ModifiedHealth NetPolicy CP.PHAR.222

Factor XIII A-Subunit; Recombinant (Tretten)

Policy governing medical necessity and prior authorization criteria for Tretten (recombinant factor XIII A-subunit) for routine prophylaxis of bleeding in members with congenital Factor XIII A-subunit deficiency across Health Net lines of business.

Policy Summary

PayerHealth Net

PolicyFactor XIII A-Subunit; Recombinant (Tretten)

Policy CodePolicy CP.PHAR.222

Change TypeRevisions to documentation and approval durationsclarifications and exclusions

Effective Date05.01.16

Next Review Date

Key ActionSubmit prior authorization with documentation that the member has congenital Factor XIII A-subunit deficiency and meets initial approval criteria, including hematology consultation and required lab/bleed history for new prophylaxis starts.

SourceLink

POLICY UPDATE CHANGES

Clarified requirement for coverage of factor XIIIa for routine prophylaxis: the requirement for factor XIII activity level documentation of bleed history only applies to requests for new starts to routine prophylactic therapy.

For Commercial line of business, revised initial and continued approval durations to be '6 months or to the member's renewal date, whichever is longer;' for Medicaid and HIM lines, continued approval duration revised from 6 months to 12 months.

Enhanced existing requirement by excluding coverage for B-subunit disease and focusing coverage on A-subunit disease.

Updated sites of serious bleeds per WFH guideline in Appendix D.

Removed the word 'life-threatening' from the 'life-threatening or serious bleed' criterion.

35 IU/kgstandard prophylactic dose

10%target trough

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6 moinitial approval (typ.)

12 mocontinued approval (Medicaid/HIM)

1Q 2025most recent review

Coverage Criteria

inv-01: Initial Therapy — Covered when ALL of the following are met

Covered when ALL of the following are met

Initial Approval: 1. Diagnosis of congenital Factor XIII A-subunit deficiency; 2. Prescribed by or in consultation with a hematologist; 3. Request is for routine prophylaxis to prevent or reduce the frequency of bleeding episodes; 4. For routine prophylaxis, member meets ONE of the following: (a) member has previously used factor XIIIa for routine prophylaxis; (b) member has severe hemophilia (defined as factor level of 1%); (c) member has experienced at least one serious spontaneous bleed (see Appendix D).

Items consolidated from policy section I Initial Approval Criteria.

inv-02: Continuation Therapy — Covered for continuation when ONE of the following is met

Covered for continuation when ONE of the following is met

Continuation Therapy: a. Member is currently receiving medication via Centene benefit; OR b. Member has previously met initial approval criteria and the member is responding positively to therapy.

Continuation criteria per section II Continued Therapy.

inv-03: Policy-level coverage criteria and administrative parameters — policy-level clarifications and recent changes

Policy-level coverage parameters and recent clarifications

A-subunit disease requirement: Coverage is limited to Factor XIII A-subunit disease; congenital Factor XIII B-subunit deficiency is excluded.

Enhanced requirement applied 1Q 2021.

Documentation for new prophylaxis starts: Requests for new starts to routine prophylactic therapy must include documentation of Factor XIII activity level and bleed history.

Clarified in 1Q 2022 review.

Approval durations: Commercial: initial and continued approvals are 6 months or to the member's renewal date, whichever is longer. Medicaid/HIM: continued approval duration is 12 months.

Revised in 1Q 2025 review.

This policy applies to replacement therapy for members with a confirmed diagnosis of congenital Factor XIII A-subunit deficiency. Coverage is limited to use of recombinant Factor XIII A-subunit (Tretten) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes when the member meets the documented initial approval criteria and dosing guidance. For new starts of routine prophylaxis, providers must submit documentation of Factor XIII activity level and relevant bleed history as specified in the policy.

Coverage is excluded for members with congenital Factor XIII B-subunit deficiency. Requests for treatment of B‑subunit disease will not be authorized under this policy and may be denied unless supported by the applicable off‑label use policy or separate evidence of coverage documentation.

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the request is supported by sufficient documentation of efficacy and safety per the applicable off‑label use policy (see CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or other evidence of coverage.

The policy language was clarified to remove the term "life‑threatening" from the phrase "life‑threatening or serious bleed" to avoid potential misinterpretation. This change ensures that criteria referring to a serious bleed are applied using the clinical definitions in the policy without conflating distinct severity labels.

