This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

This policy refers to the following clotting factors and coagulant blood products:

Congenital Factor VII Deficiency

Factor VIIa (recombinant) [NovoSeven RT] may be considered medically necessary in adult or pediatric individuals when ALL of the following criteria are met:

• Diagnosis of congenital factor VII deficiency; and
• At least ONE of the following:
• Treatment of acute bleeding episode; or
• Prevention of bleeding in surgical interventions or invasive procedures (i.e., surgical prophylaxis).

Glanzmann Thrombasthenia

Factor VIIa (recombinant) [NovoSeven RT] may be considered medically necessary in adult and pediatric individuals as an alternative to platelet transfusions when ALL of the following criteria are met:

• Diagnosis of Glanzmann’s thrombasthenia; and
• At least ONE of the following:
• Treatment of a bleeding episode; or
• Prevention of bleeding in surgical interventions or invasive procedures (i.e., surgical prophylaxis).

All indications not mentioned within this policy are considered experimental/investigational and therefore non-covered. The scientific evidence has not established the safety and efficacy for use in other indications.

Congenital Factor XIII Deficiency (i.e., Fibrin Stabilizing Factor Deficiency)

Factor XIII (plasma-derived) [Corifact] may be considered medically necessary in adult and pediatric individuals when ALL of the following criteria are met:

• Diagnosis of congenital factor XIII deficiency; and
• At least ONE of the following:
• Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes; or
• Peri-operative management of surgical bleeding; or
• Treatment of acute bleeding episode.

Coagulation Factor XIII A-subunit (recombinant) [Tretten] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of congenital factor XIII A-subunit deficiency; and
• At least ONE of the following:
• Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes; or
• Peri-operative management of surgical bleeding; or
• Treatment of acute bleeding episode.

All indications not mentioned within this policy are considered experimental/investigational and therefore non-covered. The scientific evidence has not established the safety and efficacy for use in other indications.

Fibrinogen Deficiency (i.e., Factor I deficiency)

Fibrinogen Concentrate (plasma-derived) [RiaSTAP] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia; and
• Treatment of acute bleeding episode.

All indications not mentioned within this policy are considered experimental/investigational and therefore non-covered. The scientific evidence has not established the safety and efficacy for use in other indications.

Hereditary Factory X deficiency

Factor X (plasma-derived) [Coagadex] may be considered medically necessary in individuals greater than or equal to 12 years of age when ALL of the following criteria are met:

• Diagnosis of hereditary factor X deficiency; and
• At least ONE of the following:
• On-demand treatment and control of bleeding episodes or
• Peri-operative management of surgical bleeding in patients with mild hereditary Factor X deficiency.

All indications not mentioned within this policy are considered experimental/investigational and therefore non-covered. The scientific evidence has not established the safety and efficacy for use in other indications.

Hemophilia A (i.e., Congenital Factor VIII Deficiency, Factor VIII Deficiency, Classical Hemophilia)

Factor VIII (plasma-derived)/von Willebrand Factor (vWF) complex (plasma-derived) [Alphanate or Humate-P], Factor VIII (plasma-derived) [Hemofil M, Koāte-DVI or Monoclate-P), Factor VIII (recombinant) [Advate, Helixate FS, Kogenate FS, Novoeight, Recombinate, or Xyntha, Xyntha Solofuse], may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of hemophilia A; and
• At least ONE of the following:
• Treatment of acute bleeding episode; or
• Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes; or
• Prevention of bleeding in surgical interventions or invasive procedures (e.g., surgical prophylaxis).

Antihemophilic factor (recombinant) [Adynovate, Afstyla, Eloctate, Kovaltry, Nuwiq] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of hemophilia A; and
• At least ONE of the following:
• Treatment of acute bleeding episode; or
• Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes; or
• Prevention of bleeding in surgical interventions or invasive procedures (e.g., surgical prophylaxis).

