ARCHIVED

Medical Policy

Policy Num:       01.001.023
Policy Name:    Hemophilia Antihemophilic Factor
Policy ID:          [01.001.023] [ Ac / L / M+ / P+ ] [0.00.00]

Last Review: July 24, 2024
Next Review: ARCHIVED

Related Policies:

None

Hemophilia Antihemophilic Factor

Population Reference No.

Populations

Interventions

Comparators

Outcomes

Individuals:

With treatment of classic type A hemophilia, including perioperative management.

Interventions of interest:

Antihemophilic factor derived from human plasma.
Monoclate-P
Koate-DVI

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Control and prevention of hemorrhagic episodes in classic hemophilia A.

Interventions of interest:

Antihemophilic factor derived from human plasma
Hemofil M

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Control and prevention of bleeding in adults and children with hemophilia A
Perioperative management of hemophilia A
Prophylaxis to reduce bleeding episodes and reduce joint damage in patients with hemophilia A and no previous damage.

Interventions of interest:

Antihemophilic factor
Recombinant
Helixate FS
Kogenate FS

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Control and prevention of bleeding in adults and children with hemophilia A
Perioperative management of hemophilia A
Can be used to control bleeding in the presence of low levels of factor VIII inhibitors (<10 BU / mL) in hemophilia A

Interventions of interest:

Antihemophilic factor
Recombinant
Recombinate

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Control and prevention of bleeding in adults and children with hemophilia A
Perioperative management of hemophilia A
Routine prophylaxis to prevent / reduce episodes of bleeding in hemophilia A

Interventions of interest:

Antihemophilic factor
Recombinant
Advate

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Control and prevention of hemorrhagic episodes and for surgical prophylaxis in patients with hemophilia A (congenital factor VIII deficiency or classic hemophilia).

Interventions of interest:

Antihemophilic factor
Recombinant
Refacto

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Control and prevention of bleeding in adults and children with hemophilia A
Surgical prophylaxis for hemophilia A

Interventions of interest:

Anti-hemophilic factor
Recombinant (Removal of Domain B)
Xyntha

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Control and prevention of bleeding in patients with hemophilia B, including peri-operative management

Interventions of interest:

Factor IX, recombinant
BeneFIX
Rebinyn

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Control and prevention of bleeding episodes in adults with hemophilia B.
Perioperative management in adults with hemophilia B.
Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults with hemophilia B.

Interventions of interest:

Factor IX, recombinant
Rixubis

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Prevention and control of bleeding in patients with hemophilia B

Interventions of interest:

Factor IX, derived from human plasma
Mononine
AlphaNine SD

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Prevention and control of bleeding episodes in patients with hemophilia B

Interventions of interest:

Factor IX complex derived from human plasma.
Bebulin
Bebulin VH
Profilnine SD

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Control of spontaneous bleeding or for perioperative management of patients with hemophilia A or B and inhibitors

Interventions of interest:

Anti-coagulant inhibitor complex, plasma derivatives
FEIBA NF
FEIBA VH

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Treatment of hemorrhagic episodes and perioperative management in patients with hemophilia A or B and inhibitors or with acquired hemophilia
Treatment of bleeding episodes and peri-operative management in patients with congenital factor VII

Interventions of interest:

Factor VIIa, recombinant
NovoSeven RT

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Treatment and prevention of bleeding in patients with hemophilia A
Treatment of bleeding in adults and children with von Willebrand disease, including spontaneous episodes or trauma-induced episodes
Prevention of excessive bleeding during and after surgery where desmopressin is not effective or contraindicated
Alphanate is not indicated for severe von Willebrand disease.

Interventions of interest:

Complex antihemophilic factor derived from human plasma / von Willebrand factor
Humate-P
Alphanate

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Individuals:

With Treatment of spontaneous hemorrhagic episodes or trauma induced in patients with severe or mild / moderate von Willebrand disease, where desmopressin is not effective or contraindicated.