Initial Therapy and Dosing

inv-25: Initial Therapy and Dosing — Initial therapy coverage and dosing

Initial therapy coverage and dosing

Initial dosing and criteria: Dose: 35 IU/kg IV once monthly for routine bleeding prophylaxis to achieve a target trough Factor XIII activity >= 10%. Consider dose adjustment if adequate coverage is not achieved with the 35 IU/kg dose. Member must have congenital Factor XIII A-subunit deficiency and therapy must be prescribed by or in consultation with a hematologist; request must be for routine prophylaxis per Initial Approval criteria.35 IU/kg monthly; trough >= 10%

Vial strengths available 2,000–3,125 IU.

inv-26: Initial therapy criteria — Requirements for initiating routine prophylaxis

Requirements for initiating routine prophylaxis

New prophylaxis initiation: For new starts to routine prophylactic therapy, documentation must include Factor XIII activity level and bleed history to support the request.

Continuation Criteria

inv-27: Continuation — Continuation therapy coverage

Continuation therapy coverage

Continuation: Member is currently receiving medication via Centene benefit OR has previously met initial approval criteria; member must be responding positively to therapy.

Approval duration differs by line of business; see continued therapy durations.

inv-28: Continued therapy durations — Continued approval duration varies by line of business

Continued approval duration varies by line of business

Commercial continued approval: 6 months or to the member's renewal date, whichever is longer.

Applied in 1Q 2025 review.

Medicaid/HIM continued approval:

Coding and Billing

HCPCS CodesHCPCS

J7181

Injection, factor XIII A-subunit (recombinant), per IU

inv-09: Target trough Factor XIII activity

Target trough Factor XIII activity>= 10%

PurposeTarget trough used to guide dosing for routine bleeding prophylaxis

Dose relationStandard prophylactic dose 35 IU/kg IV once monthly aims to achieve this trough

inv-10: approval duration (Commercial)

Commercial approval duration6 months or to the member's renewal date, whichever is longer

Applies toInitial and continued approvals for Commercial line of business (per 1Q 2025 review)

Provider Actions and Prior Authorization

Prior Authorization

Prior Authorization Required

Prior authorization requirement — Documentation that member has congenital factor XIII A-subunit deficiency and meets initial approval criteria is required

Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all approval criteria.
Requests for non‑FDA approved indications not addressed in this policy may be denied unless sufficient documentation per applicable off‑label use policies (CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, CP.PMN.53 for Medicaid) is provided.
Requests for congenital factor XIII B‑subunit deficiency are not authorized and may be denied.

Note

Authorization Durations

Prior authorization requirements and durations — Prior authorization durations revised and noted by line of business

Initial and continued approval durations for Commercial: 6 months or to the member's renewal date, whichever is longer.

Step Therapy

Step	Requirement / Policy Note
1	No explicit step therapy sequence is described in this policy. The policy clarifies wording related to bleed severity: the phrase 'life‑threatening or serious bleed' was revised by removing 'life‑threatening' to avoid misinterpretation (applied 1Q 2023).

Site of Care

Note

Hospital outpatient: sites of serious bleeds updated per WFH; no site‑of‑care restrictions

Sites of serious bleeds referenced in the policy were updated per the World Federation of Hemophilia guideline (Appendix D); the policy does not impose specific site‑of‑care utilization restrictions for hospital outpatient settings in these sections.

WFH Appendix D used to define sites of serious bleeds
No site‑of‑care utilization restrictions stated

Quantity Limits

inv-30: Tretten — quantity / product reference (vial strengths and related limits)

Available vial strengthsPowder for reconstitution in single-use vials: 2,000 to 3,125 IU

Unit labelingActual IU amount is stated on each carton and vial and may vary by vial

ProductTretten (recombinant Factor XIII A-subunit)

Definitions

inv-21: Spontaneous bleed — definition

DefinitionA spontaneous bleed is a bleeding episode that occurs without apparent cause and is not the result of trauma.

ContextUsed to distinguish spontaneous events from trauma-related bleeding in prophylaxis criteria

Source appendixAppendix D: General Information

inv-22: Serious spontaneous bleed — definition and example anatomic sites

DefinitionSerious spontaneous bleed includes bleeds in intracranial; neck/throat; gastrointestinal; joints (hemarthrosis); deep muscles (eg, iliopsoas, calf, forearm); or mucous membranes (mouth, nose, genitourinary).