Anti-inhibitor coagulant complex (plasma-derived) [Feiba NF, Feiba VH] and factor VIIa (recombinant) [NovoSeven RT] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of hemophilia A; and
• Documentation of inhibitors (e.g., Bethesda inhibitor assay); and
• At least ONE of the following:
• Treatment of bleeding episodes; or
• Routine prophylactic treatment of severe status less than 1% of normal factor (less than 0.01 IU/ml); or
• Prophylactic therapy of documented history of one (1) or more episodes of spontaneous bleeding into joints; or
• Prevention of bleeding in surgical interventions (i.e., surgical prophylaxis).

Humanized monoclonal antibody emicizumab-kxwh (Hemlibra) may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of hemophilia A; and
• Documentation of inhibitors (e.g., Bethesda inhibitor assay); and
• At least ONE of the following:
• Routine prophylactic treatment of severe status less than 1% of normal factor (less than 0.01 IU/ml); or
• Prophylactic therapy of documented history of one (1) or more episodes of spontaneous bleeding into joints.

Factor VIII (plasma-derived) / vWF complex (plasma-derived) [Alphanate] and factor VIIa (recombinant) [NovoSeven RT] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of acquired factor VIII hemophilia (e.g., acquired hemophilia A, factor VIII deficiency); and
• At least ONE of the following:
• Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes; or
• Treatment of acute bleeding episode.

Antihemophilic factor (recombinant), porcine sequence [Obizur] may be considered medically necessary in adults when ALL of the following criteria are met:

• Diagnosis of acquired factor VIII hemophilia (e.g., acquired hemophilia A, acquired hemophilia Factor VIII deficiency); and
• Baseline anti-porcine factor VIII inhibitor titer less than 20 BU; and
• Treatment of acute bleeding episode.

Tranexamic acid [Cyklokapron] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of hemophilia A; and
• Prevention of hemorrhage and reduction of the need for replacement therapy during and following tooth extraction or other surgeries (eg polypectomy etc); and
• Short-term treatment not exceeding eight (8) days.

All indications not mentioned within this policy are considered experimental/investigational and therefore non-covered. The scientific evidence has not established the safety and efficacy for use in other indications.

Hemophilia B (i.e., Congenital Factor IX Deficiency, Factor IX Deficiency, Christmas disease)

Factor IX (plasma-derived) [Bebulin, Mononine] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of hemophilia B; and
• At least ONE of the following:
• Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes; or
• Treatment of acute bleeding episode.

Factor IX (plasma-derived) [Profilnine SD and AlphaNine SD] may be considered medically necessary for individuals greater than or equal to seventeen (17) years of age when ALL of the following criteria are met:

• Diagnosis of hemophilia B; and
• At least ONE of the following:
• Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes; or
• Treatment of acute bleeding episode.

Factor IX (recombinant) [BeneFIX, Idelvion, Ixinity, or Rixubis] and Coagulation Factor IX (recombinant), Fc Fusion Protein (Alprolix) may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of hemophilia B; and
• At least ONE of the following:
• Treatment of acute bleeding episode; or
• Routine prophylactic treatment to prevent or reduce the frequency of bleeding episodes; or
• Prevention of bleeding in surgical interventions (i.e., surgical prophylaxis).

Coagulation Factor IX (recombinant), Pegylated (Rebinyn) may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of hemophilia B; and
• At least ONE of the following:
• Treatment of acute bleeding episode; or
• Prevention of bleeding in surgical interventions (i.e., surgical prophylaxis).

Anti-Inhibitor Coagulant Complex (plasma-derived) [FEIBA NF, FEIBA VH] and factor VIIa (recombinant) [NovoSeven RT] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of hemophilia B; and
• Documentation of inhibitors (e.g., Bethesda inhibitor assay); and
• At least ONE of the following:
• Treatment of acute bleeding episode; or
• Prevention of bleeding in surgical interventions (i.e., surgical prophylaxis); or
• Routine prophylactic treatment of severe status less than 1% of normal factor (less than 0.01 IU/ml); or
• Prophylactic therapy of documented history of one (1) or more episodes of spontaneous bleeding into joints.

Tranexamic acid [Cyklokapron] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of hemophilia B; and
• Prevention of hemorrhage and reduction of the need for replacement therapy during and following tooth extraction; and
• Short-term treatment not exceeding eight (8) days.

