What is Hemophilia?Hemophilia is a rare bleeding disorder that results from reduced levels or lack of clotting factor VIII

(FVIII; hemophilia A) or IX (FIX; hemophilia B). Normal blood clotting is a complex process that involves

as many as 20 blood proteins called clotting factors. The shortage or absence of one of these factors,

as happens in hemophilia, may disrupt the clotting process. Persons with hemophilia cannot form

blood clots when needed to stop bleeding and therefore bleed longer than people without hemophilia,

not faster. People with hemophilia experience abnormal bleeding – either after an injury or

spontaneously-into their joints, muscles, and soft tissues. Bleeding into the joints and muscles is one of

the distinctive signs of hemophilia. Minor cuts and scrapes are often not of great concern for people

with hemophilia, but bleeding into the head, abdomen, kidneys, intestines, and major joints and

muscle groups can be life- or limb-threatening.Types of HemophiliaThe two most common types of hemophilia are FVIII deficiency (hemophilia A) and FIX deficiency

(hemophilia B, or Christmas disease). According to the National Institutes of Health (NIH), both types

of hemophilia are considered rare diseases, that is, they each affect fewer than 200,000 individuals in

the United States.1 Both hemophilia A and B affect all races and ethnic groups equally. 2,3

Hemophilia A (FVIII deficiency)2: Hemophilia A is the most common type of hemophilia. It occurs in

about one in 5,000 male births and affects about 25,000 individuals in the United States.

Hemophilia B (FIX deficiency)3: Hemophilia B is the second most common type of hemophilia and is

less common than FVIII deficiency. Hemophilia B occurs in about one in 25,000 male births and affects

about 3,300 people in the United States.

Hemophilia C (Factor XI deficiency): A Unique Bleeding Disorder

Factor VIII and Factor IX deficiencies are the best known and most common types of hemophilia, but

other clotting factor deficiencies also exist. Low levels of factor XI (FXI), another blood protein required

for clot formation, cause hemophilia C, which is also known as plasma thromboplastin antecedent

(PTA) deficiency or Rosenthal syndrome. Although also associated with bleeding, hemophilia C differs

from hemophilia A and B in incidence, cause, bleeding tendency, and treatment. For more detailed

information on hemophilia C, including treatment options and complications, click here.

The remainder of the hemophilia section will focus on hemophilia A and B.Severity of Hemophilia A and BHemophilia is classified as mild, moderate, or severe depending on the amount of the clotting factor in

a person’s blood.2,3 The normal range of FVIII and FIX is between 50% and 150%. Hemophilia severity

is classified as follows:

Severity Blood clotting factor level

Normal 50%-150%

Mild hemophilia 6%-49%

Moderate hemophilia 1%-5%

Severe hemophilia <1%

In mild hemophilia (6% to 49% factor activity), bleeding typically occurs only after injury, trauma, or

surgery. Patients may have very few symptoms otherwise. About 25% of the hemophilia population has mild

deficiency.

In moderate hemophilia (1% to 5% factor activity), bleeding tends to occur after minor injuries, though

spontaneous bleeding episodes (i.e., without obvious cause) may occur. About 15% of the hemophilia

population has moderate deficiency.

Persons with severe hemophilia (<1% factor activity) may experience not only bleeding after injury, trauma,

or surgery, but also spontaneous bleeding into joints and muscles. Recurrent bleeding into joints can cause

hemophilic arthropathy, a joint disease that results in physical disability at a young age. About 60% of the

hemophilia population has severe factor deficiency.

Causes of HemophiliaHemophilia is a genetic disease and is caused by a mutation within the genes for coagulation factors

VIII or IX. In approximately 70% of cases, hemophilia is inherited from a parent, but in about 30% of

patients, the family history may be absent or may not be apparent. In such cases, the condition is

often caused by a spontaneous gene mutation at the time of fertilization.2,3

The gene causing hemophilia normally contains the instructions for the body to make clotting factor.

