysis CPTCPTNot Covered

81247	G6PD targeted variant analysis
81248	G6PD full gene sequencing
81249	G6PD deletion/duplication analysis
81479	Unlisted molecular pathology (example usage)

Other covered panel CPTs (examples listed)CPTCovered

81400	Molecular pathology CPT example listed in Other Covered Hematologic Conditions
81401	Molecular pathology CPT example
81402	Molecular pathology CPT example
81403	Molecular pathology CPT example (also in Hemophilia)
81404	Molecular pathology CPT example
81405	Molecular pathology CPT example
81406	Molecular pathology CPT example (also in Hemophilia)
81407	Molecular pathology CPT example (also in Hemophilia)
81408	Molecular pathology CPT example (VWF) - investigational per policy text

Common ICD-10 examples referencedICD-10

D68.51	Inherited thrombophilia (example referenced)
D68.52	Other thrombophilia (example referenced)
D68.2	Other venous embolism and thrombosis
D56.0	Alpha thalassemia (example referenced)
D56.9	Thalassemia, unspecified
D57	Sickle-cell disorders
D66	Hereditary factor VIII deficiency (Hemophilia A)
D67	Hereditary factor IX deficiency (Hemophilia B)
D55.0	G6PD deficiency
D68.0	von Willebrand disease

1–10 of 13

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Provider Actions

Documentation Required

Document clinical features and lab results

When submitting claims for genetic testing, provide documentation of relevant clinical features (for example: details of venous thromboembolism events, bleeding symptoms such as hemarthrosis, deep‑muscle hematomas, intracranial bleeding, heavy or prolonged menstrual bleeding, recurrent/prolonged nosebleeds, excessive bruising) and relevant laboratory screening results (examples: MCV, MCH, CBC, hemoglobin electrophoresis, DCIP, aPTT, PT, platelet count). Documentation should demonstrate that the member meets the policy clinical and laboratory criteria for the requested genetic test.

Document clinical features relevant to the suspected hematologic condition (e.g., VTE details, bleeding manifestations).
Attach laboratory screening results that support testing criteria (examples: MCV, MCH, CBC, hemoglobin electrophoresis, DCIP, aPTT, PT, platelet count).
Ensure documentation maps to the policy's specified medical necessity criteria for the requested variant analysis.

Prior Authorization

Prior authorization likely required per plan

Prior authorization is likely required per the member's plan. Obtain prior authorization through the Health Plan process before ordering testing. Use the Concert Platform to confirm whether a specific test is registered and to check coverage details for that test prior to claim submission.

Obtain prior authorization per plan requirements before testing.
Check the Concert Platform for registered tests and coverage information prior to submitting claims.

Denial Risk

Investigational indications denied

Claims for variant analyses designated investigational in this policy (examples include VWF gene sequencing and related unlisted molecular pathology, and G6PD variant analyses) may be denied as not medically necessary. Example CPT codes listed as investigational or not covered include 81408, 81247, 81248, 81249, and 81479; claims for these tests for investigational indications may be denied.

Investigational example CPTs: 81408 (VWF sequencing), 81247, 81248, 81249 (G6PD variant analyses), and 81479 (unlisted molecular pathology).
Claims for variant analyses designated investigational in the policy may be denied as not medically necessary.

Background and Evidence

Background summary of guideline support and rationale: The policy cites the ASH 2023 recommendations for selective thrombophilia testing in defined scenarios and ACOG guidance limiting screening in adverse pregnancy outcomes; it references GeneReviews for hemoglobinopathies and hemophilia diagnostic pathways and the CDC VWD guidance that does not recommend routine genetic testing for VWD. The rationale emphasizes that many hematologic conditions can be diagnosed using standard laboratory or biochemical tests (examples cited include MCV/MCH/CBC, hemoglobin electrophoresis/DCIP for hemoglobinopathies; quantitative spectrophotometric or rapid fluorescent spot testing for G6PD), and states that genetic testing is indicated when it will directly guide management or when screening tests are inconclusive or do not establish a diagnosis.

Source	Notes
ASH 2023 guidelines	Provides conditional recommendations supporting thrombophilia testing in specific scenarios (patients with VTE provoked by nonsurgical major transient or hormonal risk factors; cerebral or splanchnic venous thrombosis when anticoagulation would otherwise be discontinued; family history considerations; pregnant women with family history of high-risk thrombophilia; cancer patients on systemic therapy with family history).
GeneReviews	Authoritative summaries supporting diagnostic pathways for hemoglobinopathies and hemophilia; recommends molecular testing when hematologic screening is positive or inconclusive and outlines clinical/laboratory features prompting testing.
CDC VWD guidance	States genetic testing is not included as a routine diagnostic method for von Willebrand disease; diagnosis can be achieved by standard laboratory and biochemical testing.

Definitions

Brief thresholds / diagnostic examples

Revision History

11/2024revisedLatest

Updated references to 2023 ASH guidelines and updated GeneReviews copyright dates; renamed criteria for Factor VIII/F9 analysis and streamlined G6PD background. (editorial)

04/2024revised

Semi-annual review: minor rewording for clarity, moved known familial variant criteria to consolidated policy, updated coding and reference table. (editorial)

10/2023revised

Policy updates during semi-annual review: overview, coding, reference-table, background and references updated; adjustments to Hemoglobinopathies and Hemophilia reference/test listings. (editorial)

03/2023revised

Policy developed and approved; semi-annual review and initial content establishment including coding implications and criteria. (editorial)

clarified

VWF variant analysis clarified as investigational; diagnosis achievable by standard laboratory testing. (material)

clarified

Example test updates in Policy Reference Table for VWF and G6PD (renamed/streamlined entries). (editorial)

OpenPayer

Concert Genetic Testing: Hematologic Conditions (non-cancerous)

Coverage Summary

Medical Necessity Criteria

Coding

Provider Actions

Background and Evidence

Revision History