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09-J0000-34

Original Effective Date: 03/15/01

Reviewed: 04/12/17

Revised: 05/15/17

Subject: Clotting Factors and Coagulant Blood Products

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates
           

DESCRIPTION:

Hemostasis is regulated by a series of complex procoagulant and anticoagulant actions that involve the vessel wall, platelets, and the coagulation and fibrinolytic systems. An imbalance in any direction can result in coagulation disorders and specifically in a bleeding disorder when there is a deficiency of coagulation factors. Coagulation factor deficiencies present more frequently as an acquired deficiency such as disseminated intravascular coagulation (DIC) or vitamin K deficiency; inherited deficiencies are rarer, with the most common being deficiencies of factor VIII (hemophilia A) and factor IX (hemophilia B). Treatment of both acquired and inherited deficiencies involve factor replacement using either recombinant or purified plasma-derived products.

Rarely, individuals develop neutralizing antibodies, or inhibitors, to factor VIII and IX resulting in a decreased clinical response to factor replacement. Inhibitors are measured with the Bethesda assay with titers reported in Bethesda units (BU). One BU is the amount of inhibitor needed to inactivate half of factor VIII or IX in a mixture of normal and inhibitor-containing plasma. Patients with inhibitors are classified as either low responders (<5 BU/mL) or high responders (>5 BU/mL). Administering high and more frequent doses of factor products may effectively manage bleeding episodes in low responders, while high responders should be managed with agents that bypass the factor to which the antibody is directed.

A brief overview of covered clotting factors and coagulant blood products is provided in Table 1.

TABLE 1

Review of clotting factor and coagulant blood products

Product

Notes

Anti-inhibitor Coagulant Complex

Feiba

• Bypassing agent derived from human plasma

• Contains factors II, VIIa, IX, and X

• Labeled with units of factor VIII bypassing activity

• Decreases activated partial thromboplastin time (aPTT)

• Manufacturer suggests use as a first-line agent if inhibitor titer is greater than 10 BU/mL and second-line agent if inhibitor titer is 5-10 BU/mL

• Inadequate response to treatment may result from an abnormal platelet count or impaired platelet function

Fibrinogen concentrate

RiaSTAP

• Derived from human plasma

• Factor I is a substrate for thrombin, factor XIIIa, and plasmin

Factor VIIa

NovoSeven, NovoSeven RT

• Bypassing agent generated from cloned human factor VII expressed in baby hamster kidney cells

• Contains only activated factor VIIa

• Short dosing interval (half-life: 3 hours)

Factor VIII

Human: Hemofil M, Monoclate-P

Recombinant: Advate, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Nuwiq, Recombinate, ReFacto, Xyntha

• Products differ based on purity and source of factor VIII

• Facilitates the activation of factor X causing the formation of thrombin and fibrin

• Factor VIII potency differs by product

Factor VIII/VWF complex

Alphanate, Humate P, Koate-DVI, Octanate, Wilate

• Derived from human plasma

• Factor VIII facilitates the activation of factor X causing the formation of thrombin and fibrin

• Von Willebrand factor promotes platelet aggregation and adhesion to damaged vascular endothelium

• Factor VIII potency differs by product

von Willebrand factor, recombinant

Vonvendi

• Purified recombinant von Willebrand factor (rVWF) expressed in Chinese Hamster Ovary (CHO) cells

• Acts to promote hemostasis by mediating platelet adhesion to damaged vascular sub-endothelial matrix (e.g. collagen) and platelet aggregation, and as a carrier protein for factor VIII, protecting it from rapid proteolysis

Antihemophilic factor porcine, recombinant

Obizur

• Derived from baby hamster kidney cell line which secrete recombinant porcine factor VIII in cell culture medium

• Replaces the inhibited factor VIII needed for effective hemostasis and normalizes the aPTT over the effective dosing period.

• Factor VIII activity, not aPTT, should not be used as a measure of efficacy during treatment

Antihemophilic factor (recombinant), single chain

Afstyla

• Uses a covalent bond to form a single polypeptide-chain (one structural entity) to improve the stability of factor VIII and provide longer-lasting factor VIII activity

Antihemophilic factor Fc fusion protein, recombinant (rFVIIIFc)

Eloctate

• Antihemophilic factor (Factor VIII) is covalently linked to the Fc domain of human immunoglobulin G1

• Binding of Fc domain delays degradation to increase circulating half-life of factor VIII

Antihemophilic factor pegylated, recombinant

Adynovate

• Pegylated form of recombinant antihemophilic factor (Factor VIII)

• Exhibits an extended terminal half-life through pegylation of the parent molecule, which reduces binding to the physiological factor VIII

clearance receptor (LRP1)

Factor IX

Human: AlphaNine SD, Mononine

Recombinant: BeneFIX, RIXUBIS, Ixinity

• BeneFIX and RIXUBIS are produced in a Chinese hamster ovary cell line

• Mononine is purified with a murine monoclonal antibody

• Combines with factor VIII to activate factor X (factor X converts prothrombin to thrombin; thrombin converts fibrinogen to fibrin clot)

Factor IX complex

Bebulin, Profilnine SD

• Derived from human plasma

• Contains varying concentrations of factors II, VII, and X (in addition to factor IX)

Factor IX albumin fusion protein, recombinant

Idelvion

• Recombinant factor IX molecule is genetically fused to recombinant albumin

• Fusing to albumin prolongs the half-life of factor IX

Factor IX Fc fusion protein, recombinant

Alprolix

• Human coagulation factor IX is covalently linked to the Fc domain of human immunoglobulin G1

• Binding of Fc domain delays degradation to increase circulating half-life of factor IX