This gene is carried on the X chromosome, which is called a sex chromosome. A person’s gender is

determined by the pairing of two sex chromosomes (X and Y) inherited from their parents. Males have

an XY pairing with one X chromosome inherited from the mother and one Y chromosome inherited

from the father. Females have an XX pairing with one X chromosome inherited from the mother and

one from the father. Men who have hemophilia will pass their Y chromosome to their sons and their X

chromosome (with the altered gene) to their daughters. Sons, therefore, will not be affected by the

father’s altered gene, but daughters will all be carriers (also known as obligate carriers), because

they carry their father’s altered X chromosome.

Women carriers have one X chromosome with the altered gene and one chromosome with a properly

functioning gene. If a male child inherits his mother’s unaffected chromosome, he will not have

hemophilia. If, however, he inherits his mother’s affected X chromosome, he will have hemophilia. If a

female child inherits her mother’s affected X chromosome, she will be a carrier. As such, there is a

50% chance that a female carrier’s sons (XY) will have hemophilia (Figure 1).

Figure 1: Hemophilia Inheritance – Carrier Mother and Father without Hemophilia4

Figure 2: Hemophilia Inheritance – Father with Hemophilia and Mother Who is Not a

Carrier4

Image from: Darling D, ed. “hemophilia.” The Internet Encyclopedia of Science. (Accessed December

29, 2009 at http://www.daviddarling.info/encyclopedia/H/hemophilia.html). Images used with

permission.Important Information for Female Carries of HemophiliaA carrier of the hemophilia trait can pass on the trait to her children but usually does not experience

any symptoms herself. A woman is an obligate carrier of hemophilia if any of the following apply:

She is the biological daughter of a man who has hemophilia,

She is the biological mother of more than one son with hemophilia, or

She is the biological mother of at least one son with hemophilia and has at least one other blood relative

with the disorder.

It is recommended that women who are carriers or are at risk of being carriers have their clotting

factor levels evaluated. This evaluation is available at the IHTC.

Women with HemophiliaAs an X-linked recessive trait, hemophilia occurs almost exclusively in males. There are circumstances,

however, when females can experience bleeding symptoms.

1. Symptomatic carriers: In some cases, female carriers of hemophilia can have low (< 50%) levels of either

FVIII or FIX and experience bleeding symptoms. Female carriers who have bleeding symptoms are called

symptomatic carriers.

2. Daughters of a father with hemophilia and a carrier mother: In rare cases, it is possible for a female to

have a father with hemophilia and a mother who is a carrier, and thereby inherit an affected X chromosome

from both parents. Such daughters would therefore have hemophilia.

3. Turner’s syndrome: This is a rare chromosomal disorder in which females carry only one X chromosome. If

these girls inherit the hemophilia gene, they will have hemophilia.

Signs & Symptoms of HemophiliaThe primary signs and symptoms of hemophilia are excessive/prolonged bleeding and easy

bruising.5 Bleeding can be external or internal. The extent of these symptoms depends on the

hemophilia type (A or B) and severity (mild, moderate, or severe).

Persons with mild hemophilia (<6% – 49% factor level) may have excessive bleeding after dental

procedures, accidents, or surgery, but do not typically have spontaneous bleeds as in severe hemophilia. In

some cases, mild hemophilia causes so few symptoms that it is not diagnosed until adolescence or

adulthood.

Moderate and severe hemophilia are typically characterized by more frequent and severe bleeding

complications as compared to mild hemophilia.

Males with severe hemophilia may bleed heavily after circumcision. In many cases where there is not a

family history of hemophilia, the diagnosis is made due to excessive or prolonged bleeding after

circumcision.

