Medicare Advantage

Coagulation Factors
MA08.004r

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

HEMOPHILIA A (FACTOR VIII DEFICIENCY)
The following coagulation factors are considered medically necessary and, therefore, covered for the prevention and/or treatment of bleeding episodes in individuals with Hemophilia A (Factor VIII Deficiency):
  • human preparations: Alphanate®, Koate®DVI, Hemophil M, Humate-P®, and Wilate®
  • recombinant preparations: Advate®, Adynovate, Afstyla®, Eloctate®, Esperoct®, Jivi®, Kogenate FS®, Kovaltry®, Novoeight®, Nuwiq®, Recombinate®, and Xyntha®
  • human monoclonal antibody: Hemlibra®

HEMOPHILIA B (FACTOR IX DEFICIENCY)
The following coagulation factors are considered medically necessary and, therefore, covered for the prevention and/or treatment of bleeding episodes in individuals with Hemophilia B (Factor IX Deficiency):
  • human preparations: Alphanine® SD, Mononine®, and Profilnine® SD
  • recombinant preparations: Alprolix®, BeneFIX®, Idelvion®, Ixinity®, Rebinyn®, and Rixubis®

HEMOPHILIA C (FACTOR XI DEFICIENCY)
Factor XI concentrates are not currently available in the United States

HEMOPHILIA WITH INHIBITORS TO FACTORS VIII OR IX
The following coagulation factors are considered medically necessary and, therefore, covered for the prevention and/or treatment of bleeding episodes in individuals with hemophilia with inhibitors to factors VIII or IX:
  • human and recombinant factors VIII or IX (See Hemophilia A and B above)
  • FEIBA (human plasma-derived activated prothrombin complex concentrate [APCC])
  • recombinant activated coagulation factor VIIa (e.g., NovoSevenRT®, Sevenfact®)
  • human monoclonal antibody (e.g., emicizumab-kxwh [Hemlibra®]) for hemophilia with inhibitors to factor VIII

FACTOR I DEFICIENCY, CONGENITAL
Fibryga® and RiaSTAP® (fibrinogen concentrate [Human]) are considered medically necessary and, therefore, covered for the treatment of bleeding episodes in individuals with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. NOTE: See EXPERIMENTAL/INVESTIGATIONAL Section regarding dysfibrinogenemia.

FACTOR VII DEFICIENCY, CONGENITAL
NovoSevenRT® (recombinant-activated coagulation factor VIIa) is considered medically necessary and, therefore, covered for the prevention and/or treatment of bleeding episodes in individuals with congenital factor VII deficiency.

FACTOR VIII DEFICIENCY, ACQUIRED
The following coagulation factors are considered medically necessary and, therefore, covered for the prevention and/or treatment of bleeding episodes in individuals with acquired factor VIII deficiency:
  • Factor VIII concentrates, including Obizur
  • Alphanate® (antihemophilic factor VIII/von Willebrand factor complex [human])
  • NovoSevenRT® (recombinant-activated coagulation factor VIIa)
  • FEIBA (human plasma-derived activated prothrombin complex concentrate [APCC])

FACTOR X DEFICIENCY, ACQUIRED OR CONGENITAL
Coagadex® is considered medically necessary and, therefore, covered for the prevention and/or treatment of bleeding episodes in individuals with factor X deficiency, excluding the perioperative management of bleeding in individuals with severe hereditary Factor X deficiency.

FACTOR XIII DEFICIENCY, ACQUIRED OR CONGENITAL
The following coagulation factors are considered medically necessary and, therefore, covered for the prevention and/or treatment of bleeding episodes in individuals with acquired or congenital factor XIII deficiency:
  • Corifact® (Factor XIII Concentrate [Human])
  • Tretten® (Factor XIII A-Subunit [Recombinant]) 

GLANZMANN'S THROMBASTHENIA (GLYCOPROTEIN COMPLEX IIb/IIIa DEFICIENCY)
NovoSevenRT® (recombinant-activated coagulation factor VIIa) is considered medically necessary and, therefore, covered for the prevention and/or treatment of bleeding episodes in individuals with Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets.

VON WILLEBRAND DISEASE
The following coagulation factors are considered medically necessary and, therefore, covered for the prevention and/or treatment of bleeding episodes in individuals with von Willebrand disease when the use of desmopressin (1-desamino-8-D-arginine vasopressin [DDAVP]) is known or suspected to be ineffective or contraindicated:
  • human preparations: Alphanate®, Humate-P, Wilate®
  • recombinant preparation: Vonvendi

EXPERIMENTAL/INVESTIGATIONAL

In addition to indications that are not described above in the Medically Necessary Section, Fibryga® and RiaSTAP® are also considered experimental/investigational for the treatment of dysfibrinogenemia and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

All other uses for coagulation factors other than FDA labeled indications are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

NOT ELIGIBLE FOR REIMBURSEMENT

Bebulin, Helixate® FS, Hyate:C®, Monoclate-P®, NovoSeven®, and ReFacto® are no longer manufactured and have been withdrawn from market; therefore, they are not eligible for reimbursement.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.