Coagulation Factor X, human

Coagadex

• Derived from human plasma

• Factor X is an inactive zymogen, which can be activated by Factor IXa (via the intrinsic pathway) or by Factor VIIa (via the extrinsic pathway)

Factor XIII

Human: Corifact

Recombinant: Tretten

• Circulates in the blood and is found in platelets, macrophages, and monocytes

• Promotes cross-linking of fibrin during the coagulation process, and protects the newly formed clot from fibrinolysis

POSITION STATEMENT:

Initiation and continuation of a clotting factor or coagulant blood product meets the definition of medical necessity when all of the following criteria are met:

1. Member has seen a board certified hematologist or hematologist-oncologist and that physician has performed a complete hematologic and musculoskeletal assessment in the past 12 months – documentation from medical record must be provided

2. Clotting factor or coagulant blood product is prescribed by a board certified hematologist or hematologist-oncologist

3. Factor replacement protocol (including dosing for both acute and prophylactic management) is provided

4. Factor replacement protocol has been developed or evaluated by a board certified hematologist or hematologist-oncologist within the past 12 months – documentation from the medical record must be provided

5. Member meets product-specific criteria outlined in Table 2.

TABLE 2

Table 2. Criteria for use of clotting factor and coagulant blood products*

Product

Criteria

Anti-inhibitor Coagulant Complex

Feiba

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Member is diagnosed with one of the following:

a. Hemophilia A with inhibitors

b. Hemophilia B with inhibitors

c. Acquired inhibitors to factors VIII, XI, and XII

2. Indication for use is treatment or prophylaxis of bleeding

3. Dose does not exceed 200 units/kg/day

Approval duration: 1 year

Fibrinogen concentrate

RiaSTAP

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Member is diagnosed with a congenital fibrinogen deficiency (e.g., afibrinogenemia, hypofibrinogenemia) that has been confirmed by blood coagulation testing

2. Indication for use is treatment of acute bleeding episodes

3. Use is NOT for treatment of dysfibrinogenemia

4. Dose does not exceed 70 mg/kg/dose unless member’s baseline fibrinogen level is known

Approval duration: 1 year

Factor VIIa

NovoSeven, NovoSeven RT

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Indication for use is one of the following:

a. Treatment of acute bleeding episode

b. Prophylaxis of post-operative bleeding

2. Member is diagnosed with one of the following and dose does not exceed diagnosis specific limitations:

a. Member is diagnosed with hemophilia A with inhibitors AND bolus dose does not exceed 120 mcg/kg/dose in adults or 150 mcg/kg/dose in children

b. Member is diagnosed with hemophilia B with inhibitors AND bolus dose does not exceed 120 mcg/kg/dose in adults or 150 mcg/kg/dose in children

c. Member is diagnosed with acquired hemophilia AND bolus dose does not exceed 90 mcg/kg/dose

d. Member is diagnosed with a congenital factor VII deficiency AND bolus dose does not exceed 30 mcg/kg/dose

e. Member is diagnosed with Glanzmann's thrombasthenia AND bolus dose does not exceed 90 mcg/kg/dose

Approval duration: 1 year

Factor VIII

Human: Hemofil M, Monoclate-P

Recombinant: Advate, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Nuwiq, Recombinate, ReFacto, Xyntha

Initiation and continuation meet the definition of medical necessity if ANY of the following are met:

1. Member is diagnosed with hemophilia A AND all of the following are met:

a. Indication for use is ONE of the following:

i. Treatment of bleeding

ii. Prophylaxis of post-operative bleeding including dental bleeding prophylaxis (e.g., tooth extraction)

iii. Routine prophylaxis of bleeding AND member meets ONE of the following:

1. Endogenous factor VIII is less than or equal to 1 IU/dL (1%)

2. Endogenous factor VIII is less than or equal to 40 IU/dL (40%) AND member has documented history of 2 or more bleeds into large joints (i.e., ankles, knees, hips, elbows, shoulders)

iv. Immune tolerance induction therapy AND all of the following are met:

1. Inhibitor titers are less than 10 Bethesda units/mL – laboratory documentation must be provided

2. Inhibitor titers will be measured every six months

b. Dose does not exceed indication specific limitations:

i. Treatment of bleeding: 50 IU/kg/dose (100 IU/kg/dose if inhibitor titers are less than 10 Bethesda units/mL)

ii. Prophylaxis of post-operative bleeding including dental bleeding prophylaxis (e.g., tooth extraction): 50 IU/kg/dose

iii. Routine prophylaxis: 50 IU/kg/dose three times per week or every other day

iv. Immune tolerance induction therapy: 200 IU/kg/day

2. Member is diagnosed with von Willebrand disease AND all of the following are met:

a. Indication for use is treatment or prophylaxis of bleeding

b. Use of desmopressin is known or suspected to be ineffective or contraindicated

c. Dose does not exceed indication specific limitations: (Alphanate, Humate P ONLY)

i. Treatment of bleeding: 80 IU/kg/dose (Humate P)

ii. Prophylaxis of post-operative bleeding including dental bleeding prophylaxis (e.g., tooth extraction): 60 IU/kg/dose (Alphanate, Humate P); 75 IU/kg/dose if age < 18 years (Alphanate)

Approval duration: 1 year

Factor VIII/VWF complex

Alphanate, Humate P, Koate-DVI, Octanate

Factor VIII/VWF complex

Wilate

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Member is diagnosed with von Willebrand disease

2. Indication for use is treatment of spontaneous or trauma-induced bleeding

3. Use of desmopressin is known or suspected to be ineffective or contraindicated

4. Dose does not exceed 60 IU/kg/dose

Approval duration: 1 year

von Willebrand factor, recombinant

Vonvendi

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Member is diagnosed with von Willebrand disease

