Delivering Integrated Care Management
The IHTC pharmacy and healthcare professionals interact on a daily basis at our center to maximize coordination and quality of care. Our pharmacists and physicians are on call and available 24 hours a day, seven days a week.
The IHTC pharmacy and healthcare professionals effectively coordinate ongoing care by proactively communicating with our patients to manage clotting factor needs, therapy compliance, and bleeding episodes.
Hemophilia A and B
- What is Hemophilia?
- Causes of Hemophilia
- Signs & Symptoms of Hemophilia
- Emergency Care
- Diagnosis of Hemophilia
- Treatment of Hemophilia
- Treatment Adherence in Hemophilia Care
- Hemophilia Treatment Centers (HTCs) and Comprehensive Care
- IHTC’s Disease Management Program: Optimizing Patient Care While Minimizing Costs
- Special Considerations
- What Can IHTC Do for You?
What is Hemophilia?
Normal blood clotting is a complex process requiring as many as 20 blood proteins, or clotting factors. The deficiency or absence of one of these factors may disrupt the clotting process (see Figure 1).Hemophilia is a rare bleeding disorder characterized by a deficiency or absence of clotting factor VIII (FVIII; hemophilia A) or clotting factor IX (FIX; hemophilia B). Individuals with hemophilia are unable to form blood clots when needed to stop bleeding and therefore bleed longer than people without hemophilia, not faster. Individuals 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 a hallmark of hemophilia. Minor cuts, scrapes, and abrasions are generally not of critical concern for those with hemophilia; however, 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). Deficiency of FXI is called hemophilia C. All of these types of hemophilia meet the NIH definition of a rare disease, namely, one that affects fewer than 200,000 individuals in the United States.1 Both hemophilia A and B affect all races and ethnic groups equally. 2,3 Persons of Ashkenazi (European) Jewish descent and Iraqi Jews are most commonly affected by hemophilia C, although hemophilia C may also be diagnosed in other ethnic groups.
Hemophilia A2: The most common type of hemophilia, FVIII deficiency, occurs in about one in 5,000 male births and affects approximately 25,000 individuals in the United States.
Hemophilia B3: The second most common type of hemophilia, FIX deficiency, is less common than FVIII deficiency. Hemophilia B occurs in about one in 25,000 male births and affects approximately 3,300 individuals 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 this section will focus on hemophilia A and B.
Severity of Hemophilia
Hemophilia is classified as mild, moderate, or severe depending on the amount of the clotting factor present in a person’s blood.2,3 The normal range of FVIII and FIX is between 50% and 150%. Hemophilia severity is classified as shown in Table 1:
|Severity||Blood clotting factor level|
- In mild hemophilia (6% to 49% factor activity), bleeding problems typically occur only after injury, trauma, or surgery; the condition may have very few symptoms otherwise. Approximately 25% of the hemophilia population has mild deficiency.
- In moderate hemophilia (1% to 5% factor activity), bleeding episodes tend to occur after minor injuries, though in some cases spontaneous bleeding episodes (i.e., without obvious cause) may occur. Approximately 15% of the hemophilia population has moderate deficiency.
- In addition to bleeding after injury, trauma, or surgery, severe hemophilia (<1% factor activity) is characterized by spontaneous bleeding into joints and muscles. Recurrent joint bleeding, or hemarthrosis, results in hemophilic arthropathy that may lead to physical disability at a young age. Approximately 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 not apparent. In such cases, the condition is caused by a spontaneous gene mutation at the time of fertilization. 2,3
Hemophilia is a sex-linked condition because the genes for FVIII and FIX are located on the X chromosome, one of the chromosomes that determine a person’s gender. The clinical manifestations of this disease, therefore, are linked to the sex of the affected individual. In brief, a person’s gender is determined by the pairing of two sex chromosomes (X and Y) inherited from the parents. Males (XY) are hemizygous for the X chromosome, receiving an X chromosome from their mothers and a Y chromosome from their fathers. Females (XX) are heterozygous for the affected X chromosome because they inherit X chromosomes from both parents.
