CurrentBlue Cross Blue Shield - NebraskaPolicy M.90

MA Specialty Testing: Hematology (Preauthorization Required)

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Policy M.90 governs preauthorization and medical necessity criteria for genetic and specialty diagnostic tests for non-cancerous hematologic conditions for Blue Cross Blue Shield - Nebraska members.

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CurrentBlue Cross Blue Shield - NebraskaPolicy M.90

MA Specialty Testing: Hematology (Preauthorization Required)

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Policy M.90 governs preauthorization and medical necessity criteria for genetic and specialty diagnostic tests for non-cancerous hematologic conditions for Blue Cross Blue Shield - Nebraska members.

Policy Summary

PayerBlue Cross Blue Shield - Nebraska

PolicyMA Specialty Testing: Hematology (Preauthorization Required)

Policy CodePolicy M.90

Change TypeNo material clinical or coverage changes

Effective DateMay 1, 2026

Next Review DateJan 1, 2027

Key ActionObtain prior authorization for specialty hematology genetic or molecular tests; individual tests must meet the policy's medical necessity criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

05-01-2026Policy effective date

Preauth requiredAuthorization requirement

Multiple groupsCovered condition groups

Multiple CPTsExample procedure codes

Fanconi panelPanel examples

Medical Necessity Criteria

Inherited Thrombophilia - Reasonable and Necessary Indications

Covered when ALL of the following apply (selected scenarios):

Member had a VTE provoked by one of specified risk factors: Member had a venous thromboembolism (VTE) provoked by at least one: provoked by a nonsurgical major transient risk factor OR provoked by pregnancy or postpartum OR provoked by combination oral contraceptive use

See definitions for nonsurgical transient risk factors

Planning to discontinue anticoagulation and specific history: Member is planning to discontinue anticoagulation after VTE AND has personal history of cerebral venous thrombosis OR splanchnic venous thrombosis

Minor provoking risk factor plus family history: Member has a minor provoking risk factor for VTE AND either has two first- or second-degree relatives with VTE OR meets both: at least one relative had VTE under age 50 AND the relative's thrombophilia status is unknown

Female planning pregnancy with high-risk relative: Member is a female planning a pregnancy AND has a first- or second-degree relative known to be homozygous for factor V Leiden OR known to be a compound heterozygote for factor V Leiden and prothrombin (F2) mutation

Member receiving systemic cancer therapy with family history: Member is receiving systemic cancer treatment AND does not have a personal history of VTE AND has a first-degree relative with VTE

ASH guideline notes testing in select cancer patients with family history

Inherited Thrombophilia - Not Medically Necessary

Not covered: F5 and F2 variant analysis is not reasonable and necessary for all other indications, including fetal loss or adverse pregnancy outcomes (examples: placental abruption, fetal growth restriction, preeclampsia)

Hemoglobinopathies - Reasonable and Necessary Indications

Covered when ONE of the following is met:

Positive hematologic screening: The member's hematologic screening results (e.g., MCV, MCH, CBC, hemoglobin electrophoresis, or DCIP) are positive for a hemoglobinopathy

Inconclusive screening: The member's hematologic screening results (e.g., MCV, MCH, CBC, hemoglobin electrophoresis, or DCIP) do not conclusively diagnose or rule out a hemoglobinopathy

Hemoglobinopathies - Not Medically Necessary

Not covered: HBA1/HBA2 and/or HBB variant analysis is not reasonable and necessary for all other indications

Hemophilia - Reasonable and Necessary Indications

Covered when ALL of the following apply (clinical OR laboratory presentation):

Clinical features: Member has any of the following clinical features of hemophilia: hemarthrosis (especially with mild or no antecedent trauma), deep-muscle hematomas, intracranial bleeding without major trauma, neonatal cephalohematoma or intracranial bleeding, prolonged oozing after procedures (tooth extraction, circumcision), prolonged/delayed bleeding post-surgery/trauma, unexplained GI bleeding or hematuria, heavy or prolonged menstrual bleeding (especially with onset at menarche), prolonged recurrent nosebleeds, or excessive bruising

Laboratory features: Normal platelet count AND prolonged activated partial thromboplastin time (aPTT) AND normal prothrombin time (PT)

