ModifiedUnitedHealthcarePolicy IEXD0047.04

Clotting Factors, Coagulant Blood Products, & Other Hemostatics

Medical benefit drug policy governing coverage of branded clotting factor and related hemostatic products for Individual Exchange benefit plans (excludes MA, NV, NY). Affects providers prescribing or requesting authorization for listed products.

Policy Summary

PayerUnitedHealthcare

PolicyClotting Factors, Coagulant Blood Products, & Other Hemostatics

Policy CodePolicy IEXD0047.04

Change TypeOperational updates and reference revisions

Effective DateJan 1, 2026

Next Review Date

Key ActionObtain prior authorization demonstrating the covered diagnosis and intended treatment intent for listed branded clotting factor products.

SourceLink

POLICY UPDATE CHANGES

Removed reference link to the Medical Benefit Drug Policy titled Review at Launch for New to Market Medications for Alhemo (concizumab-mtci).

Updated FDA and References sections to reflect the most current information.

~40brand products listed

All minus 3geographic applicability

Hemophilia A & Bprimary covered diagnoses

>=12min age for non-factor therapies

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.

>=5 BUhigh-titer inhibitor threshold

Coverage Criteria by Indication and Product

Congenital Factor XIII Deficiency — Corifact

Covered when BOTH criteria are met

Corifact coverage: Diagnosis of congenital factor XIII deficiency; AND one of: routine prophylactic treatment OR peri-operative management of surgical bleeding OR treatment of bleeding episodes

Congenital Factor XIII A-subunit Deficiency — Tretten

Covered when BOTH criteria are met

Tretten coverage: Diagnosis of congenital factor XIII A-subunit deficiency; AND one of: routine prophylactic treatment OR peri-operative management of surgical bleeding OR treatment of bleeding episodes

Von Willebrand Disease — Humate-P

Humate-P is proven when criteria below are met

Diagnosis criteria: Either diagnosis of severe von Willebrand disease; OR (diagnosis of mild or moderate VWD AND history of failure, contraindication, or intolerance to desmopressin)

Treatment intent: Treatment of bleeding episodes OR peri-operative management of surgical bleeding

Both diagnosis and treatment intent must be met

Von Willebrand Disease — Alphanate

Covered when ALL criteria are met

Alphanate coverage: Diagnosis of mild or moderate von Willebrand disease; AND peri-operative management of surgical bleeding; AND history of failure, contraindication, or intolerance to desmopressin

Von Willebrand Disease — Wilate and Vonvendi

Covered when BOTH criteria are met

Wilate coverage: Diagnosis of von Willebrand disease; AND one of: routine prophylactic treatment OR peri-operative management of surgical bleeding OR treatment of bleeding episodes

Vonvendi coverage: Diagnosis of von Willebrand disease; AND one of: routine prophylactic treatment OR peri-operative management of surgical bleeding OR treatment of bleeding episodes

Vonvendi additionally is FDA-labeled for routine prophylaxis in adults

Congenital Factor VII Deficiency — NovoSeven RT

Covered when BOTH criteria are met

NovoSeven coverage: Diagnosis of congenital factor VII deficiency; AND one of: routine prophylactic treatment OR treatment of bleeding episodes

Hemophilia A — Multiple Factor VIII Products

Covered when BOTH criteria are met for listed products

Hemophilia A general: Diagnosis of hemophilia A; AND one of: routine prophylactic treatment OR peri-operative management of surgical bleeding OR treatment of bleeding episodes

Applies to listed plasma-derived and recombinant factor VIII products including Alphanate, Humate-P, Hemofil M, Koāte-DVI, Advate, Kogenate FS, Kovaltry, NovoEight, Nuwiq, Recombinate, Wilate, Esperoct, Xyntha, Eloctate, Altuviiio, Jivi

Altuviiio (antihemophilic factor Fc-VWF-XTEN fusion protein-ehtl)

Proven when both of the following criteria are met

ALL of the following

Diagnosis of hemophilia A
Indication: One of: routine prophylactic treatment; peri-operative management of surgical bleeding; treatment of bleeding episodes

Jivi (antihemophilic factor, pegylated-aucl)

Proven when all of the following criteria are met

ALL of the following

Diagnosis of hemophilia A
Indication: One of: routine prophylactic treatment; peri-operative management of surgical bleeding; treatment of bleeding episodes
Prior factor VIII: Patient has previously received Factor VIII replacement therapy
Age: Patient is 7 years of age or older