BILLING REQUIREMENTS 

If there is no specific HCPCS code available for the drug administered, then the drug must be reported with the most appropriate unlisted code along with the corresponding National Drug Code (NDC).


Guidelines


This policy is consistent with Medicare's coverage determination for coagulation factors. The Company’s payment methodology may differ from Medicare.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, coagulation factors are covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

Certain drugs are available only through the member's medical benefit (Part B benefit), depending on how the drug is prescribed, dispensed, or administered. For Medicare Advantage members, coagulation factors​ are covered ONLY under a member's medical benefit (Part B benefit).

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

There are numerous drugs approved by the FDA for the prevention and treatment of bleeding due to a factor deficiency.


Description


Hemophilia and von Willebrand disease (VWD) are the most common congenital bleeding disorders. Bleeding disorders are a group of conditions that result when the blood cannot clot properly. In normal clotting, platelets stick together and form a plug at the site of vascular damage. Proteins in the blood called coagulation factors then interact in a series of physiological processes to form an insoluble fibrin clot that holds the platelets in place and allows healing to occur at the site of the injury while preventing blood from escaping the blood vessel. The coagulation factors are indicated by Roman numerals (e.g., VII, VIII, and IX).

HEMOPHILIA --- TYPES A, B, C

Hemophilia is a rare, typically inherited, bleeding disorder that can range from mild to severe, depending on how much clottin​​​g factor is present in the blood. Hemophilia A is considered the classic form of the disease, and is a consequence of a congenital deficiency of factor VIII. Hemophilia B, also called Christmas disease, is the result of a congenital deficiency of factor IX. Hemophilia C, a rare form of hemophilia, is the result of a congenital deficiency of factor XI. The defect results in the insufficient generation of thrombin by factor VIIIa, factor IX, or factor XI complex by means of the intrinsic pathway of the coagulation cascade. Individuals with less than 1 percent normal factor are considered to have severe hemophilia. Individuals with 1 percent to 5 percent normal factor are considered to have moderately severe hemophilia marked by spontaneous bleeding from the oral mucosa, joint bleeding, and bleeding from minor trauma. Individuals with more that 5 percent but less than 40 percent normal factor are considered to have mild hemophilia. Clinical bleeding symptom criteria have also been used for hemophilia classification when individuals have bleeding symptoms different than what would be expected from the plasma coagulant levels.

Because blood does not clot properly without enough clotting factor, any cut or injury carries the risk of excessive bleeding. The hallmark of congenital hemophilia is hemorrhage into the joints, or hemarthrosis. Synovial cells in joints synthesize high levels of tissue factor inhibitor, which predisposes hemophilic joints to bleed. This bleeding leads to progressive inflammation, deterioration, and deformities of the joint. In addition, people with hemophilia may suffer from internal bleeding that can damage organs and tissues over time.

TREATMENT
Treatment options include fresh frozen plasma and clotting factor products that are made from human blood products such as donated plasma, or synthetic (recombinant) products. The administration of antihemophilic factor products temporarily replaces the missing clotting factor to treat or prevent bleeding episodes. Human preparations are manufactured from human plasma obtained and screened from tested United States donors for use in the treatment of bleeding episodes. Improved screening techniques and specific viral-inactivation treatments have made these products safer. A major breakthrough has enabled scientists to create synthetic blood factors, called recombinants, in the laboratory by cloning the genes responsible for specific clotting factors. Today’s factor replacement therapies are much safer, reducing the risk of viral pathogens such as hepatitis B, hepatitis C, and HIV infection.

Hemophilia A (Factor VIII Deficiency)

Some examples of the human preparations of coagulation factor VIII for the treatment of hemophilia A include, Alphanate®, Koate®DVI, Hemophil M, Humate-P®, and Wilate®. Recombinant antihemophilic factor products for use in those with hemophilia A include Advate®, Adynovate, Afstyla®, Eloctate®, Esperoct®, Jivi®, Kogenate FS®, Kovaltry®, Novoeight®, Nuwiq®, Recombinate®, and Xyntha®. Additionally, Hemlibra® is an example of a humanized monoclonal antibody. These products have various US Food and Drug Administration (FDA)--labeled indications, depending on the specific product, which may include prevention and control of bleeding episodes; short-term routine prophylactic treatment to reduce or prevent spontaneous musculoskeletal bleeding episodes and the risk of joint damage; and/or prevention or control of bleeding in surgical procedures in certain individuals with hemophilia A.

Jivi® is not indicated for use in previously untreated individuals, and it also not indicated for use in children less than 12 years of age due to a greater risk for hypersensitivity reactions.

Hemophilia B (Factor IX Deficiency)

For the treatment of hemophilia B, human preparations of coagulation factor IX includes Alphanine® SD, Mononine®, and Profilnine® SD. Recombinant antihemophilic factor IX products include Alprolix®, BeneFIX®, Idelvion®, Ixinity®, Rebinyn®, Rixubis®. These products have various US Food and Drug Administration (FDA)--labeled indications, depending on the specific product, which may include the prevention or control of bleeding during surgical procedures. In addition to those indications, Alprolix® and Rixubis® also have an FDA approval for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in individuals with hemophilia B.