Other common symptoms include the following:

Joint bleeding;

Soft tissue bleeding or bleeding after minor trauma;

Easy or excessive bruising;

Prolonged bleeding in the mouth from a cut or bite;

Bleeding associated with surgery or invasive procedures

Emergency CareRarely patients can have bleeding within vital internal organs or structures. These are often life-

threatening bleeding events. Symptoms of such internal bleeding can be difficult to recognize, so

it is important that patients know what to look for. The four most serious bleed sites include6:

Head – headache, neck pain, sleepiness, sensitivity to light, nausea, vomiting, loss of consciousness.

There might also be no initial symptoms of a head bleed, so PATIENTS MUST CONTACT THE HTC

IMMEDIATELY IF EVEN MINOR HEAD TRAUMA OCCURS.

Neck/tongue – neck-swelling or tongue-swelling that may cause blockage of the airway and problems

with breathing.

Spinal cord – weakness, tingling, or pain in the arms or legs; difficulty with urination or bowel movements;

back pain.

Internal organs such as stomach, liver, spleen, intestine – blood in vomit, vomit that looks

like coffee grounds, black tar-colored stools.

If you or your family member needs to visit the emergency department (ED), be sure to contact the

IHTC so we can help you get the best possible care. Visit our webpage on Emergency Care to learn

about what you should do, what you need to take to the ED, and what information you need to provide

to the ED staff. Read the useful IHTC’s Emergency Care Tips and keep it handy.Joint Bleeds

Joint bleeds (called hemarthroses), which can be spontaneous or caused by trauma, are the main

cause of chronic pain and disability in severe hemophilia.7 Chronic bleeding into the joints breaks down

the joint lining (synovium) and causes joint damage. This results in the painful arthritic condition

known as hemophilic arthropathy. Joint bleeds most often occur in the knees, elbows, ankles, or

hips, but can occur in any joint. While joint bleeds can occur in all severities of

hemophilia, spontaneous joint bleeds tend to be most common in individuals with severe

hemophilia. In individuals with moderate and especially with mild hemophilia, trauma or

injury usually initiates joint bleeding.

Symptoms of joint bleeds are not always apparent right away. The first symptom is often tingling or

tightness in the joint with no real pain or visible signs of bleeding. As bleeding continues, the joint

swells and becomes warm to touch and painful to move. Swelling increases as bleeding continues and

movement can be temporarily lost. Pain can be severe. Joint bleeds must be treated quickly and

aggressively to prevent permanent joint damage. Untreated joint bleeds can be debilitating, as chronic

pain, swelling, and permanent joint damage lead to limited mobility and decreased quality of life.

Soft Tissue BleedingBleeding in muscular tissue is also called soft tissue bleeding. Bleeding in large muscle groups such as

the hip flexors (iliopsoas muscle) can cause severe anemia and unstable blood pressure. Bleeding

within compartments such as the forearm or lower extremity can cause compartment syndrome.

Patients with compartment syndrome often have significant nerve and tissue damage with symptoms

of pain, tingling or numbness. Compartment syndrome requires immediate specific treatment to

control bleeding and, in some cases, measures to reduce the pressure on nerves and blood vessels.Diagnosis of HemophiliaThe diagnosis of hemophilia is made with attention to the following:

1. Personal history of bleeding

2. Family history of bleeding and its inheritance pattern

3. Laboratory testing

The details about personal and family history of bleeding were discussed in earlier sections.Laboratory EvaluationIn a patient with suspected hemophilia, screening coagulation tests along with mixing studies are

performed. Once the diagnosis of hemophilia is established, the screening of other at-risk family

members, including females, should be performed to diagnose other affected individuals and

determine the clotting factor level of carriers.

Genetic testing is available to identify the genetic change causing hemophilia. Genetic tests are

particularly helpful in diagnosing the carriers in the family as they often do not experience symptoms

and may have normal levels of the clotting factor.