Afstyla (antihemophilic factor, single chain)

Proven when both of the following criteria are met

ALL of the following

Diagnosis of hemophilia A
Indication: One of: routine prophylactic treatment; peri-operative management of surgical bleeding; treatment of bleeding episodes

Adynovate (antihemophilic factor, pegylated)

Proven when both of the following criteria are met

ALL of the following

Diagnosis of hemophilia A
Indication: One of: routine prophylactic treatment; peri-operative management of surgical bleeding; treatment of bleeding episodes

FEIBA (anti-inhibitor coagulant complex, plasma-derived) — Hemophilia A

Proven when all of the following criteria are met

ALL of the following

Diagnosis of hemophilia A
Inhibitors: Documentation of inhibitors (e.g., Bethesda inhibitor assay)
Indication: One of: routine prophylactic treatment; peri-operative management of surgical bleeding; treatment of bleeding episodes

NovoSeven RT and Sevenfact (factor VIIa recombinant) and Obizur (porcine sequence) — acquired hemophilia

Proven when all of the following are met

ANY of the following

NovoSeven RT: Diagnosis of hemophilia A; documentation of inhibitors; indication: treatment of bleeding episodes or peri-operative management
Sevenfact: Diagnosis of hemophilia A; treatment and control of bleeding episodes
NovoSeven RT / Obizur acquired: Diagnosis of acquired factor VIII hemophilia; treatment or prevention of bleeding episodes

Factor IX products — Hemophilia B

Proven when both of the following criteria are met

ANY of the following

Plasma-derived Factor IX (AlphaNine SD or Profilnine SD): Diagnosis of hemophilia B; one of: routine prophylactic treatment; treatment of bleeding episodes
Recombinant Factor IX (BeneFIX, Rixubis, Alprolix, Idelvion): Diagnosis of hemophilia B; one of: routine prophylactic treatment; peri-operative management; treatment of bleeding episodes
Ixinity, Rebinyn: Diagnosis of hemophilia B; one of: routine prophylactic treatment; peri-operative management; treatment of bleeding episodes

FEIBA and Sevenfact / NovoSeven RT — Hemophilia B with inhibitors

Proven when all of the following are met

ALL of the following

Diagnosis of hemophilia B
Inhibitors: Documentation of inhibitors (e.g., Bethesda inhibitor assay)
Indication: One of: routine prophylactic treatment; peri-operative management; treatment of bleeding episodes (or for NovoSeven RT: treatment of bleeding episodes or peri-operative management)

Non-factor replacement therapies (Concizumab/Alhemo, Emicizumab/Hemlibra, Marstacimab/Hympavzi, Fitusiran/Qfitlia)

Proven and medically necessary for routine prophylaxis when specified criteria are met

Initial therapy

Alhemo initial A: Diagnosis of hemophilia A AND either not developed high-titer factor VIII inhibitors (>=5 BU) OR has developed high-titer inhibitors; patient is >=12 years; prescribed for routine prophylaxis
Alhemo initial B: Diagnosis of hemophilia B AND either not developed high-titer factor IX inhibitors (>=5 BU) OR has developed high-titer inhibitors; patient is >=12 years; prescribed for routine prophylaxis
Hemlibra initial: Diagnosis of hemophilia A AND either not developed high-titer factor VIII inhibitors (>=5 BU) OR has developed high-titer inhibitors; prescribed for routine prophylaxis

Fibrinogen concentrate (Fibryga, RiaSTAP)

Proven when both of the following criteria are met

ALL of the following

Diagnosis: Acquired fibrinogen deficiency OR congenital fibrinogen deficiency (afibrinogenemia, hypofibrinogenemia) (Fibryga accepts either acquired or congenital); RiaSTAP requires congenital fibrinogen deficiency
Indication: Treatment of bleeding episodes

Fibrinogen (RiaSTAP) coverage

Products described as 'proven' when criteria are met:

Fibrinogen concentrate (plasma-derived,RiaSTAP): Covered when ALL of the following are met: Diagnosis of congenital fibrinogen deficiency (afibrinogenemia or hypofibrinogenemia) AND treatment of bleeding episodes.

Source states proven when both criteria met.

Glanzmann Thrombasthenia — NovoSeven RT

Covered when ALL of the following are met:

Factor VIIa (recombinant, NovoSeven RT) for Glanzmann thrombasthenia: Diagnosis of Glanzmann thrombasthenia AND refractory to platelet transfusions AND (treatment of bleeding episodes OR peri-operative management of surgical bleeding).