All indications not mentioned within this policy are considered experimental/investigational and therefore non-covered. The scientific evidence has not established the safety and efficacy for use in other indications.

Immune Tolerance Induction

High-dose immune tolerance induction may be considered medically necessary when ALL of the following criteria are met:

• Member has a diagnosis of hemophilia A or hemophilia B; and
• Member has inhibitors (anti-factor VIII:c or IX:c antibodies); and
• Anti-hemophilic factor or Factor IX survival and recovery of anti-hemophilic factor levels after infusion are abnormal; and
• Attempts to lower antibody levels with either immunosuppressant or corticosteroids have been unsuccessful; and
• Dosing continues beyond 14 days.

Immune tolerance induction limitations:

• Continued immune tolerance induction is considered not medically necessary when ALL of the following criteria are met:
• Anti-hemophilic factor or factor IX survival after infusion is normal (6-hr level at least 46 % of 10-min level); and
• Inhibitor levels become undetectable; and
• Recovery of anti-hemophilic factor or factor IX levels after infusion is normal (defined as at least 85 % of the expected for individuals without inhibitors).  
• Cases in which members are on immune tolerance induction for six (6) months or more may be referred to a hemophilia treatment center for review of medical necessity to determine whether continued immune tolerance therapy is medically necessary; and 
• Alprolix, Idelvion, Ixinity, and Hemlibra are not indicated for induction of immune tolerance.  

All indications not mentioned within this policy are considered experimental/investigational and therefore non-covered. The scientific evidence has not established the safety and efficacy for use in other indications.

von Willebrand Disease (vWD)

vWF complex (recombinant) [Vonvendi] maybe considered medically necessary in adults greater than or equal to 18 years of age when ALL of the following criteria are met:

• Diagnosis of von Willebrand Disease; and
• At least ONE of the following:
• Treatment of acute bleeding episode; or
• Prevention of bleeding in surgical interventions (i.e., surgical prophylaxis).

Factor VIII (plasma-derived)/vWF complex (plasma-derived) [Alphanate] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of mild or moderate von Willebrand disease; and
• History of failure, contraindication or intolerance to treatment with Desmopressin; and
• At least ONE of the following:
  • Treatment of spontaneous and trauma-induced bleeding episodes; or
  • Prevention of excessive bleeding during surgery (i.e., surgical prophylaxis).

Factor VIII (plasma-derived)/vWF complex (plasma-derived) [Humate-P] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of von Willebrand disease; and
• History of failure, contraindication or intolerance to treatment with Desmopressin; and
• At least ONE of the following:
  • Treatment of spontaneous and trauma-induced bleeding episodes; or
  • Prevention of excessive bleeding during surgery (i.e., surgical prophylaxis).

Factor VIII (plasma-derived)/vWF complex (plasma-derived) [Wilate] may be considered medically necessary when ALL of the following criteria are met:

• Diagnosis of von Willebrand disease; and
• ANY of the following:
  • Perioperative management of bleeding; or
  • Treatment of spontaneous and trauma-induced bleeding episodes.

 All indications not mentioned within this policy are considered experimental/investigational and therefore non-covered. The scientific evidence has not established the safety and efficacy for use in other indications.

Experimental/Investigational (E/I) services are not covered regardless of place of service.

Evidence based guidelines support the administration of this drug in alternative sites of care such as the home, office or outpatient ambulatory infusion centers. Administration of infusible drugs at alternate sites of care is based upon the professional judgment of the provider, and taken into account the clinical appropriateness for each individual patient.

The administration of clotting factors and coagulant blood products is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

Services that do not meet the criteria of this policy will be considered experimental/investigational (E/I). A network provider can bill the member for the experimental/investigational service. The provider must give advance written notice informing the member that the service has been deemed E/I. The member must be provided with an estimate of the cost and the member must agree in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.

A network provider cannot bill the member for the non-covered service.

• Link to Provider Resource Center for the Medical Policy Update

08/2017 Expanded Criteria for Hemophilia Treatments.
08/2018 Expanded Guidelines for Hemophilia Treatments.

• Link to Diagnosis Codes

• Link to References