Hemophilia - Not Medically Necessary

Not covered: F8 and/or F9 variant analysis is not reasonable and necessary for all other indications

Fanconi Anemia - Reasonable and Necessary Indications

Covered when ALL of the following apply:

Chromosome breakage and clinical features: Member had a positive or inconclusive chromosome breakage analysis AND displays at least one listed clinical feature (prenatal or postnatal short stature; abnormal skin pigmentation; skeletal malformations such as hypoplastic thumb or radius; microcephaly; ophthalmic anomalies; genitourinary anomalies; macrocytosis; increased fetal hemoglobin; cytopenia; progressive bone marrow failure; adult-onset aplastic anemia; myelodysplastic syndrome; acute myelogenous leukemia; early-onset solid tumors; or inordinate toxicities from chemotherapy or radiation)

Fanconi Anemia - Not Medically Necessary

Not covered: Multigene panel analysis for Fanconi anemia is not reasonable and necessary for all other indications

Other Non-cancerous Hematologic Conditions - Reasonable and Necessary Indications

Covered when ALL of the following apply:

Clinical features consistent with listed disorder: Genetic testing to establish or confirm one of the listed rare hematologic conditions may be considered reasonable and necessary when the member demonstrates clinical features consistent with the disorder

List includes aHUS, PAI-1 deficiency, Diamond-Blackfan anemia, hereditary spherocytosis, Factor deficiencies (VII, X, XI, XII, XIII) among others

Other non-specified conditions: Genetic testing for other non-cancerous hematologic conditions not specifically discussed will be evaluated by the criteria in the payer's General Approach to Genetic and Molecular Testing policy

See General Approach to Genetic and Molecular Testing policy for evaluation

Guideline-based indications and rationales

Clinical rationales and guideline-based scenarios where testing may be indicated

ASH 2023 conditional recommendations: Thrombophilia testing may be considered for: patients with VTE associated with nonsurgical major transient or hormonal risk factors; patients with cerebral or splanchnic venous thrombosis where anticoagulation would otherwise be discontinued; pregnant women with a family history (first or second degree) of high-risk thrombophilia; patients with cancer on systemic therapy at low/intermediate thrombosis risk and with a family history (first or second degree) of VTE.

sourced from ASH 2023

ASH family history definition: A positive family history is defined as having a first or second degree relative with VTE; testing may be considered when multiple family members have VTE or when affected family member was young.

Recommendation 13

ACOG pregnancy guidance: ACOG Practice Bulletin No.197 states screening for inherited thrombophilias is not recommended for women with history of fetal loss or adverse pregnancy outcomes because insufficient evidence that antepartum prophylaxis prevents recurrence.

ACOG 197 (2018, reaffirmed 2022)

Testing for inherited thrombophilia (F5/F2 variant analysis) is considered not reasonable and necessary for evaluation of fetal loss or adverse pregnancy outcomes, including but not limited to placental abruption, fetal growth restriction, or preeclampsia.

The policy references the American Society of Hematology (ASH) 2023 guideline which provides conditional recommendations for selective thrombophilia testing (for example, in patients with VTE associated with nonsurgical major transient or hormonal risk factors, cerebral or splanchnic venous thrombosis, pregnant women with a family history of high‑risk thrombophilia, and selected patients with cancer when family history is present). The ASH panel explicitly does not address or recommend testing for patients with cancer who have a personal history of VTE or who are at high risk of VTE. The policy also cites ACOG Practice Bulletin No. 197, which states that screening for inherited thrombophilias is not recommended for women with a history of fetal loss or adverse pregnancy outcomes because evidence does not support that antepartum prophylaxis prevents recurrence.

This medical policy is developed by Blue Cross Blue Shield of Nebraska to guide plan determinations and does not constitute authorization, certification, or a contract for benefits. Coverage and benefits for a particular service are determined by the terms of the applicable benefit contract; clinicians remain responsible for providing medical advice and treatment.

Each condition section in this policy specifies circumstances in which genetic testing may be considered reasonable and necessary and separately states that testing is not reasonable and necessary for all other indications not specifically listed in the applicable reasonable and necessary criteria.