Exact logic preserved from policy text.

Congenital Factor X deficiency — Coagadex

Covered when BOTH of the following are met:

Coagulation Factor X (human) (Coagadex): Diagnosis of congenital Factor X deficiency AND one of: routine prophylactic treatment OR treatment of bleeding episodes OR peri-operative management of surgical bleeding.

Second element is an OR group per source.

Evidence-based coverage groups (trial-aligned)

Clinical evidence supports coverage when prophylaxis or treatment matches studied populations and dosing regimens:

Emicizumab prophylaxis evidence: Patients with hemophilia A (age ≥12) switched from episodic treatment or prior FVIII prophylaxis to emicizumab had 96-97% lower treated bleeding rates versus no prophylaxis; more than half had no treated bleeds on prophylaxis.maintenance dosing 1.5 mg/kg weekly or 3.0 mg/kg every 2 weeks

safety: no thrombotic or TMA events reported in trial

Altuviiio (recombinant FVIII Fc) prophylaxis evidence: Weekly 50 IU/kg routine prophylaxis associated with mean ABR ~0.7 and intra-subject 77% reduction vs pre-study FVIII prophylaxis; target joints resolved in all subjects with 12 months of prophylaxis.50 IU/kg IV once weekly

supports use in PTPs with severe hemophilia A

rFVIIIFc (Eloctate) evidence:

Professional society-based coverage criteria

Covered when aligning with professional society suggestions and FDA indications:

VWD patients with severe/frequent bleeds: Suggest using long-term prophylaxis rather than no prophylaxis.

Desmopressin trial in type 1 VWD: For patients for whom desmopressin is a valid option (primarily type 1 VWD) and baseline VWF < 0.30 IU/mL, perform a desmopressin trial and treat based on results rather than skip trial and treat with tranexamic acid or factor concentrate.baseline VWF < 0.30 IU/mL

Perioperative target levels: Target both FVIII and VWF activity levels ≥ 0.50 IU/mL for at least 3 days after surgery; do not rely on FVIII ≥ 0.50 IU/mL alone.≥ 0.50 IU/mL for 3 days

FDA-labeled product considerations

Coverage and use should consider FDA-labeled indications for products:

Products not indicated for VWD: Multiple recombinant and factor VIII/FIX products are FDA-labeled for hemophilia A or B and explicitly noted as not indicated for treatment of von Willebrand disease (examples listed in FDA section).

Products indicated for VWD: Humate-P, Alphanate (for certain VWD perioperative uses), Vonvendi, and Wilate have FDA labeling for treatment and/or perioperative management in VWD; Vonvendi is additionally FDA-labeled for routine prophylaxis in adults. Use of products should align with their FDA indications.

This Medical Benefit Drug Policy applies to Individual Exchange benefit plans in all states except for Massachusetts, Nevada, and New York. Requests for members enrolled in plans governed by those states should be evaluated using the applicable state-specific benefit documents and policies.

Marstacimab (brand name Hympavzi) is specified in this policy for routine prophylaxis only in patients who do not have factor VIII or factor IX inhibitors. The policy requires documentation that the patient has not developed high‑titer inhibitors (≥ 5 Bethesda units) when used for hemophilia A, and similarly that patients with hemophilia B have not developed high‑titer factor IX inhibitors when Hympavzi is considered for that indication.

Inclusion of a product or procedure code in this policy does not by itself guarantee coverage or payment. Benefit coverage depends on the member-specific benefit plan document and applicable federal or state laws; some Certificates of Coverage or state mandates may allow additional coverage (for example, for investigational uses) under defined circumstances. Providers must verify member benefits and applicable mandates before assuming coverage.

Clinical trial definitions of a non‑successful treatment for von Willebrand disease (VWD) episodes included one or more of the following: concurrent use of another VWF‑containing product during the episode (excluding whole blood), requirement for a blood transfusion during the episode, a sustained daily dosage ≥50% above the initial required dose during follow‑up (for episodes needing >1 day), or treatment duration exceeding severity‑based limits (e.g., >4 days for severe bleeding, >3 days for moderate, >2 days for minor bleeding; gastrointestinal bleeding permitted longer). A final efficacy rating of moderate or none was also considered non‑successful.