2. Indication for use is treatment of spontaneous or trauma-induced bleeding

3. Use of desmopressin is known or suspected to be ineffective or contraindicated

4. Member is 18 years of age and older

5. Dose does not exceed 80 IU/kg/dose

Approval duration: 1 year

Antihemophilic factor porcine, recombinant

Obizur

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Member is diagnosed with acquired hemophilia A

2. Indication for use is treatment of bleeding

3. Dose does not exceed 200 IU/kg/dose

Approval duration: 1 year

Antihemophilic factor (recombinant), single chain

Afstyla

Initiation meets the definition of medical necessity for ANY of the following indications if ALL indication specific criteria are met:

1. Treatment of bleeding

a. Member is diagnosed with hemophilia A

b. Member does not have inhibitors to factor VIII

c. Member has tried and had an inadequate response† to a two month trial of at least one of the following factor VIII products when used as part of a factor replacement protocol for acute management of bleeding:

i. Human (plasma-derived) Factor VIII: Hemofil M, Monoclate-P

ii. Recombinant Factor VIII: Advate, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Nuwiq, Recombinate, ReFacto, Xyntha

d. Dose does not exceed 50 IU/kg/dose

2. Prophylaxis of post-operative bleeding, including dental bleeding prophylaxis (e.g., tooth extraction)

a. Member is diagnosed with hemophilia A

b. Member does not have inhibitors to factor VIII

c. Member has tried and had an inadequate response† to at least one of the following factor VIII products when used as part of a factor replacement protocol for prophylaxis of post-operative bleeding:

i. Human (plasma-derived) Factor VIII: Hemofil M, Monoclate-P

ii. Recombinant Factor VIII: Advate, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Nuwiq, Recombinate, ReFacto, Xyntha

d. Dose does not exceed 50 IU/kg/dose

3. Routine prophylaxis of bleeding

a. Member is diagnosed with hemophilia A

b. Member does not have inhibitors to factor VIII

c. Member meets ONE of the following:

i. Endogenous factor VIII is less than or equal to 1 IU/dL (1%)

ii. Endogenous factor VIII is less than or equal to 40 IU/dL (40%) AND member has documented history of 2 or more bleeds into large joints (i.e., ankles, knees, hips, elbows, shoulders)

d. Member has tried and had an inadequate response† to at least one of the following factor VIII products when used as part of a factor replacement protocol for prophylactic management of bleeding:

i. Human (plasma-derived) Factor VIII: Hemofil M, Monoclate-P

ii. Recombinant Factor VIII: Advate, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Nuwiq, Recombinate, ReFacto, Xyntha

e. Dose does not exceed 50 IU/kg/dose every three times per week

Approval duration: 6 month

Continuation meets the definition of medical necessity if ALL criteria are met:

1. Member meets Florida Blue’s initial criteria or was previously approved by another health plan

2. Member demonstrates a beneficial response according to indication for use:

a. Treatment of bleeding: Bleeding episode controlled with 2 or fewer injections

b. Routine prophylaxis of bleeding: 75% reduction in ABR

3. Dose does not exceed indication-specific limitations:

a. Treatment of bleeding: 50 IU/kg/dose

b. Prophylaxis of post-operative bleeding, including dental bleeding prophylaxis (e.g., tooth extraction): 50 IU/kg/dose

c. Routine prophylaxis of bleeding: 50 IU/kg/dose every three times per week

Approval duration: 1 year

Antihemophilic factor Fc fusion protein, recombinant (rFVIIIFc)

Eloctate

Initiation meets the definition of medical necessity for ANY of the following indications if ALL indication specific criteria are met:

1. Treatment of bleeding

a. Member is diagnosed with hemophilia A

b. Member does not have inhibitors to factor VIII

c. Member has tried and had an inadequate response† to a two month trial of at least one of the following factor VIII products when used as part of a factor replacement protocol for acute management of bleeding:

i. Human (plasma-derived) Factor VIII: Hemofil M, Monoclate-P

ii. Recombinant Factor VIII: Advate, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Nuwiq, Recombinate, ReFacto, Xyntha

d. Dose does not exceed 50 IU/kg/dose

2. Prophylaxis of post-operative bleeding, including dental bleeding prophylaxis (e.g., tooth extraction)

a. Member is diagnosed with hemophilia A

b. Member does not have inhibitors to factor VIII

c. Member has tried and had an inadequate response† to at least one of the following factor VIII products when used as part of a factor replacement protocol for prophylaxis of post-operative bleeding:

i. Human (plasma-derived) Factor VIII: Hemofil M, Monoclate-P

ii. Recombinant Factor VIII: Advate, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Nuwiq, Recombinate, ReFacto, Xyntha

d. Dose does not exceed 60 IU/kg/dose

3. Routine prophylaxis of bleeding

a. Member is diagnosed with hemophilia A

b. Member does not have inhibitors to factor VIII

c. Member meets ONE of the following:

i. Endogenous factor VIII is less than or equal to 1 IU/dL (1%)

ii. Endogenous factor VIII is less than or equal to 40 IU/dL (40%) AND member has documented history of 2 or more bleeds into large joints (i.e., ankles, knees, hips, elbows, shoulders)

d. Member has tried and had an inadequate response† to at least one of the following factor VIII products when used as part of a factor replacement protocol for prophylactic management of bleeding:

i. Human (plasma-derived) Factor VIII: Hemofil M, Monoclate-P

ii. Recombinant Factor VIII: Advate, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Nuwiq, Recombinate, ReFacto, Xyntha

e. Dose does not exceed 65 IU/kg/dose every three to five days

Approval duration: 6 month

Continuation meets the definition of medical necessity if ALL criteria are met:

1. Member meets Florida Blue’s initial criteria or was previously approved by another health plan

2. Member demonstrates a beneficial response according to indication for use:

a. Treatment of bleeding: Bleeding episode controlled with 2 or fewer injections

b. Routine prophylaxis of bleeding: 75% reduction in ABR

3. Dose does not exceed indication-specific limitations:

a. Treatment of bleeding: 50 IU/kg/dose

b. Prophylaxis of post-operative bleeding, including dental bleeding prophylaxis (e.g., tooth extraction): 60 IU/kg/dose

c. Routine prophylaxis of bleeding: 65 IU/kg/dose every three to five days

Approval duration: 1 year

Antihemophilic factor pegylated, recombinant

Adynovate

Initiation meets the definition of medical necessity for ANY of the following indications if ALL indication specific criteria are met:

1. Treatment of bleeding

a. Member is diagnosed with hemophilia A

b. Member does not have inhibitors to factor VIII

c. Member has tried and had an inadequate response† to a two month trial of at least one of the following factor VIII products when used as part of a factor replacement protocol for acute management of bleeding:

i. Human (plasma-derived) Factor VIII: Hemofil M, Monoclate-P

ii. Recombinant Factor VIII: Advate, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Nuwiq, Recombinate, ReFacto, Xyntha

d. Dose does not exceed 50 IU/kg/dose

2. Routine prophylaxis of bleeding

a. Member is diagnosed with hemophilia A

b. Member does not have inhibitors to factor VIII

c. Member meets ONE of the following:

i. Endogenous factor VIII is less than or equal to 1 IU/dL (1%)

ii. Endogenous factor VIII is less than or equal to 40 IU/dL (40%) AND member has documented history of 2 or more bleeds into large joints (i.e., ankles, knees, hips, elbows, shoulders)

d. Member has tried and had an inadequate response† to at least one of the following factor VIII products when used as part of a factor replacement protocol for prophylactic management of bleeding:

i. Human (plasma-derived) Factor VIII: Hemofil M, Monoclate-P

ii. Recombinant Factor VIII: Advate, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Nuwiq, Recombinate, ReFacto, Xyntha

e. Dose does not exceed 50 IU/kg/dose two times per week

Approval duration: 6 month

Continuation meets the definition of medical necessity if ALL criteria are met:

1. Member meets Florida Blue’s initial criteria or was previously approved by another health plan

2. Member demonstrates a beneficial response according to indication for use:

a. Treatment of bleeding: Bleeding episode controlled with 2 or fewer injections

b. Routine prophylaxis of bleeding: 75% reduction in ABR

3. Dose does not exceed indication-specific limitations:

a. Treatment of bleeding: 50 IU/kg/dose

b. Routine prophylaxis of bleeding: 50 IU/kg/dose two times per week

Approval duration: 1 year

Factor IX, human

AlphaNine SD, Mononine

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Member is diagnosed with hemophilia B

2. Indication for use is treatment or prophylaxis of bleeding

3. Dose does not exceed indication specific limitations:

a. Treatment of bleeding: 120 IU/kg/dose

b. Prophylaxis of post-operative bleeding including dental bleeding prophylaxis (e.g., tooth extraction): 100 IU/kg/dose

c. Routine prophylaxis: 100 IU/kg/dose two or three times per week

Approval duration: 1 year

Factor IX, recombinant

BeneFIX, Ixinity, RIXUBIS

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Member is diagnosed with hemophilia B

2. Indication for use is ONE of the following:

a. Treatment of bleeding

b. Prophylaxis of post-operative bleeding including dental bleeding prophylaxis (e.g., tooth extraction)

c. Routine prophylaxis of bleeding AND member meets ONE of the following:

i. Endogenous factor IX is less than or equal to 1 IU/dL (1%)

ii. Endogenous factor IX is less than or equal to 40 IU/dL (40%) AND member has documented history of 2 or more bleeds into large joints (i.e., ankles, knees, hips, elbows, shoulders)

3. Dose does not exceed indication specific limitations:

a. Treatment of bleeding: 140 IU/kg/dose

b. Prophylaxis of post-operative bleeding including dental bleeding prophylaxis (e.g., tooth extraction): 140 IU/kg/dose

c. Routine prophylaxis: 100 IU/kg/dose two or three times per week (BeneFIX, Ixfinity); 80 IU/kg/dose two times per week (RIXUBIS)

Approval duration: 1 year

Factor IX complex

Bebulin, Profilnine SD

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Member is diagnosed with hemophilia B, factor II deficiency, or factor X deficiency

2. Indication for use is ONE of the following:

a. Treatment of bleeding

b. Prophylaxis of post-operative bleeding including dental bleeding prophylaxis (e.g., tooth extraction)

c. Routine prophylaxis of bleeding

3. Dose does not exceed 120 IU/kg/dose (Bebulin), 100 IU/kg/dose (Profilnine SD)

Approval duration: 1 year

Factor IX albumin fusion protein, recombinant

Idelvion

Initiation meets the definition of medical necessity for ANY of the following indications if ALL indication specific criteria are met:

1. Treatment of bleeding

a. Member is diagnosed with hemophilia B

b. Member does not have inhibitors to factor IX

c. Member has tried and had an inadequate response† to a two month trial of at least one of the following factor IX products when used as part of a factor replacement protocol for acute management of bleeding:

i. Human (plasma-derived) Factor IX (human): AlphaNine SD, Mononine

ii. Factor IX, recombinant: BeneFIX, Ixinity, RIXUBIS

d. Dose does not exceed 100 IU/kg/dose

2. Prophylaxis of post-operative bleeding, including dental bleeding prophylaxis (e.g., tooth extraction)

a. Member is diagnosed with hemophilia B

b. Member does not have inhibitors to factor IX

c. Member has tried and had an inadequate response† to a two month trial of at least one of the following factor IX products when used as part of a factor replacement protocol for prophylaxis of post-operative bleeding:

i. Human (plasma-derived) Factor IX (human): AlphaNine SD, Mononine

ii. Factor IX, recombinant: BeneFIX, Ixinity, RIXUBIS

d. Dose does not exceed 100 IU/kg/dose

3. Routine prophylaxis of bleeding

a. Member is diagnosed with hemophilia B

b. Member does not have inhibitors to factor IX

c. Member meets ONE of the following:

i. Endogenous factor IX is less than or equal to 1 IU/dL (1%)

ii. Endogenous factor IX is less than or equal to 40 IU/dL (40%) AND member has documented history of 2 or more bleeds into large joints (i.e., ankles, knees, hips, elbows, shoulders)

d. Member has tried and had an inadequate response† to a two month trial of at least one of the following factor IX products when used as part of a factor replacement protocol for prophylactic management of bleeding t:

i. Human (plasma-derived) Factor IX (human): AlphaNine SD, Mononine

ii. Factor IX, recombinant: BeneFIX, Ixinity, RIXUBIS

e. Dose does not exceed:

i. Age 12 years and older: 40 IU/kg one time per week or 75 IU/kg every 14 days

ii. Age less than 12 years: 55 IU/kg every 7 days

Approval duration: 6 month

Continuation meets the definition of medical necessity if ALL criteria are met:

1. Member meets Florida Blue’s initial criteria or was previously approved by another health plan

2. Member demonstrates a beneficial response according to indication for use:

a. Treatment of bleeding: Bleeding episode controlled with 2 or fewer injections

b. Routine prophylaxis of bleeding: 75% reduction in ABR

3. Dose does not exceed indication-specific limitations:

a. Treatment of bleeding: 100 IU/kg/dose

b. Prophylaxis of post-operative bleeding, including dental bleeding prophylaxis (e.g., tooth extraction): 100 IU/kg/dose

c. Routine prophylaxis of bleeding:

i. Age 12 years and older: 40 IU/kg one time per week or 75 IU/kg every 14 days

ii. Age less than 12 years: 55 IU/kg every 7 days

Approval duration: 1 year

Factor IX Fc fusion protein, recombinant

Alprolix

Initiation meets the definition of medical necessity for ANY of the following indications if ALL indication specific criteria are met:

1. Treatment of bleeding

a. Member is diagnosed with hemophilia B

b. Member does not have inhibitors to factor IX

c. Member has tried and had an inadequate response† to a two month trial of at least one of the following factor IX products when used as part of a factor replacement protocol for acute management of bleeding:

i. Human (plasma-derived) Factor IX (human): AlphaNine SD, Mononine

ii. Factor IX, recombinant: BeneFIX, Ixinity, RIXUBIS

d. Dose does not exceed 100 IU/kg/dose

2. Prophylaxis of post-operative bleeding, including dental bleeding prophylaxis (e.g., tooth extraction)

a. Member is diagnosed with hemophilia B

b. Member does not have inhibitors to factor IX

c. Member has tried and had an inadequate response† to a two month trial of at least one of the following factor IX products when used as part of a factor replacement protocol for prophylaxis of post-operative bleeding:

i. Human (plasma-derived) Factor IX (human): AlphaNine SD, Mononine

ii. Factor IX, recombinant: BeneFIX, Ixinity, RIXUBIS

d. Dose does not exceed 100 IU/kg/dose

3. Routine prophylaxis of bleeding

a. Member is diagnosed with hemophilia B

b. Member does not have inhibitors to factor IX

c. Member meets ONE of the following:

i. Endogenous factor IX is less than or equal to 1 IU/dL (1%)

ii. Endogenous factor IX is less than or equal to 40 IU/dL (40%) AND member has documented history of 2 or more bleeds into large joints (i.e., ankles, knees, hips, elbows, shoulders)

d. Member has tried and had an inadequate response† to a two month trial of at least one of the following factor IX products when used as part of a factor replacement protocol for prophylactic management of bleeding t:

i. Human (plasma-derived) Factor IX (human): AlphaNine SD, Mononine

ii. Factor IX, recombinant: BeneFIX, Ixinity, RIXUBIS

e. Dose does not exceed 50 IU/kg/dose one time per week or 100 IU/kg/dose every 10 days

Approval duration: 6 month

Continuation meets the definition of medical necessity if ALL criteria are met:

1. Member meets Florida Blue’s initial criteria or was previously approved by another health plan

2. Member demonstrates a beneficial response according to indication for use:

a. Treatment of bleeding: Bleeding episode controlled with 2 or fewer injections

b. Routine prophylaxis of bleeding: 75% reduction in ABR

3. Dose does not exceed indication-specific limitations:

a. Treatment of bleeding: 100 IU/kg/dose

b. Prophylaxis of post-operative bleeding, including dental bleeding prophylaxis (e.g., tooth extraction): 100 IU/kg/dose

c. Routine prophylaxis of bleeding: 50 IU/kg/dose one time per week or 100 IU/kg/dose every 10 days

Approval duration: 1 year

Coagulation Factor X, human

Coagadex

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Member is diagnosed with hereditary factor X deficiency

2. Indication for use is one of the following:

a. Treatment of bleeding

b. Perioperative management of bleeding AND member has mild hereditary factor X deficiency