Interventions of interest:

Factor VII complex derived from human plasma with von Willebrand factor
Wilate

Comparators of interest are:

Standard treatment without management of antihemophilic factors

Relevant outcome includes:

Overall survival
Change in disease status
Quality of life
Treatment related morbidity

Summary

The hemophilias are a group of related bleeding disorders that most commonly are inherited. Inherited bleeding disorders include abnormalities of coagulation factors and platelet function; the most common of these disorders is von Willebrand disease. However, when the term "hemophilia" is used, it most often refers to the following two disorders:

●Factor VIII deficiency (hemophilia A)

●Factor IX deficiency (hemophilia B, also called Christmas disease)

Patients with hemophilia, particularly those with severe disease, develop bleeding episodes that are treated with replacement of the missing factor (ie, factor VIII or factor IX concentrates). A complication of hemophilia treatment is the development of an inhibitor, which usually occurs shortly after replacement therapy has been initiated. The inhibitors are antibodies (primarily IgG) directed against the specific deficient factor.

Development of inhibitors is typically assessed in relationship to the number of exposure days (ie, days on which the patient has received one or more doses of replacement factor).

Objective

This topic reviews the pathophysiology risk factors for inhibitor development in hemophilia A and B, as well as our approach to inhibitor eradication by immune tolerance induction.

Policy Statements

Criteria for the Management of Anti-Hemophilic Factors

1. The prescription must be written by a hematologist.

2. Anti-hemophiliac factors will be covered for indications approved by the FDA (refer to Table 1).

Table 1. Indications

Generic name

Brand name

Indications approved by FDA

Antihemophilic factor derived from human plasma.

Monoclate-P

Koate-DVI

Treatment of classic type A hemophilia, including perioperative management.

Hemofil M

Control and prevention of hemorrhagic episodes in classic hemophilia A.

Antihemophilic factor

Recombinant

Helixate FS

Kogenate FS

Control and prevention of bleeding in adults and children with hemophilia A

Perioperative management of hemophilia A

Prophylaxis to reduce bleeding episodes and reduce joint damage in patients with hemophilia A and no previous damage.

Recombinate

▪ Control and prevention of bleeding in adults and children with hemophilia A

▪ Perioperative management of hemophilia A

▪ Can be used to control bleeding in the presence of low levels of factor VIII inhibitors (<10 BU / mL) in hemophilia A

Advate

▪ Control and prevention of bleeding in adults and children with hemophilia A

▪ Perioperative management of hemophilia A

▪ Routine prophylaxis to prevent / reduce episodes of bleeding in hemophilia A

Refacto

▪ Control and prevention of hemorrhagic episodes and for surgical prophylaxis in patients with hemophilia A (congenital factor VIII deficiency or classic hemophilia).

Anti-hemophilic factor

Recombinant (Removal of Domain B

Xyntha

▪ Control and prevention of bleeding in adults and children with hemophilia A

▪ Surgical prophylaxis for hemophilia A

Factor IX, recombinant

BeneFIX

Rebinyn

▪ Control and prevention of bleeding in patients with hemophilia B, including peri-operative management

Factor IX, recombinant

Rixubis

▪ Control and prevention of bleeding episodes in adults with hemophilia B.

▪ Perioperative management in adults with hemophilia B.

▪ Routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults with hemophilia B.

Factor IX, derived from human plasma

Mononine

AlphaNine SD

▪ Prevention and control of bleeding in patients with hemophilia B

Factor IX complex derived from human plasma.

Bebulin

Bebulin VH

Profilnine SD

▪ Prevention and control of bleeding episodes in patients with hemophilia B

Anti-coagulant inhibitor complex, plasma derivatives

FEIBA NF

FEIBA VH

▪ Control of spontaneous bleeding or for perioperative management of patients with hemophilia A or B and inhibitors

Factor VIIa, recombinant

NovoSeven RT

▪ Treatment of hemorrhagic episodes and perioperative management in patients with hemophilia A or B and inhibitors or with acquired hemophilia

▪ Treatment of bleeding episodes and peri-operative management in patients with congenital factor VII

Complex antihemophilic factor derived from human plasma / von Willebrand factor

Humate-P

Alphanate

▪ Treatment and prevention of bleeding in patients with hemophilia A

▪ Treatment of bleeding in adults and children with von Willebrand disease, including spontaneous episodes or trauma-induced episodes

▪ Prevention of excessive bleeding during and after surgery where desmopressin is not effective or contraindicated

▪ Alphanate is not indicated for severe von Willebrand disease.