Males who inherit the altered gene will express the symptoms of hemophilia (ie, they are symptomatic) as their clotting protein levels are less than 50%. Females who inherit the altered gene may be protected from the bleeding symptoms because of the presence of the other, unaffected chromosome, which helps to synthesize the clotting protein. Females therefore may not express the clinical symptoms of bleeding (ie, they are asymptomatic). Conventionally these females are called carriers. However, female carriers who have low levels (< 50%) of the clotting protein can experience bleeding. These individuals are known as symptomatic carriers. Depending on the levels of clotting protein in these carrier females, the spectrum of clinical symptoms can range from mild to severe hemophilia. For these reasons, it is important to determine each carrier’s factor level to ascertain their risk of bleeding and need for treatment.
Inheritance of Hemophilia
Because hemophilia is a sex-linked recessive disorder and the affected gene on the X chromosome is passed on to the next generation, it is critical to understand the inheritance of hemophilia for family counseling.
Risk of inheriting hemophilia from a father with hemophilia and an unaffected mother
Men who have hemophilia will pass their affected X chromosome to ALL of their daughters; therefore, all daughters of an affected father will be carriers of hemophilia regardless of their factor levels. These daughters are conventionally known as obligate carriers. Sons of men with hemophilia will receive a Y chromosome from their fathers, rather than an X, and therefore will not be affected by hemophilia or carry the gene. Thus all the daughters of men with hemophilia will be carriers of the gene while the sons will never have hemophilia (see 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.
Risk of inheriting hemophilia from a father without hemophilia and a mother who is a hemophilia carrier
A woman who is a carrier of hemophilia can pass on an affected X chromosome to her son or daughter. Thus there is a 50% chance that each son or daughter will inherit the affected X chromosome from their mother. If a male child inherits his mother’s affected X chromosome, he will have hemophilia, but if he inherits the normal X chromosome he will not have hemophilia. If a female child inherits her mother’s affected X chromosome, she will be a carrier. Thus, there is a 50% chance that the daughter of a carrier mother will also be a carrier of hemophilia. There is a 50% chance that the son of a carrier mother will have hemophilia (see Figure 3).
Figure 3: 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.
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.
Males with hemophilia cannot pass the condition onto their sons, but all daughters will be carriers of the trait (Figure 2).
Women with Hemophilia
As an X-linked recessive trait, hemophilia occurs almost exclusively in males. There are circumstances, however, when females experience bleeding symptoms.
- Symptomatic carriers: In some cases, female carriers of hemophilia can have low (< 50%) levels of 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 In general, musculoskeletal bleeding is the hallmark of hemophilia. The extent of these symptoms depends on the type of hemophilia and the severity of the underlying deficiency.
Common symptoms of hemophilia include the following:
- Joint bleeding or hemarthrosis
- Soft tissue bleeding or development of hematoma after minor trauma
- Bleeding after circumcision
- Easy or excessive bruising
- Prolonged bleeding after oral injury
- Bleeding associated with surgery or invasive procedures
Subsequent sections will elaborate on commonly encountered symptoms of hemophilia.
Bleeding into the joints
Spontaneous or trauma-induced bleeding into the joints (hemarthrosis) is the primary cause of chronic pain and disability among individuals with severe hemophilia.7 Chronic bleeding into the joints disrupts the joint lining (synovium) and causes joint damage, resulting in the painful arthritic condition known as hemophilic arthropathy. Bleeding most commonly occurs in the knees, elbows, ankles, and hips; but can occur in any joint. While joint bleeding can occur in all severities of hemophilia, spontaneous joint bleeding tends 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 bleeding are not always immediately apparent. The initial symptom is often tingling or tightness in the joint with no real pain or visible signs of bleeding. As bleeding continues, the joint becomes swollen, warm to touch, and painful to move. Swelling increases as bleeding continues and movement can be temporarily lost. Pain can be severe. Joint bleeding must be treated quickly and aggressively to prevent permanent joint damage. Untreated joint bleeding can be debilitating, as chronic pain, swelling, and permanent joint damage lead to limited mobility and decreased quality of life.