Fixed‑dose regimens of fitusiran used in the randomized studies led to episodes of excessive clotting and therefore are not approved. The approved regimen uses an antithrombin‑based adjustable dosing strategy informed by periodic antithrombin activity measurements; prior authorization and dosing documentation should reflect use of the antithrombin‑guided regimen rather than fixed monthly dosing.

Many recombinant factor VIII and factor IX concentrates and other factor products listed in the policy are FDA‑labeled for hemophilia A or B and are not indicated for treatment of von Willebrand disease. Providers should align requests for VWD‑specific indications with products that have FDA labeling for VWD (for example, Humate‑P, Vonvendi, Wilate) and document why a non‑VWD‑labeled product would be appropriate if requested.

Per the FDA product labeling, Humate‑P is not indicated for prophylaxis of spontaneous bleeding episodes in von Willebrand disease. Humate‑P is indicated for treatment and prevention of bleeding related to surgery and for treatment of spontaneous or trauma‑induced bleeding, but not for routine prophylaxis to prevent spontaneous bleeds in VWD.

Applicable Codes and Key Coding Thresholds

Applicable HCPCS J-codesHCPCS

J7170	Injection, emicizumab-kxwh, 0.5 mg.
J7172	Injection, marstacimab-hncq, 0.5 mg.
J7173	Injection, concizumab-mtci, 0.5 mg.
J7174	Injection, fitusiran, 0.04 mg.
J7175	Injection, factor X (human), 1 i.u..
J7177	Injection, human fibrinogen concentrate (Fibryga), 1 mg.
J7178	Injection, human fibrinogen concentrate, not otherwise specified, 1 mg.
J7179	Injection, von Willebrand factor (recombinant), (Vonvendi), 1 i.u. vWF: RCo.
J7180	Injection, factor XIII (antihemophilic factor, human), 1 i.u..
J7181	Injection, factor XIII A-subunit, (recombinant), per i.u. (Tretten).

1–10 of 38

1/4

Applicable ICD-10 CodesICD-10

D66	Hereditary factor VIII deficiency.
D67	Hereditary factor IX deficiency.
D68.00	Von Willebrand's disease, unspecified.
D68.01	Von Willebrand disease, type 1.
D68.020	Von Willebrand disease, type 2A.
D68.021	Von Willebrand disease, type 2B.
D68.022	Von Willebrand disease, type 2M.
D68.023	Von Willebrand disease, type 2N.
D68.029	Von Willebrand disease, type 2, unspecified.
D68.03	Von Willebrand disease, type 3.

1–10 of 15

1/2

inv-33: High-titer inhibitor threshold — >= 5 Bethesda units (BU)

High-titer inhibitor threshold>= 5 Bethesda units (BU)

ContextDefines patients as having high-titer factor VIII or IX inhibitors when Bethesda assay >= 5 BU.

Documentation requirementInhibitor titer (Bethesda units) must be documented for certain non-factor therapies and bypassing agents.

inv-34: Minimum age for several non-factor therapies — >= 12 years

Minimum age (common non-factor therapies)>= 12 years

Applies toAlhemo (concizumab), Hemlibra (emicizumab), Hympavzi (marstacimab), Fitusiran (Qfitlia) initial therapy criteria

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required and Member Plan Governance

Prior authorization is required for the listed non-factor and factor products when applicable to the member's benefit plan. Verify member-specific coverage and obtain prior authorization per the plan before initiating therapy.

Prior authorization requirements are governed by the member-specific benefit plan — inclusion of a code in this policy does not guarantee coverage.
Obtain prior authorization for J-codes listed in the Applicable Codes section when the member's plan requires it.
Coverage determinations must align with the member-specific benefit plan document and any applicable federal or state mandates.

Documentation Required

Documentation Requirements

Documentation in the medical record must clearly support the diagnosis and the specific indication for therapy. Include relevant diagnostic codes, assay results, prior treatment history, and clinical rationale.

Background and Evidence Highlights

Inherited bleeding disorders such as hemophilia A and B, von Willebrand disease, and congenital deficiencies of factors (e.g., Factor XIII, Factor X) are managed with replacement clotting factor concentrates or non‑factor hemostatic agents. Indications addressed in this policy include routine prophylaxis to prevent bleeding, peri‑operative management of surgical bleeding, and treatment of acute bleeding episodes. Products may be plasma‑derived or recombinant and have distinct FDA‑labeled indications and age/inhibitor constraints that must be met and documented for coverage consideration.

inv-21: Evidence-based coverage groups (trial-aligned) — included here to provide evidence alignment context

Clinical evidence supports coverage when prophylaxis or treatment matches studied populations and dosing regimens:

Trial-aligned evidence context: Summarized trial findings (emicizumab, Altuviiio, rFVIIIFc, rFIXFc, rebalancing agents) support coverage when patient age, inhibitor status, and dosing match the studied populations and regimens.