Factor VII complex derived from human plasma with von Willebrand factor

Wilate

▪ Treatment of spontaneous hemorrhagic episodes or trauma induced in patients with severe or mild / moderate von Willebrand disease, where desmopressin is not effective or contraindicated.

Geneic

Dose Calculation

Anti-hemophilic factor

derived from human and recombinant plasma

Monoclate-P

Koate-DVI

Hemofil M

Helixate FS

Kogenate FS

Recombinate

Advate

Refacto

Xyntha

The dose of the factor VIII concentrate is mainly based on the severity and location of the bleeding and the necessary levels of the circulation factor.

In the absence of inhibitors, each factor VIII unit will increase endogenous factor levels by 2 IU / dL. The initial dose of the factor can be determined by:

Desired dose (UI) = body weight (kg) x levels of factor x 0.5 intravenously.

The administration rate should not exceed 3 ml / minute for adults and 100 IU / minute in young children.

Circulating levels of factor VIII should be measured 15 minutes after the infusion. Subsequent doses are based on the recovery and half-life of factor VIII for each individual patient.

Factor IX, derived from human plasma

The recovery of factor IX is lower with recombinant factor IX compared to plasma-derived products, which require a higher dose. The initial dose can be calculated as:

Adults

Desired dose (IU) = Body weight (kg) x Factor level intravenously.

0.7

The administration rate should not exceed 3 ml / minute for adults and 100 IU / minute in young children.

Factor IX, recombinant

Rixubis

One international unit of RIXUBIS per kg of bodyweight increased the circulating activity of factor IX by 0.9 international units / dL.

Initial Dose:

Required international units = body weight (kg) x desired factor IX increase (% of normal or IU / dL) x reciprocal of observed recovery (IU / kg per IU / dL).

Maintenance dose depends:

▪ Type of bleed or surgery, the intensity of the hemostatic challenge, and number of days until adequate wound healing is achieved.

Routine prophylaxis:

40 to 60 international units per kg twice weekly.

Plasma-derived Factor IX complex

Bebulin VH

Profilnine SD

Bebulin:

In the absence of inhibitors, each factor IX unit will increase endogenous factor levels of 0.8 IU / dl. The initial dose of concentrate of the factor necessary to achieve the desired level can be determined by:

Desired dose (UI) = Body weight (kg) x Levels of factor x 1.2 intravenously.

Profilnine SD:

In the absence of inhibitors, each factor IX unit will increase endogenous factor levels by 1 IU / dL. The initial dose of factor concentrates needed to achieve the desired level can be determined by:

Desired dose (UI) = Body weight (kg) x Factor level intravenously.

The administration rate should not exceed 2 ml / minute.

Circulating levels of factor IX should be measured 15 minutes after infusion. Subsequent doses are based on the recovery and half-life of factor IX for each individual patient.

Anti-coagulant inhibitor complex, plasma derivatives

FEIBA NF

FEIBA VH

50 to 100 IU / kg administered intravenously every 6 to 12 hours, depending on the severity and location of the hemorrhage.

The administration rate should not exceed 2 IU / kg / minute.

Factor VIIa, recombinant

NovoSeven RT

Hemophilia A or B with inhibitors:

90 mcg / kg every 2 hours as an intravenous bolus until hemostasis is achieved. Doses of 35 to 120 mcg / kg have been used in clinical trials.

Congenital Factor VII Deficiency:

15 to 30 mcg / kg every 4 to 6 hours. Doses as low as 10 mcg / kg have been effective.

Acquired hemophilia:

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

Complex antihemophilic factor derived from human plasma / von Willebrand factor

Humate-P

Alphanate

Hemophilia A:

The dose of factor VIII concentrate is mainly based on the severity and location of the bleeding and the necessary levels of circulation factor.

In the absence of inhibitors, each factor VIII unit will increase the endogenous factor levels of 2 IU / dL. The initial dose of concentrate of the factor necessary to achieve the desired level can be determined by:

Desired dose (UI) = Body weight (kg) x levels of factor x 0.5 intravenously.