Bleeding in soft tissue
Soft tissue (muscular) bleeding, such as in the iliopsoas muscle, can cause severe anemia and hemodynamic instability. Bleeding within compartments such as the forearm or lower extremity can cause compartment syndrome. These patients present with significant neurovascular compromise and symptoms of pain, tingling, numbness or paresthesis. Compartment syndrome requires immediate specific treatment with hemostatic agents and consideration of decompression of neurovascular structures.
Bleeding in the central nervous system
Bleeding in the central nervous system causes significant morbidity and mortality in patients with hemophilia.6 These patients can present with the following symptoms:
- Head – headache, neck pain, sleepiness, sensitivity to light, nausea, vomiting, loss of consciousness or seizures.
- Spinal cord – weakness, tingling, or pain in the arms or legs; difficulty with urination or bowel movements, back pain, loss of movement.
Bleeding in the gastrointestinal tract
Individuals with hemophilia may experience gastrointestinal bleeding with bloody emesis or lower intestinal bleeding such as hematochezia. These bleeding events could be due to bleeding ulcers or bleeding from a diverticulum. Depending on the site of bleeding, the manifestations of gastrointestinal bleeding may range from fresh or brown-colored emesis to black and tarry stools.
Life-threatening bleeding events in patients with hemophilia
Rarely patients can have bleeding within vital internal organs or structures. These are often life-threatening bleeding events.
- Bleeding into the central nervous system
- Bleeding within vital structures such as head, neck, or intrathoracic region
- Bleeding within internal organs such as liver and spleen
- Bleeding in a large muscle group, such as iliopsoas
- Gastrointestinal bleeding
Table 2 summarizes the relationship between symptoms and the type and severity of the hemophilia.
|Topic||Severity of Hemophilia|
|FVIII or FIX activity||< 1%||1% – 5%||6% – 49%|
|Cause of bleeding||Spontaneous||Minor trauma, not commonly spontaneous||Major trauma, surgery|
|Frequency of bleeding||2 – 4/month||4 – 6/year||Uncommon|
|Pattern of bleeding||Joint, soft tissue, bleeding after circumcision, neonatal intracranial hemorrhage, bleeding with surgical procedures||Joint, soft tissue +/- bleeding after circumcision, +/- neonatal intracranial hemorrhage, bleeding with surgical procedures||Joint, soft tissue, +/- bleeding after circumcision, bleeding with surgical procedures|
If your patient with a bleeding disorder needs to visit the emergency department (ED), encourage them to contact the IHTC so that the center can help them get the best possible emergency and follow-up care. Visit our webpage on Emergency Care to learn about what patients and their families should do, what they need to take to the ED, and what information they need to provide to the ED staff. Inform your patients about the IHTC’s useful Emergency Care Tips.
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 evaluation
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. The activated partial thromboplastin time (aPTT) assay evaluates the intrinsic pathway of coagulation and is quite often prolonged in patients with hemophilia. If the aPTT is prolonged, a mixing study is performed to evaluate the correction of a patient’s aPTT with a pooled plasma from healthy donors.
In patients with coagulation factor deficiencies, the aPTT is corrected in a 1:1 mixing study. If a factor deficiency is suspected, then specific factor assays such as FVIII and FIX levels are performed to diagnose the type and severity of the deficiency. These assays are best performed in specialized coagulation laboratories.
It is important to underscore that in patients with mild hemophilia, the aPTT assay may be normal. If the aPTT does not correct, then conditions such as inhibitors against coagulation factors are considered.
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 mutation causing hemophilia. Genetic tests are particularly helpful in diagnosing the carriers in the family as they are often asymptomatic and may have normal levels of the clotting factor proteins.
Diagnosis of hemophilia in newborns
In newborns who experience bleeding from heel sticks, hematoma or bleeding after an intramuscular injection, bleeding with circumcision, cephalic hematomas, subgaleal bleeding, or bruising, diagnostic tests are warranted. 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 adult 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. It is recommended that clinicians consult with HTC staff before ordering tests and for assistance with interpretation of test 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 and tissue factor. 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 ultrasonography. 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 of the condition has advanced remarkably in the past 30 years such that children with hemophilia who receive comprehensive treatment can now look forward to a near-normal life expectancy.8 Hemophilia is managed effectively 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 can be made using human plasma or through recombinant technology.