See individual product criteria for specific age and inhibitor-status requirements.

Key Definitions and Terms

inv-65: Congenital factor XIII deficiency — definition and product context

DefinitionCongenital factor XIII deficiency is an inherited deficiency of factor XIII (fibrin stabilizing factor) causing impaired fibrin cross-linking and bleeding tendency.

Product contextPlasma-derived factor XIII (Corifact) and recombinant FXIII A‑subunit (Tretten) are indicated for prophylaxis, peri-operative management, or treatment of bleeding episodes in congenital FXIII deficiency.

Prophylaxis regimen (rFXIII)Recombinant FXIII A‑subunit prophylaxis studied as 35 i.u./kg IV monthly (28 ±2 days) in phase 3 trial showing reduced bleeding rates.

inv-66: Von Willebrand disease (VWD) — definition and product context

DefinitionVon Willebrand disease (VWD) is a bleeding disorder treated with von Willebrand factor-containing concentrates and other hemostatic measures for prophylaxis, peri-operative management, or treatment of bleeding episodes.

Policy Revision History and Changes

2026-01-01policy_revisionLatest

Removed an administrative reference link in the Coverage Rationale and updated FDA and References sections to reflect current information; previous policy version IEXD0047.03 archived.

Policy Summary

PayerUnitedHealthcare

PolicyClotting Factors, Coagulant Blood Products, & Other Hemostatics

Policy CodePolicy IEXD0047.04

Change TypeOperational updates and reference revisions

Effective DateJan 1, 2026

Next Review Date

Key ActionObtain prior authorization demonstrating the covered diagnosis and intended treatment intent for listed branded clotting factor products.

SourceLink

On This Page

Diagnosis of hemophilia A without factor VIII inhibitors; patient is >=12 years; prescribed for routine prophylaxis

Hympavzi B initial: Diagnosis of hemophilia B without factor IX inhibitors; patient is >=12 years; prescribed for routine prophylaxis

Fitusiran initial: Diagnosis of hemophilia A OR B AND either: (A) no high-titer inhibitors AND (provider documents patient not appropriate candidate for Hympavzi OR patient currently on Qfitlia) OR (B) has developed high-titer inhibitors; patient is >=12 years; prescribed for routine prophylaxis

Continuation: For each agent: patient previously treated with the same agent; prescribed for prevention (routine prophylaxis); documentation of positive clinical response to therapy

Individualized (25-65 IU/kg every 3-5 days) or weekly (65 IU/kg) prophylaxis reduced ABR vs episodic treatment; extended half-life (19.0 h) allowed dosing 1-2 times/week for many subjects.

dosing per trial arms

no inhibitors developed in study

rFIXFc (Alprolix) evidence: Prophylaxis with rFIXFc (fixed or individualized intervals) reduced ABR by 83-87% vs episodic therapy; many bleeding episodes controlled with 1 dose and dosing intervals up to ~12.5 days were used.initial 50 IU/kg adjusted to trough 1-3% or 100 IU/kg every 10 days individualized

prolonged half-life supports 1-2 week intervals

Rebalancing agents (Alhemo, Hympavzi, Qfitlia) evidence: Concizumab, marstacimab, and fitusiran demonstrated large reductions in ABR vs no prophylaxis or on-demand therapy (Alhemo ~86% reduction; Hympavzi showed superiority vs on-demand and non-inferiority vs routine prophylaxis; fitusiran showed 71-73% reductions using antithrombin-based dosing).age ≥12 in most pivotal trials; antithrombin-based dosing required for fitusiran

warnings include thromboembolic events for some agents and dose adjustments based on antithrombin activity for fitusiran

Minor surgery/mucosal procedures:

For minor procedures, increase VWF activity to ≥ 0.50 IU/mL with desmopressin or factor concentrate plus tranexamic acid over raising VWF levels without tranexamic acid; for type 1 VWD with baseline VWF > 0.30 IU/mL and mild bleeding phenotype undergoing minor mucosal procedures, tranexamic acid alone is suggested over increasing VWF activity levels.