Hemophilia C (Factor XI Deficiency)

For the treatment of hemophilia C, replacement therapy via factor XI concentrates are not currently available in the United States.

HEMOPHILIA WITH INHIBITORS TO FACTORS VIII OR IX

Some individuals with severe forms of hemophilia A or hemophilia B develop autoantibody inhibitors that can neutralize factor VIII or factor IX, respectively. They neutralize the coagulant effects of replacement therapy. The levels of factor inhibitors are often measured by using the Bethesda method. The Bethesda method quantitates the inhibitor titer.

TREATMENT
Treatment of hemophilia with inhibitors to factors VIII or IX is complex and ranges from products that increase factor levels to factor-bypassing agents. Several different immune tolerance therapy regimens have been developed. For example, if attempts to lower antibody levels with immunosuppressants or corticosteroids have been unsuccessful, large doses of replacement factor VIII or factor IX can be used to try to produce inhibitor suppression, or eradication can be utilized. In addition, genetically engineered or recombinant antihemophilic factor VIII (e.g., Advate®, Kogenate FS®, Recombinate®) has the same biological effects as human factor VIII and has FDA approved indications for certain individuals with factor VIII inhibitor disorder with inhibitor titers less than 10 Bethesda units per milliliter.

Additionally, FEIBA is a human plasma-derived activated prothrombin complex concentrate (APCC) whose Factor VIII inhibitor bypassing activity controls spontaneous bleeding episodes and is also used during surgical interventions in individuals who have hemophilia A and hemophilia B with inhibitors. In December 2013, FEIBA received FDA approval for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B who have developed inhibitors.

Recombinant activated coagulation factor VIIa (e.g., NovoSevenRT®, Sevenfact®) has FDA labeled indications for use in the treatment of bleeding episodes or for the prevention or control of bleeding in surgical interventions and invasive procedures in certain individuals with hemophilia who have inhibitors to factor VIII or factor IX.

Emicizumab-kxwh (Hemlibra®) is a human monoclonal antibody that was approved by the FDA for the treatment of hemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors.

FACTOR I DEFICIENCY, CONGENITAL

Fibrinogen is a soluble protein in the bloodstream that is required to form clots. Fibrinogen is broken down to fibrin by the enzyme thrombin. Factor I (Fibrinogen) deficiency is a rare inherited bleeding disorder that is comprised of an absence of fibrinogen (afibrinogenemia), a low level of fibrinogen (hypofibrinogenemia), or fibrinogen of low quality that does not clot properly (dysfibrinogenemia).

TREATMENT
Management of acute hemorrhage include cryoprecipitate or fresh frozen plasma. Additionally, there are FDA-approved fibrinogen concentrates (Human), Fibryga® and RiaSTAP®, indicated for the treatment of acute bleeding episodes in individuals with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia. (NOTE: Fibryga® and RiaSTAP® are not indicated for dysfibrinogenemia.)

FACTOR VII DEFICIENCY, CONGENITAL

Factor VII is one of the vitamin K--dependent coagulation factors synthesized in the liver. Plasma factor VII predominately exists in an inactive form; however, approximately one percent circulates in the activated form as factor VIIa. In response to injury or inflammation, factor VIIa activates other clotting factors, initiating the coagulation cascade. Congenital factor VII deficiency is a rare hemorrhagic disorder. The severity of the bleeding manifestations in affected individuals varies from mild to severe.

TREATMENT
Management of acute hemorrhage primarily consists of administration of factor VII to treat bleeding episodes. Due to the short half-life of factor VII, a treatment alternative may include recombinant-activated coagulation factor VIIa (NovoSevenRT®), which is similar to human plasma--derived factor VIIa, with FDA labeled indications that include the treatment of bleeding episodes and the prevention or control of bleeding in surgical interventions or invasive procedures in certain individuals who have a factor VII deficiency. The need for prophylaxis is determined by the individual's clinical presentation and the number of clinically significant bleeding episodes requiring intervention.

FACTOR VIII DEFICIENCY, ACQUIRED

Acquired hemophilia A is the development of factor VIII inhibitors (autoantibodies) in persons without a history of factor VIII deficiency. It develops with a frequency of one case per one million population per year. Though the disorder is rare, it is known to cause significant morbidity and mortality. It may be associated with other disease conditions (e.g., collagen vascular disease, drug reaction, lymphoproliferative malignancies), or it can be idiopathic.

TREATMENT
Early treatment is directed toward achieving hemostasis and inhibitor eradication. Appropriate options for the treatment of bleeding episodes or for the prevention or control of bleeding in surgical procedures will depend on clinical presentation, and may include the use of immunosuppressive agents, desmopressin (1-desamino-8-D-arginine vasopressin [DDAVP]), Obizur and other factor VIII concentrates, antihemophilic factor VIII/von Willebrand factor complex (human) (Alphanate®), recombinant-activated coagulation factor VIIa (NovoSevenRT®) or FEIBA.