Clotting Factor Concentrates
- Plasma-derived products: plasma-derived products are made from human blood products such as donated plasma
- Recombinant products: recombinant factor products are synthesized in the laboratory using recombinant technology. These products do not use human blood as a starting substrate. Recombinant products offer a potentially safer alternative to plasma-derived products because they avoid possible blood-borne transmission of infectious diseases to the hemophilic population. In the United States, treatment with recombinant products, when available, is the standard of care.
Clotting factor concentrates are administered by placing a needle in the patient’s vein (venipuncture) or through a surgically implanted device called a Port-a-Cath. This replacement (or infusion) therapy stops or prevents bleeding by increasing the patient’s factor level for a certain time period. Patients and parents of patients who require frequent infusions often learn to infuse at home, making treatment more convenient and accessible for the patient and the family.
Factor replacement products are typically provided to patients through hemophilia treatment center (HTC) pharmacy programs or homecare companies. As Indiana’s only federally recognized comprehensive treatment center, the IHTC operates a Public Health Service 340B Pharmacy Program. The 340B program allows the IHTC to dispense clotting factor at reduced prices. Visit the IHTC Pharmacy Program to learn more about how IHTC’s pharmacy program works with payors and patients to reduce costs and optimize the care provided to individuals with bleeding disorders.
The amount of factor and the frequency of administration depend on several variables including the severity and site of the bleeding, and the size of the patient. There are two main categories of treatment regimens.
Hemophilia Treatment Regimens
Prophylactic Infusion Therapy (Prophylaxis)
The Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation and the World Health Organization (WHO) recommend prophylactic treatment as optimal therapy for persons with severe hemophilia A or B.9 10 Prophylactic therapy involves regular administration of clotting factor concentrates, often 2 to 3 times per week, to increase the factor level to a moderate range (> 1%) to prevent spontaneous bleeding or bleeding after minor injury. The dose and frequency of prophylactic infusion therapy varies according to the severity of the bleeding phenotype and the patient’s response to therapy. Prophylactic infusion programs use a considerable amount of factor concentrate to minimize the number of bleeding episodes.
Episodic Infusion Therapy (“On-Demand”)
Episodic treatment of bleeding disorders is defined as utilization of clotting factor concentrates in response to an acute bleeding episode to stop bleeding after it has started. In general, individuals with mild and moderate hemophilia, who tend to bleed less frequently, use episodic infusion of factor concentrates.
Click here for MASAC’s recently updated recommendations on the treatment options for hemophilia and other bleeding disorders. Click here to download the IHTC’s fluid restriction guidelines and other information on DDAVP/Stimate use.
Treatment Adherence in Hemophilia Care
The effectiveness of hemophilia treatment depends on two important variables: the physician recommending an appropriate treatment plan for the patient’s condition, and the patient following the recommendations that are given. Treatment adherence is the extent to which a patient’s behavior coincides with medical or health advice. Because hemophilia often requires significant patient self-care at home, treatment adherence in hemophilia requires active involvement of the patient in working with physicians to plan and manage a treatment regimen.
Poor adherence to a hemophilia treatment plan may reduce treatment effectiveness and contribute to long-term disability and decreased quality of life among patients. Nonadherence to on-demand/episodic therapy may result in bleeding episodes of longer duration, recurrent bleeds in the same location, severe joint damage and subsequent disability. Nonadherence to prophylactic therapy may cause suboptimal prevention of bleeding events and lead to the poor outcomes that prophylaxis is designed to prevent, such as joint damage and disability. Because clotting factor is an expensive medication, it is especially important for patients to adhere to treatment recommendations to prevent complications and reduce waste of a valuable medical resource.