Diagnosis of Hemophilia in Newborns

In newborns who experience bleeding from heel sticks, bruises or bleeding after an intramuscular

injection, bleeding with circumcision, head bleeds, or bruising, diagnostic tests are needed. FVIII

deficiency or hemophilia A can be diagnosed at birth because newborns should have normal levels of

FVIII. In contrast, FIX levels are low during the newborn period and may take 6 months to reach normal

levels. The diagnosis of mild FIX deficient hemophilia, therefore, may be more difficult in the newborn

period, depending on the level of deficiency. It is often prudent to recheck the FIX values when the

baby is 3 to 6 months old to confirm a diagnosis of mild hemophilia A or B. Until then, an infant with

suspected hemophilia should be treated as if he did have hemophilia. Alternatively, genetic testing

may be performed to confirm the diagnosis of hemophilia. The IHTC staff can advise physicians on

which tests to order and how to interpret the results, especially for patients who are experiencing or

have a history of abnormal bleeding.

The IHTC provides a cord blood kit to diagnose hemophilia in newborns in families with known

hemophilia. If the blood testing is performed on umbilical blood, care should be taken to avoid

contamination with maternal blood. Cord blood testing may not always be accurate in mild hemophilia.

Prenatal diagnosis options

The following prenatal diagnosis options are available for women known to be carriers of hemophilia:

Noninvasive fetal sex determination by ultrasound. Fetal sex determination provides information about the

potential to have an affected male and may be helpful in making informed decisions about delivery.

Invasive testing by chorionic villus sampling or amniocentesis. This testing provides definitive diagnosis of

an at-risk fetus.

Treatment of HemophiliaThere is currently no cure for hemophilia. However, treatment has advanced remarkably in the past 30

years. Children with hemophilia who receive comprehensive treatment can now look forward to a near-

normal life expectancy.8

For individuals with mild hemophilia A, the Medical and Scientific Advisory Council (MASAC) of the

National Hemophilia Foundation recommends that desmopressin (DDAVP) should be used whenever

possible. DDAVP is available in both an injectable form (DDAVP Injection) and as a highly concentrated

nasal spray (Stimate Nasal Spray). Click here to download the IHTC’s fluid restriction guidelines and

other information on DDAVP/Stimate use. Desmopressin should not be used in some categories of

patients. Children under the age of 2 years, pregnant women, and patients with mild hemophilia A in

whom desmopressin does not provide adequate Factor VIII levels should be treated with factor

concentrates.

Hemophilia can also be well managed with infusion of manufactured clotting factor concentrates to

replace the factor that is missing from the blood. This is called clotting factor replacement therapy.Clotting Factor ConcentratesClotting factor concentrates can be made using human plasma or through recombinant technology.

1. Plasma-derived products: plasma-derived products are made from human blood components such as

donated plasma.

2. Recombinant products: recombinant factor products are made in a laboratory using recombinant

technology. These products do not use human blood as a starting component. Recombinant products offer a

safer option than plasma-derived products because they avoid potential blood-borne transmission of

infectious diseases. In the United States, treatment with recombinant products, when available, is the

standard of care.

Clotting factor is administered by placing a needle in the patient’s vein (venipuncture) or through a

surgically implanted device called a Port-a-Cath (“port”). Treatment (“infusion”) with clotting factor

stops or prevents bleeds by raising the patient’s factor level for a certain time period. Patients who

need frequent infusions and their parents often learn to infuse at home, making treatment more

convenient and accessible for the patient and family. IHTC nurses are experienced in training families

and patients to home infuse.

Patients usually receive clotting factor products from homecare companies or HTC pharmacy

programs. As Indiana’s only federally recognized comprehensive treatment center, the IHTC operates a

Public Health Service 340B Pharmacy Program. This program allows the IHTC to dispense factor at

reduced prices. Visit the IHTC Pharmacy Program to learn more about how IHTC’s pharmacy program

works on behalf of patients to lower costs and optimize the care those patients receive.