FACTOR VIII DEFICIENCY, CONGENITAL

See HEMOPHILIA A section (above).

FACTOR IX DEFICIENCY

See HEMOPHILIA B section (above).

FACTOR X DEFICIENCY, ACQUIRED OR CONGENITAL

Factor X is a vitamin K–dependent factor that is the first step in the common pathway to thrombus formation. Factor X can be activated by either the intrinsic or extrinsic clotting cascades. Factor X clotting deficiency may be acquired or congenital.

TREATMENT
Treatment options include fresh frozen plasma or plasma-derived prothrombin complex concentrates (plasma products containing a combination of vitamin K-dependent proteins) to stop or prevent bleeding. Additionally, Coagadex® is the first human factor X concentrate approved by the FDA for the treatment of hereditary factor X deficiency. It is indicated for routine prophylaxis to reduce the frequency of bleeding episodes, on-demand treatment and control of bleeding episodes, and for perioperative (period extending from the time of hospitalization for surgery to the time of discharge) management of bleeding in patients with mild and moderate hereditary Factor X deficiency.

FACTOR XI DEFICIENCY, ACQUIRED OR CONGENITAL

See HEMOPHILIA C section (above).

FACTOR XIII DEFICIENCY

ACQUIRED FACTOR XIII DEFICIENCY
Acquired factor XIII deficiency has been described in association with a variety of diseases such as hepatic failure, inflammatory bowel disease, and myeloid leukemia. Deficiency of factor XIII can be corrected with infusions of fresh frozen plasma, cryoprecipitate, or factor XIII concentrates.

CONGENITAL FACTOR XIII DEFICIENCY
Factor XIII is the protein responsible for stabilizing the formation of a blood clot. Congenital factor XIII deficiency is known as fibrin-stabilizing factor deficiency. In the absence of factor XIII, a clot will still develop, but it will remain unstable. This condition, a rare autosomal disease, is perhaps the rarest of all factor deficiencies. It is a potentially life-threatening bleeding disorder in which the blood clots normally but the clots formed are unstable, leading to recurrent bleeding. It is estimated that the condition affects one in every three million to five million births. It affects men and women equally. Most individuals with factor XIII deficiency experience symptoms from birth, often bleeding from the umbilical cord stump. Symptoms such as menorrhagia, bleeding in soft tissue, abnormal bleeding during or after injury or surgery, and hemarthrosis tend to continue throughout life but may be managed prophylactically.

Treatment

Treatment options for factor XIII deficiency include cryoprecipitate or fresh frozen plasma, which are made from human blood products such as donated plasma. In February 2011, Factor XIII Concentrate (Human) (Corifact®) was approved by the FDA for routine prophylactic treatment of congenital factor XIII deficiency and was later indicated for the peri-operative management of surgical bleeding in adult and pediatric patients with congenital factor XIII deficiency. Corifact® received orphan drug designation by the FDA because it is intended for use in a rare disease or condition. It was approved for marketing under the FDA's accelerated approval regulations. Additionally, in December 2013, the FDA approved the first recombinant product, Tretten®, for use in the routine prevention of bleeding in those who have congenital Factor XIII A-subunit deficiency.

GLYCOPROTEIN COMPLEX IIb/IIIa DEFICIENCY

Glanzmann’s thrombasthenia is a rare inherited bleeding disorder caused by an abnormality in the glycoprotein complex IIb/IIIa. This disorder prevents platelets from initiating clot formation.

TREATMENT
Treatment options for Glanzmann’s thrombasthenia include blood platelet transfusions and recombinant-activated coagulation factor VIIa (NovoSevenRT®). NovoSevenRT® was approved by the FDA for the treatment of bleeding episodes and peri-operative management in adults and children with Glanzmann’s thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets.

VON WILLEBRAND DISEASE (VWD)

Von Willebrand disease (VWD) is a congenital condition that results when there is an abnormality, either quantitative or qualitative, of von Willebrand factor. von Willebrand factor is required for normal platelet adhesion: it functions in both primary (involving platelet adhesion) and secondary (involving factor VIII) hemostasis. In primary hemostasis, von Willebrand factor attaches onto the platelet surface and acts as an adhesive bridge between the platelets and the damaged subendothelium at the site of vascular injury. In secondary hemostasis, von Willebrand factor protects factor VIII from degradation and delivers it to the site of injury. Bleeding tendency is usually mild and is characterized by a tendency for easy bruising, frequent epistaxis, and menorrhagia. VWD is classified into three different types (Types 1, 2, and 3), based on the levels of von Willebrand factor and factor VIII activity in the blood. Type 1 is the mildest and most common form; Type 3 is the most severe and least common form.

TREATMENT
Desmopressin (1-desamino-8-D-arginine vasopressin [DDAVP]) is a synthetic vasopressin analogue that has become a mainstay of therapy for most individuals with mild VWD. At appropriate doses, desmopressin causes a two-fold to five-fold increase in plasma von Willebrand factor and factor VIII concentrations in individuals who are healthy and responsive. Desmopressin can be used to treat bleeding complications or to prepare individuals with VWD for surgery. In a subtype of VWD (type IIB), desmopressin may cause a paradoxical drop in the platelet count and should not be used in a therapeutic setting without prior testing to see how the individual responds.