The administration rate should not exceed 3 ml / minute for adults and 100 IU / minute in young children.

Circulating levels of factor VIII should be measured 15 minutes after the infusion. Subsequent doses are based on the recovery and half-life of factor VIII for each individual patient.

Von Willebrand disease:

Each unit of endogenous factor VIII will increase the von Willebrand factor by 5 IU / dl

Treatment of bleeding episodes:

40 to 80 IU / kg every 8 to 12 hours intravenously. Subsequent doses are adjusted based on the severity and location of the hemorrhage.

Perioperative management:

One loading dose (eg, 50 to 60 IU / kg) followed by maintenance dose of approximately half the intravenous loading dose. Both the loading dose and the maintenance dose should be adjusted based on the type of surgery.

The administration rate should not exceed 4 ml / minute of Humate-P and 10 ml / minute for Alphanate

Factor VII complex derived from human plasma with von Willebrand factor

Wilate

A loading dose of 20 to 60 IU / kg, depending on the severity of the bleeding, followed by a maintenance dose of 20 to 40 IU / kg every 12 to 24 hours intravenously.

3. Prophylactic Therapy.

a. Therapy. prophylactic with anti-hemophiliac factors may be considered in the following situations:

▪ Patient with severe hemophilia A or B defined by a level of coagulation factor <1%.

▪ Patients with repeated episodes of bleeding, mainly in the joints. Secondary prophylaxis can be considered for 4-8 weeks.

▪ Previous prophylactic therapy and after surgery or invasive procedure for up to 14 days.

4. Anti-hemophilic factors will be available for the management of the following cases

a. Suspected bleeding in joints or muscles

b. Any injury to the head, neck, mouth or eyes or evidence of bleeding in some of these areas.

c. Unusual headache, particularly if it is followed by trauma

d. Severe pain or swelling somewhere in the body and. Any open wound that requires closure by surgical or adhesive means

f. History of an accident or trauma that may result in internal bleeding

g. Any procedure or invasive surgery

h. Persistent or profuse bleeding

i. Gastrointestinal bleeding

j. Fractures, dislocations or sprains

Refer to Table 3 for plasma factor levels and duration of replacement therapy recommended by the World Federation of Hemophilia.

Note: The calculated dose should be adjusted to the unit of the available vial and to the patient's response

Recommendations of plasma level of factor and duration of administration1

Type of Hemorrhage	Hemophilia A		Hemophilia B
Type of Hemorrhage	Desired level	Duration (Days)	Desired level	Duration (Days)
Articulate	40% - 60%	1-2, maybe more if the answer is inadequate	40% - 60%	1-2, maybe more if the answer is inadequate
Muscular (except iliopsoas)	40% - 60%	2-3, maybe more if the answer is inadequate	40% - 60%	2-3, maybe more if the answer is inadequate
Iliopsoas • Initial • Treatment	80% - 100% 30% - 60%	1-2 3-5, sometimes more as prophylaxis during physiotherapy	60% - 80% 30% - 60%	1-2 3-5, sometimes more as prophylaxis during physiotherapy
SNC / Head • Initial • Treatment	80% - 100% 50%	1-7 8-21	60% - 80% 30%	1-7 8-21
Neck and throat • Initial • Treatment	80% - 100% 50%	1-7 8-14	60% - 80% 30%	1-7 8-14
Renal	50%	3-5	40%	3-5
Deep laceration	50%	5-7	40%	5-7
Major Surgery • Preoperative • Postoperative	80% - 100% 60% - 80% 40% - 60% 30%-50%	1-3 4-6 7-14	60% - 80% 40% - 60% 30% - 50% 20%-40%	1-3 7-14
Minor Surgery • Preoperative • Postoperative	50%-80%	1-5, depending on the type of procedure	50%-80% 30%-80%	1-5, depending on the type of procedure

Policy Guidelines

Medication will be covered as per indications above.

Benefit Application

BlueCard/National Account Issues

Not applicable

Benefits are determined by the group contract, member benefit booklet, and/or individual subscriber certificate in effect at the time services were rendered. Benefit products or negotiated coverages may have all or some of the services discussed in this medical policy excluded from their coverage.