Patient Notification System

The IHTC encourages you to register with the Patient Notification System. This free, confidential, 24

hour communication system provides information on withdrawals and recalls of plasma-derived and

recombinant therapies. To learn more about what this system is and how to register for this

service, click here.Hemophilia Treatment RegimensThe amount of factor and the frequency of administration depend on several variables including

bleeding severity and site; and the patient’s size (i.e., weight). There are two main categories of

treatment for hemophilia.

Prophylactic Infusion Therapy (Prophylaxis)

The Medical and Scientific Advisory Committee (MASAC) of the National Hemophilia Foundation and

the World Health Organization (WHO) recommend prophylactic (preventive) treatment for persons with

severe hemophilia A or B.9 10 Prophylactic therapy often involves regular administration of clotting

factor 2 to 3 times per week to raise the factor level to a moderate range to preventspontaneous

bleeds or bleeds after minor injury. Prophylactic treatment requires a large amount of factor and

frequent infusions. Due to the high cost of prophylaxis, health insurance coverage is vital for patients

who use this treatment. The IHTC social worker is available to answer your questions about insurance

and to help you through changes in your insurance coverage. To learn more about the types of

prophylactic treatments and IHTC’s prophylaxis clinic, click here.

Episodic Infusion Therapy (“On-Demand”)

Episodic treatment of hemophilia involves the use of clotting factor to treat acute bleeds after bleeding

has started. In general, people with mild and moderate hemophilia, who tend to bleed less often, use

episodic treatment.

Treatment Records Help You Take Charge of Your Health Care!

By keeping treatment records, you can take charge of your health care and help the IHTC provide the

best care for you.

What is a treatment record?

A treatment record or infusion log is a way to document or record bleeding episodes and treatment in

an organized manner. This record or log makes it easier to discuss health issues with your nurse and

physician in clinic or when you have a concern.

Why do I need to keep an infusion log?

Keeping a treatment log maintains an accurate record of your bleeding episodes and treatment over a

period of time. Trying to recall bleeding events and treatment is difficult and often inaccurate. Having

accurate information available assists in the discussion and development of the best treatment plan

for you. Additionally, many insurance companies now require treatment records of every bleeding

episode and infusion for continued coverage of factor concentrate.

What are my options?

The IHTC currently has two recording options available. We would be happy to discuss either of these

options with you further.

1. ATHNadvoy: This electronic treatment record system enables you to log bleeding events and treatments

online through a computer. Click here to learn more about ATHNadvoy and how to register for this service.

2. Infusion calendar: This paper calendar is specifically designed by the IHTC team to document bleeding

episodes and infusions in an easy to document and read format. Click here to download the IHTC’s

instructions on how to use the infusion calendar.

Is keeping a treatment record a requirement for my care?

We recommend that everyone record their bleeding events and infusions to help the IHTC provide the

best care possible. In addition, many insurance agencies now require these records.

What happens to the records when I send them to the IHTC?

Your treatment records will become a part of your medical record and can be accessed and viewed by

the IHTC staff, or requested by you when you need them.

Treatment Adherence in Hemophilia CareThe success of hemophilia treatment depends on two important factors: the doctor prescribing the

right treatment plan for the patient and the patient following the treatment plan. Treatment

adherence describes how well a patient sticks to medical or health advice he has been given.

Because hemophilia requires patients to do a lot of self-care at home, patients must be actively

involved with doctors to manage the treatment.

Not following a hemophilia treatment plan may cause the treatment not to work, which could lead to

disability and poor quality of life . If a patient does not treat bleeds as prescribed, the bleeds may last

longer, keep recurring in the same joint, and cause severe joint damage and disability. These are the

painful outcomes that prophylaxis is meant to prevent. Because factor is expensive, it is especially

important for patients to follow a treatment plan to prevent wasting a valuable medical resource.