Consistent with ASH guidance, routine screening of the general population for inherited thrombophilias prior to initiation of combined oral contraceptives is not recommended. ACOG likewise advises against screening for inherited thrombophilias in women with fetal loss or adverse pregnancy outcomes when the intent is to guide antepartum prophylaxis, citing insufficient evidence of benefit.

Procedure and Diagnosis Codes

Example Covered CPT CodesCPTCovered

81240	Prothrombin (F2) 20210G>A Mutation Analysis (example listed)
81241	Factor V (Leiden) Mutation Analysis (example listed)
81257	HBA1/HBA2 analysis for common deletions/variant (example listed)
81259	HBA1/HBA2 gene analysis full gene sequence (example listed)
81269	HBA1/HBA2 variant analysis (example listed)
81363	HBB duplication/deletion variants (example listed)
81364	HBB full gene sequence (example listed)
81403	F8 variant analysis / Molecular pathology procedure Level 4 (example listed)
81162	Fanconi Anemia Multigene Panel (example listed)
81406	F8 variant analysis (example listed)

1–10 of 19

1/2

Example ICD-10 Codes referencedICD-10

D68.2	Hereditary and idiopathic thrombocytopenia (example ICD list)
D68.51	Protein C deficiency (example ICD list)
D68.59	Other coagulation defects (example ICD list)
I82.90	Embolism and thrombosis of unspecified vein
R79.1	Abnormal coagulation profile
Z86.2	Personal history of other venous thrombosis and embolism
D53.9	Iron deficiency anemia, unspecified (example for hemoglobinopathy section)
D56.0	Alpha thalassemia
D56.1	Beta thalassemia
D56.3	Sickle-cell trait

1–10 of 15

1/2

CPT-PLA examplesCPT

0268U

HEM ATYP HEMOLYTIC UREMC SYND GEN SEQ ALY 15 GEN

CPT4 and molecular pathology codes listedCPT

81162	BRCA1&BRCA2 full sequence analysis / full duplication/deletion analysis (listed in panel codes)
81238	F9 full gene sequence
81240	F2 gene analysis 20210G>A variant
81241	F5 coagulation factor V analysis, Leiden variant
81257	HBA1/HBA2 analysis for common deletions/variant
81259	HBA1/HBA2 gene analysis full gene sequence
81307	PALB2 gene analysis full gene sequence (listed)
81361	HBB common variants
81362	HBB known familial variants
81363	HBB duplication/deletion variants

1–10 of 14

1/2

Covered CPT Codes / Molecular Pathology Procedure LevelsCPTCovered

81402	Molecular pathology procedure, Level 3
81403	Molecular pathology procedure, Level 4
81404	Molecular pathology procedure, Level 5
81405	Molecular pathology procedure, Level 6
81406	Molecular pathology procedure, Level 7
81407	Molecular pathology procedure, Level 8
81408	Molecular pathology procedure, Level 9
81479	Unlisted molecular pathology procedure

Prior Authorization & Billing Guidance

Prior Authorization

Preauthorization required (effective 05-01-2026)

Preauthorization is required for specialty hematology testing under this policy; effective date 05-01-2026. Individual tests require meeting the policy's medical necessity criteria as outlined in the condition-specific sections.

Preauthorization must be obtained before submission for specialty hematology tests.
Tests are subject to the medical necessity criteria in each condition section.

Prior Authorization

Prior authorization required for listed molecular/genetic codes

Prior authorization is required for the listed molecular and genetic procedure codes when submitted under this hematology specialty testing policy (examples include CPT-PLA 0268U and multiple CPT4 molecular/gene-specific codes such as 81162, 81238, 81240, 81241).

Includes CPT-PLA example 0268U.
Includes CPT4 examples 81162, 81238, 81240, 81241 and others listed in the Codes section.

Policy Background

This policy addresses diagnostic genetic testing used to confirm or establish non‑cancerous hematologic disorders, including inherited thrombophilia (Factor V Leiden and prothrombin F2 variant analysis), hemoglobinopathies (HBA1/HBA2 and HBB variant analysis), hemophilia (F8 and F9 variant analysis), Fanconi anemia multigene panels, and other hereditary hematologic conditions. It is intended to guide preauthorization and medical necessity decisions and to align testing indications with cited clinical guidelines and laboratory findings.