Background

Hemophilia A and B are recessive diseases linked to the X chromosome that occur in male children of female carriers. However, sometimes hemophilia must

be differentiated from other coagulation disorders when the family history is negative or unknown. The differentiation between hemophilia and other disorders,

such as some types of von Willebrand disease or acquired factor inhibitors, and the distinction between hemophilia A and B are crucial for proper management.

Hemophilia typically refers to a hereditary bleeding disorder caused by deficiency of coagulation factor VIII (hemophilia A), factor IX (hemophilia B), or factor XI

(hemophilia C)

· Hemophilia A- Inherits factor VIII deficiency (factor 8 [F8]), an X-aligned recessive disorder.

• Hemophilia B- inherits factor IX deficiency (factor 9 [F9]), also called Christmas Disease, a recessive disorder linked to the X chromosome.

• Hemophilia C-Inherits factor XI deficiency (factor II); also called Rosenthl syndrome; an autosomal recessive disorder Rarely, heterozygotes may

have bled (caused by, autosomal dominant transmission, due to heterodimer binding). Hemophilia C is especially common in Ashkenazi Jews (Jews

from Eastern Europe).

• Acquired factor deficiencies- Deficiencies of acquired clotting factors caused by an autoantibody (often with factor VIII) is sometimes referred to as

acquired hemophilia. The terms "acquired factor inhibitors" or "acquired factor deficiency" are preferable to avoid classifying the patient as having

hemophilia A or B.

• Inhibitors- In hemophilia, inhibitor refers to an autoantibody that it is usually formed in response to the infused factor. Inhibitors are more common in

people with very low baseline factor levels.

• Gravity- Hemophilia is characterized as mild, moderate or severe, based on the activity level of the residual factor or baseline (also referred to as "factor

level"); this is expressed as a percentage of normal or in international units (IU) / ml. Levels of factor normally correlate with the degree of bleeding and

symptoms present.

• Severe hemophilia- Severe hemophilia is defined as factor activity of <1 percent, which corresponds to <0.01 IU / ml /

• Modern hemophilia - Moderate hemophilia is defined as a level of factor activity> 1 percent of normal and <5 percent of normal, corresponding to> 0.1

and <0.05 IU / ml.

• Mild hemophilia - Mild hemophilia is defined as a factor activity level> 5 percent of normal and <40 percent normal (> 0.05 and <0.40 IU / ml.

Epidemiology

Hemophilia A is more common than hemophilia B. Hemophilia A is also more likely to be serious.

• Hemophilia A- Hemophilia A occurs in approximately 1 in 5,000 live-born males. Approximately two thirds have severe disease (ie, factor IX activity <1

percent of normal).

Severe hemophilia is almost exclusively a disease of men, although women may be affected in some rare cases (eg, compound heterozygosity, skewed

lionization, loss of X chromosome). In contrast, mild hemophilia has been described in up to a quarter of the carrier women who are heterozygous.

Hemophilia occurs in all ethnic groups and throughout the world. A publication of the World Hemophilia Foundation estimates that 43 percent of the population

with hemophilia in the world lives in India, Bangladesh, Indonesia, and China, of which only 12 percent have been diagnosed [4].

Clinical manifestations

The clinical manifestations of hemophilia are related to bleeding, problems with haemostasis, sequelae of hemorrhage, or complications of coagulation factor

infusion.

Bleeding sites

Intracranial hemorrhage - intracranial hemorrhage (ICH) is relatively rare compared to other sites of bleeding, but it is one of the most dangerous and life-

threatening events in people with hemophilia [24].

The joints and muscles. Hemarthrosis (ie, bleeding in a joint) is the most common site of bleeding in outpatients, accounting for up to 80 percent of bleeding

[29,30]. Spontaneous hemarthrosis are characteristic of severe disease. Bleeding in the joint cavity originates in the synovial vessels.