Most hemophilia doctors agree that treatment adherence is important for patients to have the

best health possible. Until now, however, there has not been a good way to measure treatment

adherence in hemophilia. Studies have looked at infusion logs, pharmacy records, range of motion,

and patient interviews to measure adherence, but none of these studies created a standard way to

measure how well a patient follows a treatment plan. To meet the need for a standard way to measure

adherence, the IHTC developed two scales – the Validated

Hemophilia Regimen Treatment Adherence Scales (VERITAS) for episodic treatment (VERITAS-PRN)

and for prophylactic treatment (VERITAS-Pro). These scales were validated to show that they in fact do

measure treatment adherence. Hemophilia providers can now use the VERITAS tools to check

adherence in patients and to help patients achieve the best health possible.VERITAS: IHTC’s Validated Treatment Adherence ScalesEach VERITAS survey has 24 questions on six 4-question subscales. The subscales check different

areas of adherence, like the dose and time of infusions, whether a patient forgets or skips infusions,

and the patient’s communication with the HTC. By checking multiple areas of adherence, providers

can identify areas that the patient may be able to strengthen. This helps the patient get the best

health outcomes possible.

Validating the scales involved testing them in patient groups. We showed that the scales reliably

measure adherence and are a valuable tool for patient care. The scales take less than ten minutes to

complete and can be added to a clinic visit.

Both scales were published in 2010 in Haemophilia, a leading medical journal.11,12 The hemophilia

community is excited about the scales. We have presented the scales at the American Society of

Hematology, World Federation of Hemophilia, International Network for Pediatric Hemophilia, and the

first Conference on Blood Disorders in Public Health. The VERITAS-Pro is being translated into Spanish,

Italian, and French. It has been used in clinic settings and added to several drug studies. We hope that

the VERITAS scales will improve our understanding of the link between treatment adherence and

patient health, and increase our ability to help patients achieve the best health possible.

Please use the following links to read the VERITAS study abstracts.

VERITAS-PRN – Episodic treatment adherence scale

VERITAS-PRO – Prophylactic treatment adherence scale

For additional information about the tools themselves and about licensing the scales for use in

research and clinical practice, please contact Natalie A. Duncan, MPH, at the IHTC at 1 317 871 0011

(ext. 273) or nduncan@ihtc.org.Hemophilia Treatment Centers (HTC’s) and Comprehensive CareThe federal Office of Maternal and Child Health and the Centers for Disease Control and Prevention

(CDC) support a network of specialized healthcare centers dedicated to treating blood

disorders.13 Currently, the network includes about 140 HTCs, eight hemostasis and thrombosis centers,

and seven thalassemia care centers. The purpose of federally recognized HTCs is to prevent and

reduce problems related to blood disorders by providing optimal and comprehensive care.

The IHTC is Indiana’s only federally recognized HTC and provides comprehensive care for

individuals with bleeding and clotting disorders. In addition, the IHTC’s multidisciplinary team also

cares for individuals with sickle cell disease and other hemoglobin disorders.

What is Comprehensive Care?

The comprehensive care provided at HTCs involves multidisciplinary clinic teams, research

initiatives, and outreach and education programs. The multidisciplinary team may include:

adult and pediatric hematologists

triage and clinic nurses

social workers and other mental health professionals

dental hygienists

physical therapists

coagulation laboratory personnel

research coordinators

The team works closely with local healthcare providers to meet the specific needs of the population to

improve their quality of life. The care provided at HTCs has been shown to significantly reduce

complications for persons with hemophilia. Mortality rates are 40% lower in persons who use HTCs

than in those who do not, despite the fact that the more severely affected patients are the ones who

typically visit these centers.14 HTCs place a premium on preventive care because of the difficulty and

expense of treating the complications of hemophilia, which can reduce the patients’ quality of life.

The IHTC exceeds national staffing standards and offers an extensive spectrum of care through

dedicated trained professionals. In addition to the core services provided at all HTCs (e.g.,

hematologists, clinical nurses, social workers, physiotherapists), the IHTC staffalso includes a career

counselor, risk reduction specialists, a registered dietitian, clinical research professionals, genetic

counselor, and dental hygienist.