The goal of therapy is to correct the defect in platelet adhesiveness (by raising the level of effective von Willebrand factor) and to correct the defect in blood coagulation (by raising the level of factor VIII). Products such as von Willebrand factor/coagulation factor VIII complex (human) (Wilate®) and antihemophilic factor/von Willebrand factor complexes (human) (Alphanate® and Humate-P) are developed from human plasma consisting of two different proteins (factor VIII and von Willebrand factor).

Wilate® has been FDA approved for the treatment of spontaneous or trauma induced bleeding episodes in certain individuals with severe VWD, as well as individuals with mild or moderate VWD in whom desmopressin is known or suspected to be ineffective or contraindicated. This product is also indicated for the perioperative management of bleeding.

Alphanate® has been FDA approved for surgical and/or invasive procedures in individuals with VWD in whom desmopressin (DDAVP) is either ineffective or contraindicated. This product is not indicated for individuals with severe VWD (Type 3) undergoing major surgery.

Humate-P® has been approved by the FDA for the treatment of spontaneous and trauma-induced bleeding episodes and for the prevention of excessive bleeding related to surgery in adult and pediatric individuals with VWD. The FDA has also approved Humate-P® in individuals with mild and moderate VWD for whom desmopressin is known or suspected to be ineffective. In addition, Humate-P® is the first product specifically FDA approved for individuals with severe VWD who are undergoing major surgery.

Additionally, a synthetic (recombinant) product, Vonvendi, has been FDA approved for the on-demand treatment and control of bleeding episodes in adults diagnosed with von Willebrand disease. This product was later approved for the perioperative management of bleeding.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.


References


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Esperoct (Antihemophilic factor, recombinant, glycopegylated-exei). Prescribing information & supplemental biologics license approval letter. Approved 02/19/2019. Updated 10/2019. Available at: https://www.esperoct.com/ . Accessed June 10, 2020.

FEIBA (Anti-Inhibitor Coagulant Complex). Prescribing information. 02/2020. Baxter Healthcare Corporation. Lexington, MA. Available at: www.feiba.com. Accessed June 5, 2020.

Fibryga®. Fibrinogen (Human). Prescribing information. 07/2017. Octapharma USA, Inc. Hoboken, NJ. Available at: https://www.fibrygausa.com/#hcp. Accessed June 18, 2020.

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Hemlibra®. emicizumab-kxwh. Prescribing information. 10/2018. Genentech, Inc.; San Francisco, CA. Available at: https://www.hemlibra.com/ . Accessed June 8, 2020.

Hemophil M (Antihemophilic Factor [Human] Factor VIII). Lexington, MA: Baxalta US Inc. Prescribing information. 06/2018. Available at: https://www.takeda.com/en-us/what-we-do/product-portfolio/#section-h . Accessed June 15, 2020.

Hoffman M. Recombinant factor VIIa: Clinical uses, dosing, and adverse effects. [UpToDate Web site]. 03/19/19. Available at:
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Hoots WK, Shapiro AD. Factor VIII and factor IX inhibitors in patients with hemophilia. 04/06/2020. [UpToDate Web Site]. Available at [via subscription only]: http://www.uptodate.com/contents/factor-viii-and-factor-ix-inhibitors-in-patients-with-hemophilia. Accessed June 22, 2020.

Hoots WK, Shapiro AD. Treatment of bleeding and perioperative management in hemophilia A and B. 11/26/18. [UpToDate Web Site]. Available at [via subscription only]: http://www.uptodate.com/contents/treatment-of-hemophilia?source=see_link&sectionName=Factor+VIII+products&anchor=H11#H11. Accessed June 22, 2020.

Humate-P®. Antihemophilic factor/von Willebrand factor complex [human]. [package insert]. CSL Behring LLC Kankakee, IL.; 09/2017. Available at: http://www.humate-p.com/. Accessed June 18, 2020.

Idelvion®. Coagulation factor IX (recombinant). Prescribing information. 10/2019. CSL Behring LLC Kankakee, IL. Available at: http://www.idelvion.com/ . Accessed June 15, 2020.

Ixinity. Coagulation Factor IX (Recombinant). Prescribing information. 12/2018. Aptevo BioTherapeutics LLC: Berwyn, PA. Available at: https://www.ixinity.com/ . Accessed June 18, 2020.

Jivi®. Antihemophilic factor (recombinant) PEGylated-aucl. Prescribing information. 08/2018. Bayer Healthcare LLC: Whippany, NJ. Available at: https://www.jivi-us.com/ . Accessed June 15, 2020.

Koate® DVI. Antihemophilic Factor (Human), Factor VIII. Prescribing information. 08/2012. Grifols Therapeutics Inc. Research Triangle Park, NC. Available at: http://www.koate-dvi.com/en/web/koate-dvi . Accessed June 15, 2020.