Heavy menstrual bleeding in women with VWD: Suggest hormonal therapy (combined hormonal contraception or levonorgestrel IUS) or tranexamic acid over desmopressin for women who do not wish to conceive; suggest tranexamic acid over desmopressin for women who wish to conceive.

Neuraxial anesthesia during labor: If neuraxial anesthesia is suitable, target VWF activity 0.50–1.50 IU/mL rather than > 1.50 IU/mL.0.50–1.50 IU/mL

Use in continuationContinuation criteria also require prior treatment with the same agent and documentation of response; age criterion applies to initial therapy.

inv-35: Minimum age for one product — >= 7 years

Minimum age (specific product)>= 7 years

Applies toJivi (antihemophilic factor, pegylated-aucl) — requires patient to be 7 years of age or older and previously treated with FVIII replacement therapy.

DocumentationPatient prior FVIII exposure must be documented per product criteria.

inv-36: rFXIII prophylaxis dose — 35 i.u./kg IV monthly (28 ±2 days)

Prophylaxis dosing (rFXIII)35 i.u./kg IV once monthly (every 28 ± 2 days)

IndicationProphylactic prevention of bleeding in congenital FXIII-A subunit deficiency as studied in phase 3 trial (patients ≥ 7 years included).

Clinical trial contextMonthly dosing for 52 weeks resulted in marked reduction in bleeding rate versus historic on-demand treatment.

inv-37: rFVIIa perioperative minimal effective dose — at least 13 μg/kg per single dose and no less than three administrations during maximum bleeding risk

rFVIIa perioperative minimal effective doseAt least 13 μg/kg per single dose and no less than three administrations during the period of maximum bleeding risk (day of operation)

Use caseCalculated from observational surgical registry data for congenital FVII deficiency perioperative management.

Safety noteLow effective doses were effective with no thromboses reported in the referenced follow-up period.

inv-38: Perioperative VWF/FVIII activity targets — Target both FVIII and VWF activity levels ≥ 0.50 IU/mL for at least 3 days after surgery; neuraxial anesthesia VWF target 0.50–1.50 IU/mL

Perioperative VWF/FVIII activity targetTarget both FVIII and VWF activity levels ≥ 0.50 IU/mL for at least 3 days after surgery

Neuraxial anesthesia targetFor neuraxial anesthesia in labor, target VWF activity 0.50–1.50 IU/mL

RationaleTargets based on professional society guidance and perioperative VWF/FVIII concentrate PK-guided dosing studies (e.g., Humate-P surgical study).

inv-39: Desmopressin trial threshold — Baseline VWF level < 0.30 IU/mL (primarily type 1 VWD)

Desmopressin trial thresholdBaseline VWF level < 0.30 IU/mL — suggest performing a desmopressin trial (primarily type 1 VWD)

Clinical applicationPerform a desmopressin trial and base treatment decisions on results rather than skipping to factor concentrate or tranexamic acid when desmopressin is a valid option.

PopulationPrimarily applies to patients with type 1 VWD for whom desmopressin is an appropriate option.

Document the diagnosis (e.g., hemophilia A/B, von Willebrand disease, congenital factor deficiencies) with appropriate ICD-10 codes.
Provide indication-specific documentation (e.g., prophylaxis vs treatment of bleeding episodes vs perioperative management).
Reference the member-specific benefit plan when submitting documentation to support medical necessity.

Documentation Required

Inhibitor Testing and Prior Therapy Documentation

For agents used when inhibitors are present (or absent), provide inhibitor testing and prior therapy documentation. Lack of required inhibitor assay documentation may result in denial or delay.

Include Bethesda inhibitor assay results and date of testing when inhibitors are part of the coverage criteria.
Document prior therapies (e.g., prior exposure to clotting factor concentrates, bypassing agents) and clinical response.
For initiation and continuation of several non‑factor therapies, provide inhibitor titer and prior therapy documentation as specified in the coverage criteria.

Prior Authorization

Qfitlia (fitusiran) Prior Authorization Considerations

Qfitlia (fitusiran) has specific authorization and dosing considerations: the approved regimen uses antithrombin‑based adjustable dosing — fixed monthly fixed‑dose regimens used in some trials are not approved due to thrombosis risk.