Epistaxis, oral bleeding, gastrointestinal. Bleeding can occur from numerous sites of the pharynx gold, such as the nose, oral mucosa, and gum; Sometimes

this type of bleeding follows minor trauma or dental procedures. In addition, coughing or vomiting can produce hemorrhage in the posterior pharynx, which can

lead to compromising air life or airway obstruction.

Genitourinary tract. Hematuria is a frequent manifestation of severe hemophilia; It is usually benign and is not associated with progressive loss of kidney f

unction. Bleeding can come from the kidneys or the bladder and may persist for days or weeks. Urethral obstruction with colic may occur when clots form.

Other etiologies should be excluded if a particular episode is associated with pain or is not sensitive to therapeutic intervention.

Development of inhibitors

An important complication in patients with severe hemophilia A is the development of autoantibodies that block the activity of the relevant factor (ie, inhibitors).

These inhibitory antibodies develop in response to the exogenous factor; occur in approximately 25 percent of patients with severe hemophilia A and 3 to 5

percent with severe hemophilia B. Inhibitors are much less common in patients with mild or moderate disease, presumably because the infusion factor is not as

likely to be recognized as a foreign protein in these individuals. Inhibitors complicate episodes of bleeding, since they diminish the response capacity to factor

infusions; In addition, anaphylactic reactions can occur with factor IX inhibitors.

Management of bleeding or surgery in a patient with an inhibitor (neutralizing alloantibody against infused factor) is especially challenging because inhibitors bind to the infused

factor and render it ineffective. Inhibitors are much more likely to occur in individuals with hemophilia A and those with severe disease. Some patients may only become aware

that they have an inhibitor in the midst of an acute bleeding episode or surgery, when factor infusions no longer raise factor activity levels to the expected range or if there is an

allergic/anaphylactic reaction to the infusion.

Bypassing products (rFVIIa or FEIBA) — A bypassing product is generally the first choice in a patient with hemophilia A or B who has a high titer inhibitor and requires treatment

for bleeding or surgery. These clotting factor products contain an activated form of a downstream clotting factor in the coagulation cascade. Activated factor VII (factor VIIa) can

directly activate factor X, bypassing the need for factors VIII and IX. Available products include recombinant activated factor VII (rFVIIa; NovoSeven, NovoSeven RT) and

activated prothrombin complex concentrates (aPCCs) such as FEIBA (factor eight inhibitor bypassing agent; the only aPCC available in most settings)

Both rFVIIa and FEIBA contain activated clotting factors and both are effective for hemostasis in hemophilia. For hemophilia B with an inhibitor, rFVIIa is the preferred agent

because it does not contain factor IX; this is especially true in individuals with hemophilia B with an inhibitor who have experienced reactions or anaphylaxis upon exposure to

factor IX. For hemophilia A, either product can be used. If the patient has had a favorable response with one of these products, it is reasonable to use the same product again.

●rFVIIa – Dosing of rFVIIa is typically 90 to 120 mcg/kg (rounded to the nearest vial size) every two to three hours until hemostasis is achieved and at three- to six-hour

intervals after hemostasis has been restored .

●FEIBA – Dosing of FEIBA is typically 50 to 100 units/kg every 6 to 12 hours, not to exceed 100 units/kg/dose or 200 units/kg/day

Regulatory Status

Not applicable

Rationale

Promotion of greater diversity and inclusion in clinical research of historically marginalized groups (e.g., People of Color [African-American, Asian, Black, Latino and Native American]; LGBTQIA (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, Asexual); Women; and People with Disabilities [Physical and Invisible]) allows policy populations to be more reflective of and findings more applicable to our diverse members. While we also strive to use inclusive language related to these groups in our policies, use of gender-specific nouns (e.g., women, men, sisters, etc.) will continue when reflective of language used in publications describing study populations.

Population Reference No. 1 Policy Statement

For individuals with treatment of classic type A hemophilia, including perioperative management. Interventions of interest: Antihemophilic factor derived from human plasma, Monoclate-P, Koate-DVI. Comparators of interest are: Standard treatment without management of antihemophilic factors. Relevant outcome includes: Overall survival, Change in disease status, Quality of life, Treatment related morbidity. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Population Reference No. 1 Policy Statement

[ x ] MedicallyNecessary

[ ] Investigational