For more about the value of comprehensive care, visit IHTC’s webpage on comprehensive care or go to

our Reading Room for IHTC’s informational brochure, “Why Attend Comprehensive Clinic?“.Outreach Comprehensive Clinic

To provide comprehensive care to all Hoosiers with bleeding disorders, the Indiana Hemophilia &

Thrombosis Center Inc. (IHTC) conducts a series of outreach comprehensive clinics throughout Indiana

each year. The IHTC’s outreach programs are state and federally funded, so there is no charge to

patients for the team’s evaluation. However, patients or their insurers are responsible for costs

associated with laboratory tests and radiological evaluations. To learn more about IHTC’s outreach

comprehensive clinic and to see the dates and locations of our outreach clinics in 2010, click here.Special ConsiderationsAvailability and Cost of Hemophilia TreatmentTreatment with clotting factor is expensive and accounts for up to 90% of the costs of hemophilia

care.15, 16 Yearly cost of care has been estimated to range from about $19,000 in persons with mild or

moderate hemophilia to $300,000 in persons with severe hemophilia.16,17 When complications and/or

co-existing illnesses are present, the cost of care easily exceeds this range.Insurance IssuesThe high cost of care can lead to trouble in getting health insurance and paying for care. IHTC social

workers are knowledgeable about insurance options and are here to help ensure that patients have

continued access to optimal care. IHTC’s Pharmacy Program helps patients enroll in patient assistance

programs so patients have access to clotting factor during lapses in insurance coverage.Dental CareGood dental hygiene is important for all individuals, including those with bleeding disorders. However,

individuals with bleeding disorders need to take some special precautions in preparing for dental

procedures as well as in providing essential information to the dental care provider to ensure the best

outcomes for both the procedure and long-term dental health. Visit IHTC’s webpage on dental care to

learn more about the special considerations for dental care in individuals with bleeding disorders.

Inhibitor DevelopmentOne of the most serious complications in hemophilia treatment is the development of an inhibitor, an

antibody against the clotting factor used to treat hemophilia. The body’s immune system produces

antibodies to destroy substances that the immune system does not recognize. Because persons with

hemophilia are deficient or lacking in a specific clotting factor protein, replacing the clotting factor can

result in an immune response. This happens when the body identifies the clotting factor as “non-self”

or foreign and destroys it. Up to 30% of people with severe or moderate FVIII deficiency and 1% to 6%

of people with severe FIX deficiency develop inhibitors.18

The presence of inhibitors complicates treatment of hemophilia because it reduces or eliminates the

effectiveness of treatment with clotting factor. In cases of low-titer inhibitors, higher-than-usual doses

of clotting factor may be effective treatment. In persons with high-titer inhibitors, use of clotting factor

replacement is not possible and so-called bypassing agents may be used. These agents are believed to

“bypass” the need for FVIII and FIX to form stable clots. Bypassing agents such as prothrombin

complex concentrate (PCC), activated PCC (aPCC), and recombinant activated FVII (rFVIIa) are used to

stop the bleeding.Immune Tolerance InductionImmune tolerance induction (ITI) is an intensive treatment that aims to reduce or eliminate inhibitors

against clotting factor. This treatment involves regular use of clotting factor and/or immunomodulating

agents to make the immune system “tolerate” the clotting factor. In other words, the aim of ITI is to

stop the immune system from treating the infused factor as “foreign.” ITI regimens require

commitment from the patient and family as some regimens use infusion as often as twice per day.19

Because inhibitors reduce the effectiveness of treatment with clotting factor and complicate care, they

greatly increase the cost of care. Most of the increased expenses are related to the high cost of

bypassing agents and ITI regimens. It has been estimated that in patients with FVIII inhibitors with

unfavorable prognosis, there is an 8-fold increase in FVIII consumption and cost of care.20

Immune Tolerance Clinic

At the IHTC, a physician and nurse run the immune tolerance clinic to help patients with their immune

tolerance treatments. Click hereto find out more about the services provided through the immune

tolerance clinic.