While most hemophilia providers agree that treatment adherence is an important issue in hemophilia-related health outcomes, historically there has not been an effective way to measure treatment adherence in individuals with hemophilia. Different studies have used infusion logs, clotting factor dispensations, joint health, and patient interviews to evaluate adherence. However, none of these studies resulted in a standardized method to measure adherence to hemophilia treatment. In response to the need for a standardized measure, the IHTC developed and validated two scales to measure treatment adherence – the Validated Hemophilia Regimen Treatment Adherence Scales (VERITAS) for episodic treatment (VERITAS-PRN) and for prophylactic treatment (VERITAS-Pro).
VERITAS: IHTC’s Validated Treatment Adherence Scales
Each VERITAS scale includes 24 questions divided into six 4-question subscales. The subscales are designed to measure different aspects of treatment adherence, including the dosage and timing of infusions, the patient’s tendency to forget or skip infusion, and the frequency of communication between the patient and the HTC. Using the individual subscale scores as well as the total score allows care providers to evaluate multiple dimensions of adherence and to identify areas that should be addressed to improve adherence and optimize long-term health outcomes for the patient.
The validation process involved developing these questionnaires and testing them in patient groups to demonstrate that the scales measure what they purport to measure, i.e., that they measure actual treatment adherence and not another aspect of hemophilia treatment. We demonstrated that the scales reliably measure treatment adherence and represent a valuable tool for use in patient care. The scales take less than ten minutes to complete and are a simple and highly informative addition to a patient’s clinic visit and care.
Both scales were published in Haemophilia in early 201011,12 and have been well received in the hemophilia community. To date, the IHTC team has 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 currently undergoing translation into Spanish, Italian, and French, and has been introduced to multiple clinic settings and added to several pharmaceutical study protocols. It is our hope that the VERITAS scales will improve our understanding of the link between treatment adherence and health outcomes, and thus significantly influence our ability to help patients achieve the best long-term outcomes possible.
Please use the following links to read the VERITAS study abstracts in the journal Haemophilia.
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 firstname.lastname@example.org.
Hemophilia Treatment Centers (HTCs) and Comprehensive Care
The federal Office of Maternal and Child Health at the Centers for Disease Control and Prevention (CDC) support a network of specialized healthcare centers that prevent and reduce complications associated with blood disorders.13 Currently, the network consists of approximately 140 hemophilia treatment centers (HTCs), eight hemostasis and thrombosis centers, and seven thalassemia care centers. The IHTC is Indiana’s only federally recognized HTC.
The purpose of HTCs is to provide optimal and comprehensive care to persons with bleeding disorders, thrombosis, and thrombophilia. The centers use multidisciplinary teams of healthcare specialists and clinical, 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 in HTCs has been shown to significantly decrease 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.
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 specialist, registered dietitian, clinical research professionals, a genetic counselor, and dental hygienist.
IHTC’s Disease Management Program: Optimizing Patient Care While Minimizing Costs
Since October 2004, the IHTC has administered a disease management program (DMP) for persons with bleeding disorders who are insured by Indiana’s high-risk insurance pool, the Indiana Comprehensive Health Insurance Association (ICHIA). Indiana code I.C. 27-8-10-3.5(e) mandates that ICHIA-insured individuals with chronic diseases participate in an ICHIA-approved DMP. Because of IHTC’s specialized focus on bleeding disorders and commitment to excellence in patient care, it was selected as the disease management entity for ICHIA-insured individuals with bleeding disorders.
The purpose of the DMP is to optimize patient care and health outcomes while containing or reducing costs of care. The program brings together expertise, experience, and advanced technology in a patient-focused, research-oriented approach. All elements of the DMP are targeted toward the most accurate, effective, and efficient methods to diagnose and treat bleeding disorders. Through targeted interventions and enhanced quality assurance, this program is expected to result in better patient care and savings in costs of care.
Patients enrolled in the program are required to do the following:
- Attend an annual comprehensive clinic at the IHTC or at an outreach location;
- Have prescriptions for clotting factor concentrate and other bleeding disorder medications signed by an IHTC physician;
- Obtain outpatient clotting factor and related products through one of the ICHIA DMP Public Health Service vendors, such as the IHTC Pharmacy Program;
- Engage in periodic telephone contact with IHTC/DMP nurses and staff regarding ongoing health issues, psychosocial concerns, and educational or occupational needs;
- Complete DMP questionnaires and assessments upon request;
- Use the ATHNadvoy web-based infusion reporting system or other approved infusion reporting system to log infusions.