Key Definitions

Close relatives — degree definitions

First-degree relativesParents, siblings, and children

Second-degree relativesGrandparents, aunts/uncles, nieces/nephews, grandchildren, and half-siblings

Third-degree relativesGreat-grandparents, great aunts/uncles, great grandchildren, and first cousins

Nonsurgical transient risk factors — examples

Hospital confinement (acute illness)Confinement to bed in the hospital with acute illness for at least 3 days

Short hospital admission plus other minor factorsAdmission of less than 3 days with acute illness combined with other minor transient factors

Family History and Biomarker Conditions

Biomarker applicability — inherited thrombophilia in cancer patients

Therapeutic biomarker noteNo therapeutic biomarkers specific to treatment are required; policy includes inherited thrombophilia testing consideration for members receiving systemic cancer therapy who do not have a personal history of VTE and who have a first-degree relative with VTE

ASH guideline basisASH 2023 guideline informs selective thrombophilia testing recommendations in cancer patients with family history

Family history roleTesting in cancer patients may be considered when a first-degree relative has VTE

Family history of VTE — policy definition

Definition used for criteriaA positive family history is defined as having a first or second degree relative with VTE

ASH recommendation detail

Policy Summary

PayerBlue Cross Blue Shield - Nebraska

PolicyMA Specialty Testing: Hematology (Preauthorization Required)

Policy CodePolicy M.90

Change TypeNo material clinical or coverage changes

Effective DateMay 1, 2026

Next Review DateJan 1, 2027

Key ActionObtain prior authorization for specialty hematology genetic or molecular tests; individual tests must meet the policy's medical necessity criteria.

SourceLink

On This Page

Hemoglobinopathy gene testing indications: Molecular testing for HBA1/HBA2 and HBB is generally reserved for selected cases where basic hematology and hemoglobin analysis are inconclusive, and is important for carrier detection, genetic counseling, prenatal/preimplantation diagnosis, and predicting clinical severity.

GeneReviews and Viprakasit & Ekwattanakit 2018

Fanconi anemia testing pathway: If chromosome breakage test is positive, genetic testing should be performed to identify FA-causing variants to enable accurate diagnosis, genotype/phenotype care, and familial risk assessment.

Fanconi Anemia Research Foundation guidance

Prior Authorization

Preauthorization required for listed molecular pathology procedure levels

Preauthorization is required for molecular pathology procedure codes at the specified molecular pathology procedure levels (examples: 81402–81409 and 81479) when these procedures are submitted for reimbursement under the Fanconi anemia multigene panel and related molecular pathology listings.

Molecular pathology procedure levels include 81402 (Level 3) through 81408 (Level 9) and 81479 (unlisted).
Authorization applies when these procedure-level codes are billed for the panel.

Denial Risk

NCD/LCD determinations take precedence

National coverage determinations (NCDs) or local coverage determinations (LCDs) will be applied first when present; if an applicable NCD/LCD exists, that determination takes precedence and may result in approval or denial independent of this policy.

Providers should verify if an NCD or LCD applies before relying on this policy for coverage determinations.

Documentation Required

Quick Code Search: enter procedure + diagnosis (≥3 characters)

When using the Quick Code Search, enter the procedure code (at least first 3 characters) and the diagnosis code (at least first 3 characters) and click 'Add Code Pair' to see if a procedure/diagnosis pair will be approved, denied, or held for review.

Both a procedure and diagnosis are required for the Quick Code Search to evaluate a code pair.
Enter at least the first three characters of each code before adding the code pair.

Note

Supporting references and policy disclaimer

The Medical Policies and References section lists external resources (e.g., NCBI Bookshelf, OMIM, CDC guidance, MedlinePlus) that may be used to support clinical documentation; the policy itself does not constitute authorization, certification, or a contract for benefits.

References include NCBI Bookshelf and OMIM along with CDC and MedlinePlus resources.
Policies are used to administer plan benefits but do not constitute authorization or a contract for benefits.

Documentation Required

Codes listed are not comprehensive; consult clinical rationale

The policy notes that the tests, CPT codes, and ICD codes referenced are not comprehensive; inclusion of a code in the policy does not guarantee coverage—consult the Clinical Rationale and References for supporting context when documenting medical necessity.