Document that the provider has determined the patient is not an appropriate candidate for Hympavzi when that is the basis for Qfitlia use, or document that the patient is currently on Qfitlia therapy.
If Qfitlia is requested, include prior treatment history, inhibitor status, and clinical rationale for choosing fitusiran over alternative agents.
Dosing must follow the approved antithrombin‑based adjustable regimen; fixed monthly dosing (as used in the randomized studies) is not an approved regimen and may increase thrombotic risk.

Documentation Required

Use of Another VWF‑Containing Product During a Bleeding Episode

When evaluating VWF-containing product use in clinical trials or when determining prior treatment failures, note conditions that constitute treatment non‑success.

A bleeding episode treated with another VWF‑containing product (excluding whole blood) may be considered non‑successful for the prior product.
Use of another VWF product during the same bleeding episode, requirement for transfusion, exceeding daily dosage limits, or prolonged duration beyond defined thresholds can affect determination of prior treatment failure.
Provide detailed documentation of prior VWF therapy, dates, doses, and response when relying on previous product trials to meet policy criteria.

Billing Rule

Coding and Billing Documentation

When prior authorization requests are submitted, include applicable procedure and diagnosis codes to support the request. The listing of codes in this policy is for reference and does not imply coverage.

Supply relevant HCPCS J‑codes and ICD‑10 diagnosis codes when requesting authorization (see Applicable Codes section).
The presence of a code in this policy does not guarantee coverage — verify benefits against the member‑specific plan.
UnitedHealthcare may use external tools (e.g., InterQual) in benefit administration; include clinical documentation to support any InterQual-based review.

Documentation Required

Perioperative Dosing and Hemostatic Response Documentation

Provide perioperative dosing and hemostatic response documentation when requesting coverage for surgical prophylaxis or management. Clinical trial perioperative dosing ranges and investigator‑reported hemostasis assessments may inform medical necessity determinations.

Include perioperative dosing regimen, timing of preoperative doses, and intraoperative/postoperative hemostatic assessments.
Report investigator/surgeon assessments of hemostasis (excellent/good/moderate/poor) or objective bleeding outcomes when available.
For members undergoing surgery, document target FVIII and VWF activity levels and duration of coverage requested in accordance with professional guidance.

Note

Evidence Supporting Routine Prophylaxis and Authorization Expectations

Clinical evidence supports routine prophylaxis over on‑demand treatment for many hemophilia indications. When seeking authorization for prophylaxis, provide prior bleeding history and justification for prophylactic therapy.

Include annualized bleeding rate (ABR), target joint history, prior on‑demand vs prophylaxis treatment history, and prior exposure days when applicable.
Be prepared to document prior dosing regimens, PK‑tailored therapy attempts, and reasons prophylaxis is indicated.
Requests to step up from on‑demand to routine prophylaxis should include clinical trial or real‑world data supporting reduced ABR in the individual patient.

Product contextVWF/FVIII concentrates (e.g., Humate-P, Alphanate, Wilate, Vonvendi) are used for peri-operative management and treatment; Humate-P dosing was PK-guided in surgical studies achieving effective hemostasis in most subjects.

Desmopressin roleDesmopressin trial is suggested for primarily type 1 VWD patients (baseline VWF < 0.30 IU/mL) before using concentrates where appropriate.

inv-67: High-titer inhibitors — Factor inhibitors >= 5 BU

High-titer inhibitors — definitionFactor inhibitors >= 5 Bethesda units (BU)

ImplicationPresence or absence of high-titer inhibitors is used to determine eligibility for several non-factor therapies and bypassing agents.

DocumentationBethesda inhibitor assay results must be provided where required by product criteria.

inv-68: Routine prophylaxis — definition

Routine prophylaxis — definitionPrescribed for the prevention of bleeding episodes (regular administration to reduce bleed frequency)

Context in policyNon-factor replacement therapies (Alhemo, Hemlibra, Hympavzi, Fitusiran) are proven and medically necessary for routine prophylaxis when specified criteria are met.

Continuation criteriaContinuation generally requires prior treatment with the same agent and documentation of a positive clinical response.

inv-69: Factor VIIa (rFVIIa) — definition and mechanism

DefinitionFactor VIIa (rFVIIa) is a vitamin K‑dependent glycoprotein that promotes hemostasis by forming complexes with tissue factor to activate factors X and IX, leading to thrombin generation and fibrin clot formation.