Co-existing IllnessesThanks to significant improvements in treatment and prevention of bleeds, the life expectancy of

people with hemophilia is now approaching that of the general population. As a result, individuals with

hemophilia are now having other illnesses linked not only with hemophilia, but also with aging, such as

heart disease. The older generation with hemophilia presents new challenges to providers at HTCs and

other healthcare professionals. Patients’ physicians must take a holistic, coordinated approach to care.

In the aging population, illnesses related to hemophilia may include:

Hemophilic arthropathy symptoms such as chronic pain and reduced bone mineral density. Patients may

need physical therapy, rehabilitation, and/or orthopedic surgery. These individuals may be at greater risk for

injuries linked to balance dysfunctions and associated increased risk of falls.

Chronic hepatitis C, primary liver cancer, and end-stage liver disease.

HIV and complications related to treatment with HAART (highly activated antiretroviral therapy).

Inhibitor development, especially in elderly patients with mild hemophilia who have not been exposed to

clotting factor products in the past.

Kidney abnormalities

Co-existing illnesses not related to hemophilia may include:

Overweight/obesity

Diabetes

Heart disease

High blood pressure

Cancers

Dental problems that need surgical extraction

Erectile difficulty and sexual problems

Because co-existing illnesses in aging individuals with hemophilia may need complex treatments,

coordination of care among various providers is essential. The IHTC works closely with other

healthcare professionals to provide the best care for individuals with bleeding disorders and their

families.Blood Product Safety

Thanks to improved blood screening, testing, viral inactivation and removal methods, and the

development of recombinant factor products, today’s factor products are much safer than those of the

past. While there have been no recent cases of transmission of dangerous bacteria or viruses,

transmission of hepatitis A, hepatitis C, and other blood-borne diseases is now only a small risk for

people treated with human plasma-derived products. No vaccination currently exists for hepatitis C,

but hepatitis A and B vaccines are recommended for all hemophilia patients, regardless of their type of

factor product.

At the IHTC, our risk reduction specialist can help explain to patients and their families the steps they

should take to prevent or reduce any complications related to bleeding disorders.Preventive CareIndividuals with hemophilia can take measures to stay in good health and to prevent poor outcomes

linked with the diagnosis. Patients are advised to:

Stay up-to-date on vaccinations

Attend annual comprehensive clinic evaluations

Avoid situations and high-risk activities that may cause bleeds

Maintain good oral hygiene (to prevent extensive dental procedures)

Exercise regularly and maintain a healthy body weight

Identify and treat bleeds promptly, as directed by the hematologist

Carrier Testing for WomenCarrier testing is available to find out whether females with a family history of hemophilia are carriers.

Genetic testing is the most accurate method of carrier testing. It involves taking a blood sample to look

for the specific alteration in the FVIII or FIX gene that caused hemophilia. Carrier testing using factor

levels is not 100% accurate as some women carriers can have normal factor levels and may be

classified as “non-carriers” if tested with factor levels. This inaccurate information can result in medical

errors.Steps to Take for Carrier TestingWomen should talk to their doctors and meet with a genetic counselor to discuss carrier testing and

their options. They may contact the IHTC at 317-871–0000 or toll–free at (877) 256-8837 to speak

to the center’s genetic counselor. IHTC also encourages women to talk with their families to find out

what type of hemophilia (A or B) is present, the severity (mild, moderate or severe) and whether

anyone has had genetic testing done.

References

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3. National Hemophilia Foundation. Hemophilia B (Factor IX Deficiency), 2006. Available

at:http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?

menuid=181&contentid=46&rptname=bleeding (Accessed December 18, 2009)

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