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 C (Factor XI Deficiency or Rosenthal Syndrome)
What Is Hemophilia C?
While factor VIII and factor IX deficiencies are the best known and most common types of hemophilia, other clotting factor deficiencies also exist. Low levels of factor XI (FXI), another blood protein required for clot formation, cause hemophilia C. This condition is also known as plasma thromboplastin antecedent (PTA) deficiency or Rosenthal syndrome.1-3 Although also associated with bleeding, hemophilia C differs from hemophilia A and B in several ways.
Unlike with hemophilia A and B, the frequency of bleeding with hemophilia C is not determined by the patient’s factor level.1 An unpredictable or inconsistent bleeding pattern occurs in people with this disorder. The inability to predict bleeding complicates treatment. Individuals with hemophilia C do not commonly bleed spontaneously, that is, without known injury. Bleeding tends to occur after surgery or injury, especially in tissues such as the mucosal lining of the mouth, nose, and the urinary tract.1-4
Procedures with an increased risk of bleeding include the following:2
- dental extractions
- surgery in the urinary and genital tracts
- nasal surgery
Unlike individuals with hemophilia A and hemophilia B, patients with hemophilia C do not commonly experience joint bleeds. They may, however, experience the following: bruising, nosebleeds, or blood in the urine; and for women, menorrhagia and prolonged bleeding after childbirth.1-4 Injury may cause bleeding in muscles, joints and other areas.
Causes of Hemophilia C
Throughout the world, persons of Ashkenazi (European) Jewish descent and Iraqi Jews are most commonly affected by hemophilia C.1-4 However, hemophilia C may be diagnosed in many other ethnic groups.4 In the United States, the estimated prevalence of severe hemophilia C is 1 case per 100,000 persons. In Israel, hemophilia C has been estimated to be approximately 8% among Ashkenazi Jews, making it one of the most common genetic disorders.1-4 According to a national database in the United Kingdom, 1696 patients with hemophilia C, including many non-Jewish individuals, were registered in a population of approximately 60 million.5
Hemophilia C is primarily an inherited disorder, but unlike in hemophilia A and B, the gene that causes FXI deficiency is not located on a sex chromosome. The condition, therefore, affects both genders equally. In hemophilia C, parents generally do not experience symptoms, but because of the prevalence of the gene in some populations, an affected parent may marry an individual who carries the disorder and have affected children as well.
Diagnosis of Hemophilia C
Obtaining a detailed personal and family bleeding history of a patient is very important in the diagnosis of hemophilia C. Although this condition is found in all racial and ethnic groups, it is helpful to establish the patient’s background, as this may give an indication of the likely disorder.4
Various screening coagulation tests are utilized to diagnose hemophilia C, the most common being the activated partial thromboplastin time (APTT) and a FXI activity assay.2
Treatment of Hemophilia C
Persons with severe hemophilia C do not require treatment or prophylactic (preventive) therapy for daily activities. However, replacement therapy is required for dental extractions and surgery, and treatment options depend on the type of procedure.
Fresh frozen plasma, the most widely available treatment for this disorder in the United States, is normally used with good results. However, since FXI is not concentrated in fresh frozen plasma, a large volume of this product may be required to raise the FXI activity to a hemostatic level. There are no FXI concentrates licensed in the United States. Two such products are available in Europe, but their use in patients has been limited because there were reports of blood clotting complications after the use of both available concentrates. The patients generally were elderly with pre-existing risk factors for clotting disease.4
Patients with severe FXI deficiency may develop an inhibitor as seen in hemophilia A or B. The development of an inhibitor complicates treatment options. Approximately one-third of patients with severe (<1%) FXI deficiency who use plasma product replacement therapy may develop an inhibitor. There are a few case reports describing the successful use of recombinant FVIIa in these patients; however, recombinant FVIIa should be used with caution because thrombotic complications have been reported.4
Antifibrinolytic agents such as aminocaproic acid (Amicar®) or tranexamic acid may be useful for treating bleeding in mucous membranes in individuals with hemophilia C.2
Complications of Hemophilia C
The complications of hemophilia C are those primarily associated with the use of fresh frozen plasma. While today’s blood products are much safer than those of the past, transmission of hepatitis A, hepatitis C, and newly discovered blood-borne diseases remains a risk for people treated with plasma-derived products, especially when these products are not virally inactivated. Immunization against hepatitis A and B is recommended for all individuals with hemophilia. No vaccination currently exists for hepatitis C.
Living with Hemophilia C
Although persons with hemophilia C often experience milder symptoms than those with hemophilia A or B, this disorder should not be overlooked. People living with hemophilia C require effective treatment to achieve optimal outcomes after surgery or injury. For this reason, it is critical that patients inform their physicians of their diagnosis before any planned procedure.
Table 1 summarizes the key differences between hemophilia C and the relatively more common hemophilia A and B.
|Table 1. Key Differences Between Hemophilia C and Hemophilia A and B|
|Key Characteristic||Difference Between Hemophilia C and Hemophilia A & B|
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 detailed 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,6 we encourage providers to involve the IHTC in the care of individuals with bleeding disorders 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.
- 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.
- Mathew P, Bolton-Maggs P. Hemophilia C. Accessed March 23, 2010
- National Hemophilia Foundation. Factor XI deficiency. Accessed March 23, 2010
- Asakai R, Chung DW, Ratnoff OD, et al. Factor XI (plasma thromboplastin antecedent) deficiency in Ashkenazi Jews is a bleeding disorder that can result from three types of point mutations. Proc Natl Acad Sci U S A. 1989;86:7667-7671.
- Gomez K, Bolton-Maggs P. Factor XI deficiency. Haemophilia. 2008;14(6):1183-1189.
- Bolton-Maggs PH, Peretz H, Butler R, et al. A common ancestral mutation (C128X) occurring in 11 non-Jewish families from the UK with factor XI deficiency. J Thromb Haemost. 2004;2:918-924.
- Soucie J, Nuss R, Evatt B, et al. Mortality among males with hemophilia: relations with source of medical care. Blood 2000;96:437-42.