Clinical implicationOccurrence of a serious spontaneous bleed can meet criteria for initiation of routine prophylaxis

Background

Factor XIII A‑subunit deficiency is a congenital bleeding disorder for which recombinant Factor XIII A‑subunit (Tretten) is indicated for routine prophylaxis to prevent bleeding. The policy specifies use for congenital Factor XIII A‑subunit deficiency, requires hematology prescribing or consultation for initial approval, and mandates documentation (including Factor XIII activity level and bleed history) for new prophylaxis starts. Treatment dosing guidance and target troughs are provided elsewhere in the policy.

Policy Summary

PayerHealth Net

PolicyFactor XIII A-Subunit; Recombinant (Tretten)

Policy CodePolicy CP.PHAR.222

Change TypeRevisions to documentation and approval durationsclarifications and exclusions

Effective Date05.01.16

Next Review Date

SourceLink

On This Page

Clarified requirement applied 03.03.22.

12 months continued approval.

Applied in 1Q 2025 review; Medicaid/HIM continued approval duration revised from 6 months to 12 months.

02.25 (1Q 2025 annual review)

inv-11: continued approval duration (Medicaid/HIM)

Medicaid/HIM continued approval duration12 months

Change summaryRevised from 6 months to 12 months for Medicaid/HIM (1Q 2025 review)

P&T approval date02.25 (1Q 2025 annual review)

Continued approval duration for Medicaid and HIM: 12 months.

Documentation Required

Continuation Criteria

Continuation requires member currently receiving medication via Centene benefit or prior meeting of initial criteria and response

Continuation (renewal) is authorized when the member is currently receiving the medication via a Centene benefit or previously met the initial approval criteria and is responding positively to therapy.
Members enrolled in a state/product with continuity of care regulations may have continuation considered under those rules—refer to state specific addendums.

Documentation Required

Required Documentation for Continuation / New Prophylaxis Starts

Continuation requires documentation of response and, for new starts of routine prophylaxis, documentation of Factor XIII activity level and bleed history

For continuation requests, submit recent clinical documentation demonstrating a positive response to therapy (e.g., improvement in bleeding frequency/severity, clinician notes).
New starts to routine prophylactic therapy must include documentation of Factor XIII activity level and bleed history as specified in the policy (see Appendix D for definitions of serious bleeds).

Step Therapy

Criteria Clarifications

Step therapy/criteria wording — Clarifications removed 'life‑threatening' language; no explicit step therapy algorithm provided

No explicit step‑therapy algorithm is required by this policy; criteria focus on diagnosis, specialist involvement, prior use, and bleed history.
The policy language was clarified to remove the term 'life‑threatening' from the 'serious bleed' criterion to avoid ambiguity.

Denial Risk

Denial Triggers / Coding Risk

Denial triggers — Requests for non‑covered indications, for B‑subunit disease, or lacking required documentation may be denied

Denial may occur if documentation does not demonstrate congenital factor XIII A‑subunit deficiency or failure to meet initial/continuation criteria.
Denial may occur for requests for congenital factor XIII B‑subunit deficiency, which is explicitly excluded from coverage in Section III.
Denial may occur for non‑FDA approved indications that lack sufficient supporting evidence per applicable off‑label use policies.
Claims may be denied if coding submitted is not aligned with professional coding guidance; inclusion/exclusion of codes in the policy does not guarantee coverage.

Source appendixAppendix D: General Information

inv-23: World Federation of Hemophilia guidelines reference for sites of serious bleeds

Guideline referencedWorld Federation of Hemophilia (WFH) guidelines for the management of hemophilia (Haemophilia: 2020,26[suppl 6]:1-158)

Use in policyWFH guidelines used as reference for defining sites of serious bleeds (see Appendix D)

Access noteWFH guidelines cited in policy references list (Tre tten PI also referenced)

inv-24: MASAC — guideline source reference

Guideline sourceMedical and Scientific Advisory Council (MASAC) of the National Bleeding Disorders Foundation

RoleListed as a referenced guideline source in the policy's references/database of treatment guidelines

Access informationReferenced database available via the National Bleeding Disorders Foundation website (MASAC documents)