3. Dose does not exceed indication specific limitations:

a. Treatment of bleeding: 25 IU/kg/dose one time every 24 hours

b. Perioperative management of bleeding: 50 IU/kg/dose

Approval duration: 1 year

Factor XIII, human

Corifact

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Member is diagnosed with congenital factor XIII deficiency

2. Indication for use is prophylaxis of bleeding

3. Dose does not exceed 45 IU/kg/dose every 28 days

Approval duration: 1 year

Factor XIII, recombinant

Tretten

Initiation and continuation meet the definition of medical necessity if ALL criteria are met:

1. Member is diagnosed with congenital factor XIII deficiency

2. Indication for use is prophylaxis of bleeding

3. Dose does not exceed 35 IU/kg/dose every 28 days

Approval duration: 1 year

*Due to variations in potency and limited vial sizes, doses may be equal to or less than 110% of the doses listed above.

Inadequate response is defined as clinically evident bleeding at indication-specific doses. For prophylactic management of bleeding, clinically evident bleeding includes any of the following: 1 or more episodes of spontaneous bleeding into joint; 1 or more episodes of spontaneous bleeding into the central nervous system; or 4 or more episodes of soft tissue bleeding in an 8 week period.

Anti-inhibitor Coagulant Complex, Factor VIIa, Factor VIII, Factor VIII/VWF complex, Antihemophilic factor pegylated, Antihemophilic factor Fc fusion protein, Factor IX, Factor IX Fc fusion protein, Factor IX albumin fusion protein, Factor IX complex, Coagulation Factor X, and Factor XIII are considered experimental or investigational for all other indications as there is insufficient clinical evidence to support use.

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USE.

Dosage and administration varies considerably with each product and is based on patient weight. A brief overview of selected products is provided in Table 3; however, it is strongly recommended that the prescriber refer to product-specific labeling for complete dosing and administration instructions.

Table 3

Dosage and administration of select clotting factor and coagulant blood products

Product

Dosing/Administration

Anti-inhibitor Coagulant Complex

Feiba

General dosing recommendation:

50 to 100 units/kg IV (maximum total daily dose: 200 units/kg)

Joint hemorrhage:

50 to 100 units/kg IV every 12 hours; continue until clinical improvement achieved (e.g., pain relief, reduced swelling, joint mobilization)

Mucous membrane bleeding:

50 to 100 units/kg IV every 6 hours; carefully monitor patient and perform repeated measurements hemoglobin/hematocrit

Soft tissue hemorrhage (e.g., retroperitoneal bleeding):

100 units/kg IV every 12 hours

Other severe hemorrhage (e.g., CNS bleed):

100 units/kg every 6 to 12 hours; do not exceed maximum daily dose of 200 units/kg unless bleeding severity warrants use

Fibrinogen concentrate

RiaSTAP

Baseline fibrinogen concentration NOT known:

70 mg/kg IV (rate not to exceed 5 mL/min)

Baseline fibrinogen concentration known:

Calculate dose using known and target plasma fibrinogen level as:

Dose (mg/kg) =

[Target plasma fibrinogen (mg/dL) – Measured plasma fibrinogen (mg/dL)] / 1.7 mg/dL

Pediatric (age less than 16 years) :

A shorter half-life and faster clearance were observed in pediatric subjects (n=4)

Factor VIIa

NovoSeven, NovoSeven RT

Administer by slow IV injection over 2 to 5 minutes within 3 hours of reconstitution

Acute bleeding episodes in hemophilia A or B with inhibitors:

90 mcg/kg every 2 hours until hemostasis achieved, then every 3 to 6 hours to maintain hemostatic plug

Bleeding prophylaxis during surgical interventions in hemophilia A or B with inhibitors:

90 mcg/kg immediately before the intervention, then every 2 hours for the duration of the surgery

• Minor surgery: Continue dosing every 2 hours for the first 48 hours after surgery, then every 2 to 6 hours until healing has occurred

• Major surgery: Continue dosing every 2 hours for the first 5 days after surgery, then every four hours until healing has occurred

Congenital factor VII deficiency:

15-30 mcg/kg every 4 to 6 hours until hemostasis is achieved

Acquired hemophilia:

70 to 90 mcg/kg every 2 to 3 hours until hemostasis is achieved

Factor XIII

Human: Corifact

Initial dose:

40 IU/kg IV (rate not to exceed 4 mL/min) every 28 days to maintain 5 to 20% trough level of factor XIII activity

Dosing adjustments:

Adjust dose ± 5 IU/kg given the most recent trough factor XIII activity.

Recommended dose adjustments based on the Berichrom activity assay are given as an example below:

• One trough level less than 5%: Increase dose by 5 IU/kg

• Trough level 5 to 20%: No change

• Two trough levels of greater than 20%: Decrease dose by 5 IU/kg

• One trough level greater than 25%: Decrease dose by 5 IU/kg

Perioperative management of surgical bleeding

Individualize the dose based on the factor XIII activity level, type of surgery, and clinical response.

• Time since last dose is less than 7 days: Additional dose may not be needed

• Time since last dose is 7 to 21 days: Partial or full dose may be needed

• Time since last dose is greater than 21 days: Full dose may be given

PRECAUTIONS:

The possibility of contamination with hepatitis and other viral or bacterial infections exists for all products derived from or purified with human blood components. The manufacturing processes are designed to reduce the risk of transmitting viral infection; however, none of the processes are completely effective. There is also the possibility that unknown infectious agents may be present. It is recommended that all members with hemophilia receive vaccination against hepatitis A and B at birth or at diagnosis of hemophilia.

Specific precautions and warnings are highlighted in Table 4.