Listed CPT and ICD codes are examples and not an exhaustive list.
Inclusion in the policy is not a guarantee of coverage; clinical rationale and references should be consulted when submitting documentation.

Billing Rule

Quick Code Search requires both procedure and diagnosis codes

Use the Quick Code Search by entering both a procedure code and a diagnosis code (each at least the first three characters) to determine whether a procedure/diagnosis pair will be approved, denied, or held for review.

Procedure: enter at least the first 3 characters.
Diagnosis: enter at least the first 3 characters.
Click 'Add Code Pair' to evaluate the pair.

Documentation Required

External references available to support documentation

References provided (NCBI Bookshelf, OMIM, CDC guidance, MedlinePlus) are listed to support clinical documentation; note the policy and references inform plan determinations but do not themselves constitute authorization.

Use listed external resources to support clinical rationale and documentation.
The policy is used for benefit determination; it is not an authorization or contract.

Denial Risk

Applicable NCD/LCDs supersede this policy

If a relevant NCD or LCD exists for the requested test, that determination will be applied before this policy; failure to meet this policy's medical necessity criteria does not override an applicable NCD/LCD determination.

Check for applicable NCDs/LCDs prior to submitting authorization requests.
NCD/LCDs take precedence over this payer policy.

Denial Risk

Missing code pair may prevent automated determination

A missing or not-added code pair (procedure + diagnosis) in the Quick Code Search may prevent the system from automatically determining approval, denial, or hold for review—ensure the required pairing is added.

Add the procedure and diagnosis code pair via 'Add Code Pair' to permit automated determination.
If the pair is not added or is incomplete, automated decisioning may not occur.

Prior Authorization

'Preauthorization Required' policy header — authorization required

This policy series and the policy header indicate 'Preauthorization Required'—preauthorization is required for specialty hematology testing under this policy.

The policy title and header specify that preauthorization is required for MA specialty hematology testing.

Bed confinement outside hospital

Confinement to bed outside of hospital for at least 3 days

Leg injury with decreased mobilityLeg injury associated with decreased mobility for at least 3 days

Close relatives — degree definitions

First-degree relativesParents, siblings, and children

Second-degree relativesGrandparents, aunts/uncles, nieces/nephews, grandchildren, and half-siblings

Third-degree relativesGreat-grandparents, great aunts/uncles, great grandchildren, and first cousins

Nonsurgical transient risk factors — examples

Hospital confinement (acute illness)Confinement to bed in the hospital with acute illness for at least 3 days

Combination of minor transient risk factorsExamples include admission <3 days with acute illness plus other minor transient factors

Bed confinement outside hospitalConfinement to bed outside of hospital for at least 3 days

Molecular pathology procedure — Level 3 (examples)

Scope example — multiple small variants>10 SNPs, 2–10 methylated variants, or 2–10 somatic variants (non-sequencing target variant analysis)

Immune receptor rearrangementsMay include immunoglobulin and T-cell receptor gene rearrangements

Structural/LOH assessmentsDuplication/deletion variants of 1 exon, loss of heterozygosity (LOH), uniparental disomy (UPD)

Molecular pathology procedure — Level 4 (examples)

Single-exon analysisAnalysis of a single exon by DNA sequence analysis

Multiplex ampliconsAnalysis of >10 amplicons using multiplex PCR in 2 or more independent reactions

Small multi-exon mutation/dup-delMutation scanning or duplication/deletion analysis of 2–5 exons

Molecular pathology procedures — Levels 5–9 (scope examples)

Level 5 scopeAnalysis of 2–5 exons by DNA sequence analysis, or mutation scanning/duplication-deletion of 6–10 exons

Level 6 scopeAnalysis of 6–10 exons by DNA sequence analysis, or mutation scanning/duplication-deletion of 11–25 exons

Level 7–9 progressionLevel 7: 11–25 exons; Level 8: 26–50 exons or multiple genes on one platform; Level 9: >50 exons in a single gene

Testing may be considered when multiple family members have VTE or when the affected family member was young

Application in policy scenariosPolicy criteria reference first- or second-degree relatives for pregnancy and other testing considerations