Program enrollees also have the option to participate in the research component of the DMP, whereby program results may be presented to other HTCs and/or published in academic journals. Patient privacy is always a priority at the IHTC. Any data that are published or presented are carefully de-identified and aggregated so that no individual patients can be linked to the information.
Evaluation of Progress
The following tools are used to evaluate program progress:
- Monthly meetings of the multidisciplinary team to review DMP patients’ health status, progress, and needs;
- Pharmacoeconomic analysis of claims data – i.e., annual insurance claims are reviewed from year to year, with a special focus on costs of care, costs of clotting factor, source of care (e.g., HTC, emergency department), and changes in costs and utilization from one year to the next;
- Annual reporting of specific cost and utilization outcomes:
- Average costs of clotting factor, medical, and hospital care;
- Average number of clotting factor units dispensed, emergency department visits, and inpatient hospital days;
- Regular patient assessments:
- Diagnosis-specific knowledge assessments – to assess a patient’s knowledge of his or her own condition, and to assess changes in knowledge over time;
- Quality of life survey – to assess a patient’s health-related quality of life, and to assess changes in quality of life over time;
- Treatment adherence scale – VERITAS-Pro or VERITAS-PRN for patients who use a home infusion regimen.
The DMP is currently in its sixth year of administration. Five years after implementation, all costs, as well as emergency department visits, have remained below baseline levels. Inpatient hospital days also have remained below baseline, although there have been a few spikes in costs for medically necessary surgeries. Program patients have benefited from the focus on proactive, preventive care and personalized interventions. A major strength of the IHTC DMP is that it is administered by healthcare providers rather than a third-party disease management entity. This ensures that program staff has direct access to the multidisciplinary medical team, hemophilia physicians, and clotting factor pharmacy. This model strongly supports the implementation of provider-administered DMPs in managing chronic disease and addressing the rising healthcare costs in the United States.
The IHTC team published the initial results of its DMP in Haemophilia, a leading peer-reviewed, academic journal. To access the abstract of the published article, click here
Availability and Cost of Hemophilia Treatment
Treatment with clotting factor concentrate is expensive, accounting for up to 90% of the costs of care in hemophilia.15,16 The average annual cost of care has been estimated to range from about $19,000 in individuals with mild or moderate hemophilia to $300,000 in individuals with severe hemophilia.16,17 In the presence of complications and/or comorbidities, the cost of care easily exceeds this range.
The high cost of care can lead to difficulties in accessing health insurance and paying for care. HTC social workers are knowledgeable about insurance options and are available to help ensure that patients have continued access to optimal care. IHTC’s Pharmacy Program assists patients with enrollment in patient assistance programs so that patients have access to clotting factor during a lapse 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 with the procedure and with long-term dental health. Clinicians are encouraged to visit IHTC’s webpage on dental care to learn more about the special considerations for dental care in patients with bleeding disorders. IHTC’s dental hygienists will work with you and your patients with bleeding disorders to make sure the necessary precautions are taken in preparing for dental procedures and for long-term dental care.
One of the most serious complications in the treatment of hemophilia is the development of an inhibitor, which is an antibody against the clotting factor concentrate used in replacement therapy. Antibody formation is the body’s immune response toward foreign proteins. Because individuals with hemophilia are deficient or lacking in a specific clotting factor protein, replacing the clotting factor can result in an immune response in some individuals, as their bodies identify the clotting factor as “non-self” and thus destroy the infused clotting factor. Up to 30% of individuals with severe or moderate FVIII deficiency and 1% to 6% of individuals with severe FIX deficiency develop inhibitors.18
The presence of inhibitors reduces or eliminates the efficacy of clotting factor replacement therapy. In cases of low-titer inhibitors, higher-than-usual doses of clotting factor concentrate may be effective treatment. In individuals with high-titer inhibitors, use of clotting factor replacement is not possible. In these individuals, bypassing agents such as prothrombin complex concentrate (PCC), activated PCC (aPCC), and recombinant activated FVII (rFVIIa) are used for hemostatic control.