Table 4

Precautions and warnings of clotting factor and coagulant blood products

Product

Precautions/Warnings

Anti-inhibitor Coagulant Complex

Feiba

Use is contraindicated in individuals with acute thrombosis, embolism, or significant signs of disseminated intravascular coagulation (DIC) (Boxed Warning)

Fibrinogen concentrate

RiaSTAP

Allergic-anaphylactic reactions and thromboembolic episodes have been reported

Factor VIIa

NovoSeven, NovoSeven RT

Arterial and venous thrombotic and thromboembolic events are associated with use (Boxed Warning)

Factor VIII

Human: Hemofil M, Monoclate-P

Recombinant: Advate, Helixate FS, Kogenate FS, Kovaltry, Novoeight, Nuwiq, Recombinate, ReFacto, Xyntha

Use with all factor VIII products has been associated with development of inhibitors.

Monoclonal antibody-purified and recombinant antihemophilic factor products contain varying amounts of animal protein and should be used with caution in patients with bovine protein hypersensitivity, hamster protein hypersensitivity, and murine protein hypersensitivity.

Factor VIII/VWF complex

Alphanate, Humate P, Koate-DVI, Octanate, Wilate

Contraindicated in individuals with known anaphylactic or severe systemic reaction to human plasma-derived products. Use has been associated with development of factor VIII or VWF inhibitors.

von Willebrand factor, recombinant

Vonvendi

Use has been associated with development of factor VIII or VWF inhibitors.

Antihemophilic factor porcine, recombinant

Obizur

Contraindicated in individuals with known anaphylactic or severe systemic reaction to hamster protein.

Antihemophilic factor (recombinant), single chain

Afstyla

Hypersensitivity reactions, including anaphylaxis, are possible. Development of Factor VIII neutralizing antibodies (inhibitors) can occur. If expected plasma Factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, perform an assay that measures Factor VIII inhibitor concentration. If the one-stage clotting assay is used, multiply the result by a conversion factor of 2 to determine the patient's Factor VIII activity level

Antihemophilic Fc fusion protein, recombinant (rFVIIIFc)

Eloctate

Allergic-anaphylactic reactions have been reported

Antihemophilic factor pegylated, recombinant

Adynovate

Allergic-anaphylactic reactions have been reported

Factor IX

Human: AlphaNine SD, Mononine

Recombinant: BeneFIX, RIXUBIS, Ixinity

BeneFIX and RIXUBIS are contraindicated in individuals with a known history of hamster protein hypersensitivity. Mononine should not be used in those with murine protein hypersensitivity. Use of all factor IX products have been associated with development of factor IX inhibitors.

Factor IX albumin fusion protein, recombinant

Idelvion

Contraindicated in individuals with known anaphylactic or severe systemic reaction to hamster protein.

Factor IX Fc fusion protein, recombinant

Alprolix

Allergic-anaphylactic reactions and thromboembolic episodes have been reported

Factor IX complex

Bebulin, Profilnine SD

Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections

Coagulation Factor X, human

Coagadex

Hypersensitivity reactions, including anaphylaxis, are possible. Development of neutralizing antibodies (inhibitors) may occur.

Factor XIII

Human: Corifact

Contraindicated in individuals with known anaphylactic or severe systemic reaction to human plasma-derived products. Use has been associated with development of factor XIII inhibitors.

BILLING/CODING INFORMATION:

The following codes may be used to report clotting factor and coagulant blood products:

HCPCS Coding:

C9140

Injection, factor VIII (antihemophilic factor, recombinant) (Afstyla), 1 IU (Hospital outpatient use ONLY)

J3590

Unclassified biologics

J7175

Injection, factor x, (human), 1 IU [for Coagadex only]

J7178

Injection, human fibrinogen concentrate, 1 mg

J7179

Injection, von willebrand factor (recombinant), (vonvendi), 1 IU vwf:rco

J7180

Injection, factor XIII (antihemophilic factor, human), 1 I.U.

J7181

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

J7182

Injection, factor viii, (antihemophilic factor, recombinant), (novoeight), per iu

J7183

Injection, von Willebrand factor complex (human), Wilate®, 1 I.U. VWF:RCO

J7185

Injection, factor VII (antihemophilic factor, recombinant) (Xyntha), per I.U.

J7186

Injection, antihemophilic factor VIII/Von Willebrand factor complex (human), per factor VIII I.U.

J7187

Injection, von Willebrand Factor complex (Humate-P), per IU vWF-RCO

J7188

Injection, factor viii (antihemophilic factor, recombinant), (obizur), per i.u.

J7189

Factor VIIa (antihemophilic factor, recombinant), per 1 mcg

J7190

Factor VIII (antihemophilic factor, human), per IU

J7192

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

J7193

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

J7194

Factor IX complex, per IU

J7195

Factor IX (antihemophilic factor, recombinant), per IU

J7198

Anti-inhibitor, per IU

J7199

Hemophilia clotting factor, not otherwise classified

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

J7205

Injection, factor viii fc fusion protein (recombinant), per iu

J7207

Injection, factor viii, (antihemophilic factor, recombinant), pegylated, 1 IU

J7209

Injection, factor viii, (antihemophilic factor, recombinant), (Nuwiq), 1 IU

ICD-10 Diagnoses Codes That Support Medical Necessity: (Effective 10/01/15)

D66

Hereditary factor VIII deficiency

D67

Hereditary factor IX deficiency

D68.0

Von Willebrand's disease

D68.1

Hereditary factor XI deficiency

D68.2

Hereditary deficiency of other clotting factors

D68.31

Hemorrhagic disorder due to intrinsic circulating anticoagulants

D68.32

Hemorrhagic disorder due to extrinsic circulating anticoagulants

D68.4

Acquired coagulation factor deficiency

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage Products: The following National Coverage Determination (NCD) was reviewed on the last guideline revised date: Anti-Inhibitor Coagulant Complex (AICC) (110.3) located at cms.gov. The following Local Coverage Determination (LCD) located at www.fcso.com was reviewed on the last guideline revised date: Hemophilia Clotting Factors (L33684).