Clinical useUsed for peri-operative management and treatment of bleeding in congenital FVII deficiency, acquired hemophilia, and as a bypassing agent in inhibitors; minimal effective perioperative dosing described in registry data.

Perioperative dosing noteRegistry analysis identified minimally effective perioperative dosing of ≥13 μg/kg per single dose with at least three administrations during maximum bleeding risk.

inv-70: Recombinant Factor XIII (rFXIII, A-subunit) — definition and prophylactic use

DefinitionRecombinant Factor XIII (rFXIII, A‑subunit) is a recombinant human FXIII‑A homodimer that increases clot strength by cross‑linking fibrin and protecting clots from fibrinolysis.

Prophylactic useStudied and used prophylactically in congenital FXIII‑A deficiency at 35 i.u./kg IV monthly (28 ±2 days) to prevent bleeding episodes.

Clinical trial outcomePhase 3 study demonstrated marked reduction in bleeding rate versus historic on‑demand treatment with good tolerability.

inv-71: VWF/FVIII concentrates (Humate-P, Wilate) — definition and use in surgical/bleeding risk reduction

DefinitionVWF/FVIII concentrates (e.g., Humate-P, Wilate) are plasma‑derived products providing von Willebrand factor and factor VIII to reduce surgical and bleeding risk in VWD.

Use in perioperative carePK‑guided dosing in elective surgery (Humate‑P) achieved effective hemostasis in ~91% of subjects immediately after surgery.

IndicationsUsed for peri‑operative management, treatment of bleeding episodes, and, for some products, routine prophylaxis per FDA labeling and clinical criteria.

inv-72: Target joint — definition used to assess target joint bleeding

Target joint — definitionA joint with ≥ 3 spontaneous bleeding episodes in a major joint occurring in a consecutive 6‑month period (used to assess target joint bleeding and resolution).

Clinical relevanceResolution of target joints was used as an efficacy endpoint in prophylaxis trials (e.g., Altuviiio showed 100% target joint resolution in study subjects).

AssessmentTarget joint status supports prophylaxis decisions and evaluation of clinical response to therapy.

inv-73: Antithrombin-based dosing — definition for fitusiran dosing approach

Antithrombin‑based dosing — definitionAn adjustable dosing regimen for fitusiran (Qfitlia) in which dose adjustments are based on periodic measurements of antithrombin activity.

RationaleApproved because fixed‑dose regimens led to excessive clotting; efficacy established using antithrombin‑guided adjustments in extension studies.

Prior authorization implicationPA should confirm use of the approved antithrombin‑based dosing regimen and relevant clinical history (inhibitor status, prior on‑demand therapy).

inv-74: Bypassing agents — therapies used to treat bleeding in patients with inhibitors

DefinitionBypassing agents are therapies used to treat bleeding in patients with inhibitors by providing alternative pathways to generate thrombin (examples include recombinant factor VIIa [rFVIIa] and activated prothrombin complex concentrate [aPCC/FEIBA]).

Clinical roleUsed for on‑demand treatment of bleeds in patients with high‑titer inhibitors and as comparators in trials evaluating rebalancing agents and prophylaxis strategies.

DocumentationDocumentation of inhibitor status (e.g., Bethesda assay) is required when bypassing agents are indicated per product criteria.

inv-75: desmopressin (DDAVP) — definition and recommended trial use in type 1 VWD

Desmopressin (DDAVP) — definitionA pharmacologic agent suggested for trial in primarily type 1 VWD patients to raise VWF and FVIII levels; recommended to perform a trial when baseline VWF < 0.30 IU/mL.

Policy roleDesmopressin trial or documentation of failure/intolerance is required before some VWF‑containing concentrates for mild/moderate VWD per coverage criteria.

Alternative therapiesTranexamic acid or factor concentrates are alternatives when desmopressin is contraindicated or fails; professional guidance suggests tranexamic acid in certain settings for women with heavy menstrual bleeding.

inv-76: tranexamic acid — definition and role in VWD/heavy menstrual bleeding

Tranexamic acid — definitionAn antifibrinolytic agent used as adjunctive therapy in VWD and recommended over desmopressin for certain women with heavy menstrual bleeding; also suggested for minor procedures and postpartum periods.

Clinical rolesPreferred over desmopressin for women who wish to conceive and as adjunct to raise hemostasis in minor mucosal procedures or postpartum period per society guidance.

Combination useCan be used with desmopressin or factor concentrates for added hemostatic effect in perioperative or mucosal bleeding settings.