Immune Tolerance Induction
Immune tolerance induction (ITI) is an intensive treatment that aims to reduce or eliminate inhibitors against clotting factor. This treatment entails regular use of doses of clotting factor concentrates and/or immunomodulating agents to tolerize the immune system to the clotting factor. ITI regimens require commitment from the patient and family as some regimens utilize infusion as often as twice per day.19
Because they reduce the effectiveness of clotting factor replacement therapy, inhibitors further complicate hemophilia treatment, thereby increasing the cost of care due to the high cost of bypassing agents and ITI regimens. It has been estimated that in individuals with FVIII inhibitors with unfavorable prognosis, there is an 8-fold increase in FVIII consumption and cost of care.20
The IHTC provides immune tolerance clinics for individuals with inhibitors. To read more about the services provided through clinic, click here.
Thanks to significant improvements in treatment and prevention of bleeding episodes, the life expectancy of individuals with hemophilia is now approaching that of the general population.8 As a result, individuals with hemophilia are now presenting with comorbidities associated not only with hemophilia, but also with aging, such as cardiovascular disease. The older generation of individuals with hemophilia presents new challenges to providers at HTCs and other healthcare professionals and requires a holistic, coordinated approach to their healthcare.
In the aging population, comorbidities related to hemophilia may include:
- Hemophilic arthropathy, including chronic pain and reduced bone mineral density. Patients may also need physical therapy, rehabilitation, and/or orthopedic surgery. These individuals may be at increased risk for injuries associated with balance dysfunctions and associated increased risk of falls.
- Chronic hepatitis C, hepatocellular carcinoma, and end-stage liver disease.
- HIV and complications related to treatment with HAART (highly activated antiretroviral therapy).
- Inhibitor development, especially among elderly patients with mild hemophilia who have not been exposed to clotting factor replacement therapy.
- Renal abnormalities
In older individuals, comorbidities not related to hemophilia may include:
- Diabetes mellitus
- Cardiovascular disease
- Dental problems requiring surgical extraction
- Erectile difficulty and sexual dysfunction
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 cardiac 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. Additionally, IHTC’s professional development program, Partners in Bleeding Disorders Education, provides a free interactive module titled Cardiovascular Disease in an Adult with Hemophilia.
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. The IHTC’s newsletter explains which tests should be ordered.
Because comorbidity in aging individuals with hemophilia may require complex treatments, coordination of care among various healthcare specialists is essential. To address issues such as cardiovascular disease in patients with hemophilia, the IHTC conducts regular screening for the diagnosis and evaluation of cardiovascular disease in patients with hemophilia. This screening has been incorporated into the annual comprehensive clinic visit.
Blood Product Safety
Thanks to improved blood screening, testing, viral inactivation and removal methods, and the development of recombinant factor concentrates, today’s factor replacement products are much safer than those of the past. Transmission of hepatitis A, B, and C, and other blood-borne diseases is now only a small risk for people treated with human plasma-derived products. While no vaccination currently exists for hepatitis C, immunization against hepatitis A and B is recommended for all hemophilia patients, regardless of their type of factor product.
IHTC’s risk reduction specialist counsels individuals with bleeding disorders about steps they need to take to reduce or prevent complications related to their bleeding disorder or its treatment.
Individuals with hemophilia can take measures to remain in good health and to prevent poor outcomes associated 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 bleeding
- Maintain good oral hygiene (to prevent extensive dental procedures)
- Exercise regularly and maintain a healthy body weight
- Identify and treat bleeding events promptly, as directed by the hematologist
Carrier Testing for Women
Carrier testing is available to determine whether a woman with a family history of hemophilia is a carrier. Genetic testing is the most accurate method of carrier testing. It involves obtaining a blood sample to look for the specific gene alteration in the FVIII or FIX gene that caused hemophilia in a family. Carrier testing using factor levels is not 100% accurate. Some women carriers can have normal factor levels and may be classified as “non-carriers” if tested with factor levels. Inaccurate information can result in medical errors.