Kogenate FS®. Antihemophilic factor (recombinant). Prescribing information. 12/2019. Available at: https://www.kogenatefs.com/home/prescribing-information . Accessed June 15, 2020.

Kovaltry®. Antihemophilic factor (recombinant). Prescribing information. 03/2016. Available at: https://www.kovaltry-us.com/. Accessed June 15, 2020.

Lexi-Drugs Compendium. 2020. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed June 22, 2020.

Lusher JM. Hemophilia: from plasma to recombinant factors. [American Society of Hematology Web site]. 12/2008. Web Site no longer active.

Ma AD, Carrizosa D. Acquired factor VIII inhibitors: pathophysiology and treatment. Hematology Am Soc Hematol Educ Program. 2006:432-7.

Mannucci PM. Rare inherited coagulation disorders. 02/05/2020. [UpToDate Web site]. Available at: http://www.uptodate.com/contents/rare-recessively-inherited-coagulation-disorders?source=search_result&search=Rare+(recessively+inherited)+coagulation+disorders&selectedTitle=2~150 [via subscription only]. Accessed June 18, 2020.

Monoclate-P. Discontinued Product via Lexi-Drugs. Site Updated 04/30/2020. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/6364?cesid=7gHDkVkVKfv&searchUrl=/lco/action/search?q=monoclate-p&t=name&va=monoclate-p# . Accessed June 15, 2020.

Mononine®. Coagulation Factor IX (Human). Prescribing information. 12/2018. CSL Behring LLC Kankakee, IL. Available at: http://www.cslbehring-us.com/products/Mononine.htm . Accessed June 18, 2020.

NovoSeven®. Discontinued Product via Lexi-Drugs. Site Updated 05/29/2020. Available at: http://online.lexi.com/lco/action/search?q=novoseven&t=name&va=novoseven . Accessed June 23, 2020.

NovoSevenRT®. Coagulation factor VIIa (recombinant). Prescribing information. 01/2019. Novo Nordisk Inc. Plainsboro, NJ. Available at: http://www.novosevenrt.com/. Accessed June 22, 2020.

National Hemophilia Foundation (NHF). Medical and Scientific Advisory Council (MASAC) recommendations concerning products licensed for the treatment of hemophilia and other bleeding disorders. [NHF Web site]. 03/16/2020. Available at: http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=57&contentid=693. Accessed June 22, 2020.

National Hemophilia Foundation (NHF). Types of bleeding disorders. [NHF Web site]. 2020. Available at: https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders. Accessed June 18, 2020.

National Organization of Rare Diseases (NORD). Acquired hemophilia. Updated 2016. Available at: https://rarediseases.org/rare-diseases/acquired-hemophilia/ . Accessed June 5, 2020.

Novitas Solutions, Inc. Local Coverage Article: Billing and Coding: Hemophilia Factor Products (A56433) [Novitas Solutions, Inc. Medicare Services Web site]. Original: 04/25/2019. Revised: 07/01/2020. Available at: https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=56433&ver=36&name=331*1&UpdatePeriod=843&bc=AAAAEAAAAAAA&. Accessed July 31, 2020.

Novitas Solutions, Inc. Local Coverage determination (LCD). LCD L35111: Hemophilia Factor Products. [Novitas Solutions, Inc. Medicare Services Web site]. Original: 10/01/2015. Revised: 02/13/2020. Available at:
https://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=35111&ver=76&articleId=54117&name=331*1&UpdatePeriod=872&bc=AAAACAAAAAAA& . Accessed June 5, 2020.

Novoeight®. Coagulation factor VIII (recombinant). Prescribing information. 11/2018. Novo Nordisk Inc: Plainsboro, NJ. Available at: https://www.novoeight.com/ . Accessed June 15, 2020.

Nuwiq®. Coagulation factor VIII (recombinant). Prescribing information. 07/2017. Octapharma USA Inc: Hoboken, NJ. Available at: http://www.nuwiqusa.com/ . Accessed June 15, 2020.

Obizur. Antihemophilic Factor (Recombinant), Porcine sequence. Prescribing information. 01/2020. Lexington, MA: Baxalta US Inc. Available at: http://www.obizur.com/ . Accessed June 15, 2020.

Peyvandi F. Epidemiology and treatment of congenital fibrinogen deficiency. Thromb Res. 2012 Dec;130 Suppl 2:S7-11.

Profilnine® SD. Coagulation factor IX complex (human). Prescribing information. 06/2018. Grifols Biologicals Inc: Los Angeles, CA. Available at: https://www.grifols.com/en/product/-/product/united-states/profilnine . Accessed June 18, 2020.

Rebinyn®. Coagulation factor IX (recombinant) GlycoPEGylated). Prescribing information. 05/2017. Novo Nordisk Inc. Plainsboro, NJ. Available at: https://www.rebinyn.com/ . Accessed June 18, 2020.

RECOMBINATE®. Antihemophilic factor, recombinant. Prescribing information. 06/2018. Lexington, MA: Baxalta US Inc. Available at: http://www.recombinate.com/ . Accessed June 15, 2020.

