The Power of Your Choice
Your choice of the IHTC Pharmacy Program directly supports your IHTC team and patient services, and activities provided to the hemophilia community. The IHTC Pharmacy Program provides savings to you and your health insurance plan.
Every patient has the right to choose their clotting factor pharmacy provider. The IHTC supports your right of choice and will assist you in making an informed decision.
Hemophilia A and B
- What is Hemophilia?
- Causes of Hemophilia
- Signs & Symptoms of Hemophilia
- Treatment of Hemophilia
- Treatment Adherence in Hemophilia Care
- Hemophilia Treatment Centers (HTCs) and Comprehensive Care
- Special Considerations
- What Can IHTC Do For You?
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 Hemophilia
The 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 B
Hemophilia 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|
- 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 Hemophilia
Hemophilia 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
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. Males with hemophilia cannot pass the condition onto their sons, but all of their
daughterswill be carriers (Figure 2).
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 Hemophilia
A 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 Hemophilia
As an X-linked recessive trait, hemophilia occurs almost exclusively in males. There are circumstances, however, when females can experience bleeding symptoms.
- 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.
- 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.
- 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 Hemophilia
The 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
Rarely 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 (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 Bleeding
Bleeding 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 Hemophilia
The diagnosis of hemophilia is made with attention to the following:
- Personal history of bleeding
- Family history of bleeding and its inheritance pattern
- Laboratory testing
The details about personal and family history of bleeding were discussed in earlier sections.
In 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 Hemophilia
There 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 Concentrates
Clotting factor concentrates can be made using human plasma or through recombinant technology.
- Plasma-derived products: plasma-derived products are made from human blood components such as donated plasma.
- 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 Regimens
The 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 prevent spontaneous 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.
- 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.
- 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 Care
The 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 Scales
Each 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 email@example.com.
Hemophilia Treatment Centers (HTC’s) and Comprehensive Care
The 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 staff also 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.
Availability and Cost of Hemophilia Treatment
Treatment 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.
The 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.
Good 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.
One 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 Induction
Immune 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 here to find out more about the services provided through the immune tolerance clinic.
Thanks 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:
- Heart disease
- High blood pressure
- Dental problems that need surgical extraction
- Erectile difficulty and sexual problems
Screening for Heart Disease
A study by the IHTC and other earlier studies showed that people with hemophilia appear to have the same risk of developing heart disease as the general population, based on various risk factors. Moreover, the use of factor concentrates and infection with HIV also may play a role in the occurrence of heart disease in people with hemophilia. It is therefore reasonable to screen for heart disease and its risk factors in individuals with hemophilia. The IHTC’s newsletter for medical care providers explains the routine screening and evaluations providers should order to screen for heart disease.
Screening for Liver Disease
Older patients with hemophilia may have been transfused with blood products before 1992, which could have exposed them to viral hepatitis. Thus, if not documented, they should be appropriately screened for viral hepatitis (hepatitis B and C) based on their past exposure to blood products. Screening for liver disease should be performed as part of a thorough medical evaluation.
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.
Individuals 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 Women
Carrier 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 Testing
Women 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. Women who are pregnant or planning a pregnancy and have a family history of hemophilia should be aware of the following information:
- Their likelihood of having a child with hemophilia;
- Testing is available to determine carrier status and therefore the chances of having a child with hemophilia;
- Prenatal testing may be available to find out whether a male fetus has hemophilia;
- Carrier testing may help to make family planning decisions, allows for prenatal diagnosis if desired, and may indicate precautions to be taken when the child is born.
In women who are or may be carriers of hemophilia, difficult delivery (for instance, prolonged second stage of labor, using forceps) should be avoided. A male baby should be tested for hemophilia at birth through cord blood testing, if possible. Cord blood testing instructions and kits are available through the IHTC. Circumcision should be delayed until the infant’s cord blood test results are known.
What Can IHTC Do for You?
- As Indiana’s only federally recognized HTC, the IHTC is committed to working with other healthcare providers throughout the state to serve Indiana’s bleeding disorders population. We are available to answer any questions you or your healthcare provider might have about hemophilia in general and to consult about cases of suspected hemophilia or other bleeding disorders.
- The IHTC will provide detailed surgery plans and postoperative management for any patient who needs a surgical procedure. We gladly take referrals to our center and, based on the benefits of receiving care at an HTC,14 we encourage providers to involve the IHTC in the overall care for persons with hemophilia and their families.
- 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, the IHTC staff also includes a career counselor, a risk reduction specialist, a registered dietitian, genetic counselor, dental hygienist, and clinical research professionals.
- IHTC’s Public Health Service 340B Pharmacy Program allows the IHTC to dispense clotting factor at reduced prices for eligible patients. The IHTC Pharmacy Program benefits payors and patients by reducing the cost of clotting factor, helping patients manage clotting factor needs, and informing patients about patient assistance programs that provide patients with clotting factor during a lapse in insurance coverage. IHTC pharmacy nurses are also ideally situated to coordinate care among patients’ hematologists, pharmacists, and other healthcare providers. See the IHTC Pharmacy Brochure for more information about the services provided by the IHTC Pharmacy Program.
- Genetic counseling is available through the IHTC for individuals and families with blood disorders.
- Our social workers can help individuals with bleeding disorders and their families handle insurance issues.
- Dental care: IHTC’s dental hygienists will work with you and your dentist to make sure required precautions are taken in preparing for dental procedures and for long-term dental care. Visit IHTC’s webpage on dental care to learn more about the special considerations for dental care in persons with bleeding disorders.
- Outreach comprehensive clinic: As Indiana’s only federally recognized HTC, the IHTC is dedicated to serving patients throughout the state. In addition to seeing patients at our clinic, centrally located in Indianapolis, IHTC’s multidisciplinary medical team travels to several Indiana communities each year to conduct comprehensive clinics for patients living in these areas. To find the dates and locations of our outreach clinics, click here.
- The IHTC partners with Hemophilia of Indiana Inc. (HII) to host Camp Brave Eagle, Indiana’s summer camp for children with bleeding disorders. The week-long camp is open to all Indiana children with bleeding disorders, as well as their siblings, ages 7–15 years. For more information on this camp, please click here (Camp Brave Eagle website). For photos of Camp Brave Eagle, see IHTC’s Summer 2014 newsletter in our Reading Room.
- The Doug Thompson Teen Leadership Program, a program of the IHTC and HII, provides teen members of the bleeding disorder community an opportunity to develop and refine life and leadership skills while participating in an adventure camp experience. Teen camp teaches young men how to mentally and physically prepare for nearly anything, while affirming the choice to not participate in activities that may put them at risk mentally or physically. For photos of the Thompson Outpost Teen Camp, see IHTC’s Summer 2014 newsletter in our Reading Room.
- Watch our IHTC News section on this website for further information on registration dates for Camp Brave Eagle and the Thompson Outpost Teen Camp!
- Do you have additional questions about hemophilia? Please see IHTC’s Hemophilia FAQs.
- National Hemophilia Foundation
- World Federation of Hemophilia
- Centers for Disease Control and Prevention (CDC)
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