DEFINITIONS:

Afibrinogenemia: lack of fibrinogen (coagulation factor I) in the blood.

AHF: Nonspecific antihemophilic factor is a preparation of factor VIII administered intravenously for the prevention or treatment of hemorrhage in patients with hemophilia A and the treatment of von Willebrand disease, hypofibrinogenemia and factor VIII deficiency.

AICC: Anti-Inhibitor Coagulant Complex is a concentrated fraction from pooled human plasma, which includes various coagulation factors. It is administered intravenously as an antihemorrhagic in hemophilic patients with inhibitors to factor XIII.

Congenital Afibrinogenemia: a rare autosomal recessive hemorrhagic coagulation disorder, characterized by complete incoagulability of the blood; hemorrhagic manifestations vary from mild to serious.

Dysfibrinogenemia: the presence in the blood of abnormal fibrinogen; both autosomal dominant and recessive forms are known.

Hemophilia B (Christmas Disease): a common type of hemophilia, an X-linked condition caused by deficiency of factor IX.

Hypofibrinogenemia: abnormally low levels of fibrinogen in the blood; called also fibrinogenopenia.

RELATED GUIDELINES:

None applicable.

OTHER:

Guidelines to first and second choice treatment:

Patient's Inhibitor

Clinical Situation

Titer

Minor bleeding

Major bleeding

Surgery (emergency)

Less than 5 BU

AHF

AHF

AHF

5 to 10 BU

AHF

AHF

AHF

AICC

AICC

AICC

More than 10 BU

AICC

AICC

AICC

REFERENCES:

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COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 08/10/16.

GUIDELINE UPDATE INFORMATION:

03/15/01

New Medical Coverage Guideline.

04/15/03

Reviewed with no changes.

01/01/06

Annual HCPCS coding update: added new code J7190 and revised codes J7191 – J7193.

06/15/06

Reviewed with changing of HCPCS codes that were listed as CPT-4 codes and deleted one HCPCS code that was for Factor IX. Also added brand names.

03/15/07

MCG changed to No Longer Reviewed (NLR).

07/15/07

Reviewed guideline: maintain current coverage and limitations. Reformatted guideline, updated internet links and references.

01/01/08

Annual HCPCS coding update: added HCPCS code J7187.

09/15/08

Review and revision to guideline; consisting of renaming guideline, added factor VIIa and factor IX, updated “Description” section, updated position statement, updated coding and updated references and links.

01/01/09

Annual HCPCS coding update: deleted 90765 and 90766; added J7186, 96365 and 96366.

07/01/09

HCPCS 3rd quarter coding update: added Q2023.

10/15/09

Review and revision to guideline; consisting of Incorporating Anti-Inhibitor Coagulant Complex into MCG, adding fibrinogen and updating references.

01/01/10

Annual HCPCS coding update: added J1680 and J7185, revised J7192 descriptor, and deleted Q2023.

05/15/10

Review and revision to guideline; consisting of updating drug lists, ICD-9 coding and HCPCS codes.

01/01/11

Revision to guideline; consisting of updating coding.

05/15/11

Review and revision to guideline; consisting of adding new agent, updating dosing and references.

07/01/11

Revision to guideline; consisting of updating coding.

10/01/11

Revision to guideline; consisting of updating coding.

01/01/12

Revision to guideline; consisting updating coding.

05/15/12

Review and revision to guideline; consisting of updating of descriptions, reformatting updating coding and references

01/01/13

Annual HCPCS Update; added HCPCS code J7178 and removed J1680.

05/15/13

Review and revision to guideline; consisting of updating references, reformatting position statement.

12/15/13

Revision to guideline; consisting of description, position statement, precautions/warnings, and references.

05/15/14

Review and revision to guideline; consisting of position statement, dosage/administration, references, program exceptions.

09/15/14

Revision to guideline; consisting of description, position statement, dosage/administration, precautions, coding, references

01/01/15

Revision to guideline; consisting of coding, position statement, and annual HCPCS coding update.

03/15/15

Revision to guideline; consisting of position statement, coding.

05/15/15

Revision to guideline; consisting of position statement, precautions, references.

09/15/15

Revision to guideline; consisting of position statement, precautions, references.

10/01/15

Revision consisting of update to Program Exceptions section.

01/01/16

Annual HCPCS coding update: added codes J7188 and J7205 and delete code Q9975.

2/15/16

Revision to guideline; consisting of updating position statement.

3/15/16

Revision to guideline; consisting of updating position statement with new FDA approved agents, change MCG name from Antihemophilic Agents to Clotting Factor and Coagulant Blood Products.

04/01/16

Revision to guideline consisting of adding codes C9137 and C9138.

05/15/16

Review and revision to guideline consisting of updating position statement with newly approved agents, updating coding, references.

06/15/16

Revision to guidline consisting of updating coding.

07/15/16

Revision to guideline consisting of updating position statement.

09/15/16

Revision to guideline consisting of updating position statement to include Afstyla.

10/01/16

Revision: New HCPCS code C9139 added.

01/01/17

Revision: added HCPCS codes J7175, J7179, J7202, J7207, and J7209.

05/15/17

Review and revision to guidelines; consisting of updating references.

Date Printed: August 18, 2017: 08:00 PM