Refacto®. Antihemophilic factor, recombinant. Discontinued Product via Lexi-Drugs and Clinical Pharmacology. Available at: http://online.lexi.com/lco/action/search?q=refacto&t=name&va=refacto and https://www.clinicalkey.com/pharmacology/monograph/40?sec=monsup&n=ReFacto . Accessed June 15, 2020.

RiaSTAP®. [Package Insert]. Labeling revised 01/2020. Kankakee, IL: CSL Behring LLC. Available at: http://www.riastap.com/. Accessed June 18, 2020.

Rixubis®. Coagulation Factor IX (Recombinant). Prescribing information. 12/2019. Baxter US Inc: Lexington, MA. Available at: https://www.rixubis.com/ . Accessed June, 18, 2020.

Roberts HR, Hoffman M. Hemophilia A and hemophilia B. In: Butler E, Coller BS, Lichtman MA, Kipps TJ, Seligsohn U, eds. Hematology.6th ed. New York, NY: McGraw-Hill; 2001: 1639-1657.

Rudisill CN, Hockman RH, Degregory KA, et al. Implementing guidelines for the institutional use of factor VIIa (recombinant): a multidisciplinary solution. Am J Health-System Pharmacy.2006;63(17): 1641-1646.

Schwartz RA. Factor IX Deficiency (Hemophilia B) Medication. [eMedicine Web site]. 06/09/2020. Available at: http://emedicine.medscape.com/article/199088-medication#showall. Accessed June 22, 2020.

Schwartz RA. Factor X Deficiency. [eMedicine Web site]. 02/18/2020. Available at: http://emedicine.medscape.com/article/209867-overview. Accessed June 18, 2020.

Schwartz RA. Factor XIII Deficiency Treatment & Management. [eMedicine Web site]. 06/09/2020. Available at: http://emedicine.medscape.com/article/209179-treatment. Accessed June 22, 2020.

Tahlan A, Ahluwalia J. Factor XIII: congenital deficiency factor XIII, acquired deficiency, factor XIII A-subunit, and factor XIII B-subunit. Arch Pathol Lab Med. 2014 Feb;138(2):278-81.

Tretten®. Coagulation Factor XIII A-Subunit (Recombinant). Prescribing information. 11/2016. Novo Nordisk Inc. Plainsboro, NJ. Available at: http://www.tretten.com/ . Accessed June 18, 2020.

Truven Health Analytics Inc. Micromedex® 2.0. DrugDex. Antihemophilic Factor (various). [Micromedex Web site]. 2019. Available at: http://www.micromedexsolutions.com/micromedex2/librarian/ [via subscription only]. Accessed June 22, 2020.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Antihemophilic factor/von Willebrand factor complex (human). Alphanate®. Prescribing information for acquired Factor VIII deficiency. [FDA Web site]. Available at: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/alphanate . Accessed June 16, 2020.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Coagulation factor VIIa (recombinant)-jncw (Sevenfact®). Package insert & supplemental biologics license approval letter. [FDA Web site]. Louisville, KY: HEMA Biologics, LLC. Available at: https://www.fda.gov/vaccines-blood-biologics/sevenfact . Accessed June 5, 2020.

Vonvendi. von Willebrand Factor (Recombinant). Prescribing information. 02/2019. Baxalta US Inc: Lexington, MA.
Available at: http://www.vonvendi.com/ . Accessed June 18, 2020.

Wilate®. von Willebrand factor/coagulation factor VIII complex [human]). Prescribing information. 09/2019. Octapharma USA, Inc.: Hoboken, NJ. Available at: https://www.wilateusa.com/ . Accessed June 5, 2020.

Wilczynski C. Fibrinogen. [eMedicine Web site]. 11/21/2019. Available at: http://emedicine.medscape.com/article/2085501-overview#showall . Accessed June 18, 2020.

XYNTHA®. Antihemophilic factor (recombinant), plasma/albumin free. Product information. 08/2019. Available at: https://www.xyntha.com/ . Accessed June 15, 2020.

Zaiden RA. Hemophilia B. 06/08/17. Available at: http://emedicine.medscape.com/article/779434-overview. Accessed July 22, 2019.



Coding

CPT Procedure Code Number(s)
N/A

ICD - 10 Procedure Code Number(s)
N/A

ICD - 10 Diagnosis Code Number(s)

D66 Hereditary factor VIII deficiency

D67 Hereditary factor IX deficiency

D68.0 Von Willebrand's disease

D68.2 Hereditary deficiency of other clotting factors

D68.311 Acquired hemophilia

D68.312 Antiphospholipid antibody with hemorrhagic disorder

D68.318 Other hemorrhagic disorder due to intrinsic circulating anticoagulants, antibodies, or inhibitors

D68.4 Acquired coagulation factor deficiency

D69.1 Qualitative platelet defects

HCPCS Level II Code Number(s)

MEDICALLY NECESSARY

J7170 Injection, emicizumab-kxwh, 0.5 mg

J7177 Injection, human fibrinogen concentrate (fibryga), 1 mg

J7179 Injection, von Willebrand factor (recombinant), (Vonvendi), 1 IU VWF:RCo

J7182 Injection, factor VIII, (antihemophilic factor, recombinant), (NovoEight), per IU