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 allows for prenatal diagnosis if desired, and may indicate precautions to be taken during the pregnancy, labor, and delivery.
In women who are or may be carriers of hemophilia, difficult delivery (notably, prolonged second stage of labor, use of forceps, or vacuum extraction) 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 test results are known.
The National Hemophilia Foundation’s MASAC recently updated its guidelines for perinatal management of women with bleeding disorders and carriers of hemophilia A and B. These updated guidelines may be viewed here.
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 might have about hemophilia in general and to consult about cases of suspected hemophilia or other bleeding disorders.
- The IHTC will provide surgery plans and postoperative management for any patient undergoing a surgical procedure. We gladly accept referrals to our center and, based on the documented benefits of receiving care at an HTC,14 we encourage providers to involve the IHTC in the care of individuals 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(e.g., hematologists, clinical nurses, social workers, physiotherapists), the IHTC staff also includes a career counselor, risk reduction specialist, registered dietitian, clinical research professionals, genetic counselor and dental hygienist.
- IHTC’s Public Health Service 340B Pharmacy Program allows the IHTC to dispense clotting factor at significantly reduced prices for eligible patients, saving millions of dollars. The IHTC Pharmacy Program benefits payors and patients by reducing the cost of clotting factor, coordinating care management, proactively communicating with patients and their families to manage clotting factor needs, and assisting patient enrollment in patient assistance programs so that patients can get their clotting factor during a lapse in insurance coverage.
- Genetic counseling is available through the IHTC for families with hemophilia.
- Our social workers can help individuals with bleeding disorders and their families navigate insurance issues.
- Dental care: IHTC’s dental hygienists will work with individuals with bleeding disorders and their dentists 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.
- Partners in Bleeding Disorders Education Program: The Partners Program is the longest-running curriculum-based national educational program for HTC professionals. The program offers in-person and online comprehensive education for HTC staff and includes directed educational components for HTC disciplines such as physical therapy and social work. To learn more about these professional development activities, visit http://www.partnersprn.org.
- 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. For the dates and locations of IHTC’s 2010 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 summer camps for your patients, please refer them to the Camps page on this website or the Camp Brave Eagle website. See photos of these camps in the Summer 2014 issue of IHTC’s newsletter, the Clotting Times.
- 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.
- To answer additional questions that your patients may have about hemophilia care, see IHTC’s Hemophilia FAQs.
- National Hemophilia Foundation
- World Federation of Hemophilia
- Centers for Disease Control and Prevention (CDC)
- National Institutes of Health. Office of Rare Diseases Research. Rare Diseases and Related Terms. (Accessed March 23, 2010)
- Hemophilia A (Factor VIII Deficiency). National Hemophilia Foundation, 2006. (Accessed December 18, 2009)
- National Hemophilia Foundation. Hemophilia B (Factor IX), 2006. Available at: http://www.hemophilia.org/NHFWeb/MainPgs/MainNHF.aspx?menuid=181&contentid=46&rptname=bleeding. (Accessed December 18, 2009)
- The Internet Encyclopedia of Science. Hemophilia. (Accessed December 29, 2009)
- National Heart, Lung, and Blood Institute. What Are the Signs and Symptoms of Hemophilia? Available at: http://www.nhlbi.nih.gov/health/dci/Diseases/hemophilia/hemophilia_signs.html (Accessed December 30, 2009)
- Butler R, Crudder S, Riske B, et al. Basic Concepts of Hemophilia. Atlanta, GA: Centers for Disease Control and Prevention (CDC).
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- Medical and Scientific Advisory Council (MASAC) recommendation #179: MASAC recommendation concerning prophylaxis (regular administration of clotting factor concentrate to prevent bleeding). 2007. (Accessed January 7, 2010)
- World Health Organization. Delivery of Treatment for Haemophilia: Report of a Joint WHO/WFH/ISTH Meeting London, United Kingdom, 11- 13 February 2002. In. London, United Kingdom: WHO; 2002.
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