J7183 Injection, von Willebrand factor complex (human), Wilate, 1 IU vWF:RCo

J7185 Injection, factor VIII (antihemophilic factor, recombinant) (Xyntha), per IU

J7187 Injection, von Willebrand factor complex (Humate-P), per IU VWF:RCO

J7189 Factor viia (antihemophilic factor, recombinant), (novoseven rt), 1 microgram

J7200 Injection, factor IX, (antihemophilic factor, recombinant), Rixubis, per IU

J7201 Injection, factor IX, Fc fusion protein, (recombinant), Alprolix, 1 IU

J7202 Injection, factor IX, albumin fusion protein, (recombinant), Idelvion, 1 IU

J7203 Injection factor ix, (antihemophilic factor, recombinant), glycopegylated, (rebinyn), 1 iu

J7204 Injection, factor viii, antihemophilic factor (recombinant), (esperoct), glycopegylated-exei, per iu

J7208 Injection, factor viii, (antihemophilic factor, recombinant), pegylated-aucl, (jivi), 1 i.u.

J7209 Injection, factor VIII, (antihemophilic factor, recombinant), (Nuwiq), 1 IU

J7210 Injection, factor viii, (antihemophilic factor, recombinant), (Afstyla), 1 I.U.

J7211 Injection, factor viii, (antihemophilic factor, recombinant), (Kovaltry), 1 I.U.

J7212 Factor viia (antihemophilic factor, recombinant)-jncw (sevenfact), 1 microgram


THE FOLLOWING CODE IS USED TO REPRESENT Coagadex®:

J7175 Injection, factor X, (human), 1 IU


THE FOLLOWING CODE IS USED TO REPRESENT RiaSTAP®:

J7178 Injection, human fibrinogen concentrate, not otherwise specified, 1 mg


THE FOLLOWING CODE IS USED TO REPRESENT Corifact®:

J7180 Injection, factor XIII (antihemophilic factor, human), 1 IU


THE FOLLOWING CODE IS USED TO REPRESENT Tretten®:

J7181 Injection, factor XIII A-subunit, (recombinant), per IU


THE FOLLOWING CODE IS USED TO REPRESENT Alphanate®:

J7186 Injection, antihemophilic factor VIII/von Willebrand factor complex (human), per factor VIII i.u.


THE FOLLOWING CODE IS USED TO REPRESENT Obizur:

J7188 Injection, factor VIII (antihemophilic factor, recombinant), per IU


THE FOLLOWING CODE IS USED TO REPRESENT Koate®DVI and  Hemophil M:

J7190 Factor VIII (antihemophilic factor, human) per IU


THE FOLLOWING CODE IS USED TO REPRESENT Advate®, Kogenate FS®, and Recombinate®:

J7192 Factor VIII (antihemophilic factor, recombinant) per IU, not otherwise specified


THE FOLLOWING CODE IS USED TO REPRESENT Alphanine® SD, Mononine®:

J7193 Factor IX (antihemophilic factor, purified, nonrecombinant) per IU


THE FOLLOWING CODE IS USED TO REPRESENT Profilnine® SD:

J7194 Factor IX complex, per IU


THE FOLLOWING CODE IS USED TO REPRESENT BeneFIX®, Ixinity®:

J7195 Injection, factor IX (antihemophilic factor, recombinant) per IU, not otherwise specified


THE FOLLOWING CODE IS USED TO REPRESENT FEIBA (human plasma-derived activated prothrombin complex concentrate [APCC]):

J7198 Antiinhibitor, per IU


THE FOLLOWING CODE IS USED TO REPRESENT Eloctate®:

J7205 Injection, factor VIII Fc fusion protein (recombinant), per IU


THE FOLLOWING CODE IS USED TO REPRESENT Adynovate:

J7207 Injection, factor VIII, (antihemophilic factor, recombinant), PEGylated, 1 IU


NOT ELIGIBLE FOR REIMBURSEMENT
 

THE FOLLOWING CODES REPRESENT BEBULIN, HELIXATE® FS, HYATE:C®, MONOCLATE-P®, NOVOSEVEN® , AND REFACTO® WHICH ARE NO LONGER MANUFACTURED AND HAVE BEEN WITHDRAWN FROM THE MARKET: 

J7189 Factor VIIa (atihemophilic factor, recombinant), per 1 mcg 

J7190 Factor VIII (antihemophilic factor, human) per IU 

J7191 Factor VIII (antihemophilic factor (porcine), per IU 

J7192 Factor VIII (antihemophilic factor, recombinant) per IU, not otherwise specified 

J7194 Factor IX complex, per IU




Revenue Code Number(s)
N/A

Modifiers


N/A

Coding and Billing Requirements


BILLING REQUIREMENTS

If there is no specific HCPCS code available for the drug administered, then the drug must be reported with the most appropriate unlisted code along with the corresponding National Drug Code (NDC).


Policy History

1/1/2021
1/1/2021
MA08.004
Medical Policy Bulletin
Medicare Advantage
No