Hemophilia C, also known as factor XI deficiency, is a type of bleeding disorder. It occurs due to a deficiency in factor XI, which is a protein that plays an important role in the formation of blood clots.
Hemophilia is a group of bleeding disorders. The term hemophilia derives from Greek and refers to the characteristic symptom of excessive bleeding.
There are many types of hemophilia, but they all occur due to problems with forming a blood clot.
Also known as plasma thromboplastin antecedent deficiency, or Rosenthal syndrome, hemophilia C occurs due to problems with blood clotting factor XI. Without this specific protein in the blood, injured blood vessels cannot form a blood clot and heal in the usual way.
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This gene alteration results in a reduction in the amount of factor XI in the bloodstream or the production of factor XI that does not function correctly. As such, a deficiency of functional factor XI slows blood clotting, which can cause episodes of excessive bleeding.
During the blood clotting cascade, factor XI plays the important role of helping to generate thrombin. This is a protein in the blood that converts fibrinogen to fibrin. This process traps platelets, which helps to hold a blood clot in place.
Hemophilia A is the most common type of hemophilia. It occurs due to a deficiency of factor VIII due to variations in the F8 gene. Hemophilia B is another common type of hemophilia. It develops due to a variation in the F9 gene, which results in a deficiency of factor IX.
As such, there are many less common factor deficiencies, which include:
- factor I deficiency
- factor II deficiency
- factor V deficiency
- factor VII deficiency
- factor X deficiency
- factor XII deficiency
- factor XIII deficiency
Unlike some other types of hemophilia, factor XI deficiency affects males and females in equal numbers. This is because unlike other genes for hemophilia, which are present on the X chromosome, the F11 gene is present on chromosome 4. It is the second most common bleeding disorder that affects females, after von Willebrand’s disease.
Hemophilia C can impact people of any age and any ethnic group. However, it is more prevalent in certain populations. The incidence of hemophilia C is roughly 1 in 1,000,000 in the general population.
However, it is more prevalent in people with Ashkenazi Jewish ancestry, occurring in about 1 in 450 individuals in that population. It also affects a higher number of people in the Basque population of Southern France.
Typically, hemophilia C is an inherited genetic condition. This means that a person inherits the gene alterations from their parents. Usually, a person will inherit hemophilia C in an autosomal recessive pattern. This means a person will need to inherit the gene variation from both parents for the condition to develop.
While hemophilia C usually follows an autosomal recessive pattern, some people, such as those of Ashkenazi Jewish ancestry, may inherit it through an autosomal dominant pattern (from one parent). This may explain why hemophilia C is more prevalent in this population.
Some people may inherit one copy of the gene variation and not develop the condition. These individuals are known as carriers, as they can pass the alteration on to their children. Although these people do not develop a severe form of hemophilia C, they may still have slightly lower than normal factor XI levels and experience mild symptoms.
Read on to learn more about the inheritance pattern of hemophilia.
While most cases of hemophilia C occur due to inheritance, it is also possible to develop the condition later in life. When this occurs, it is known as acquired hemophilia C.
Generally, this may occur due to problems with the liver, as production of factor XI primarily occurs in the liver. As such, it can result from liver disease or from receiving a liver transplant from an individual with a factor XI deficiency. Additionally, it may also occur from the immune system mistakenly attacking the factor XI protein.
Many people with a factor XI deficiency may not show symptoms. Additionally, unlike other types of hemophilia, symptoms are not necessarily worse with lower levels of factor XI.
Possible symptoms of hemophilia C include:
- frequent nosebleeds or soft tissue bleeds
- excessive bleeding when the umbilical cord is cut after birth
- bleeding after dental procedures, surgery, or trauma
- development of hematomas, or solid swellings of congealed blood, after surgery
- menorrhagia, or heavy menstrual bleeding
- bleeding after childbirth
- delayed bleeding
Unlike other types of hemophilia, a person with hemophilia C is unlikely to experience joint and muscle bleeds or spontaneous periods of bleeding.
In some cases, a person may receive a diagnosis of hemophilia C before birth if there is a family history.
- bleeding time test
- platelet function tests
- prothrombin time (PT) test
- activated partial thromboplastin time (aPTT) test
To confirm a diagnosis, a factor XI assay may be necessary. An assay can measure the activity of certain substances in the blood. As such, a factor XI assay will demonstrate a reduced activity of factor XI.
A potential complication of hemophilia C, and other types of hemophilia, is the development of autoantibodies known as inhibitors.
Autoantibodies refer to proteins that the immune system produces that mistakenly target healthy tissues. In this case, the inhibitors target replacement factor XI, which can impact the effectiveness of treatment. To help manage this, a doctor may recommend additional therapy, such as factor VII therapy.
If a person does not have problematic symptoms of hemophilia C, treatment may not be necessary. In many cases, a person may only require treatment prior to undergoing some types of surgery or similar procedures.
Treatment can involve replacement therapy with factor XI concentrates. This refers to blood products that scientists produce in a laboratory that contain a concentrated form of factor XI. However, factor XI concentrates are not available in the United States.
Instead, in the U.S., people will receive fresh frozen plasma (FFP). This is a blood derivative that comes from blood donors and is rich in clotting factors, such as factor XI. However, as it is not a concentrate, large volumes of FFP are often necessary.
Other treatment options include fibrin glue to help treat skin injuries, tranexamic acid, which can help make blood clots more stable, and aminocaproic acid, which helps to control nosebleeds and bleeding after dental procedures.
Individuals may also need to take additional measures to make their monthly period manageable. This may include using tranexamic acid or using contraceptive methods, such as birth control pills.
It is also advisable that people with severe factor XI deficiency avoid nonsteroidal anti-inflammatory drugs (NSAIDs). This is because these drugs can increase the risk of bleeding. Instead, it is advisable to use other methods of pain relief.
Hemophilia C is a bleeding disorder. It typically occurs due to a deficiency of clotting factor XI, which plays a role in the formation of blood clots.
People may not always experience symptoms. However, a deficiency of clotting factor XI can result in excessive bleeding, particularly after surgery. Treatments, such as factor XI concentrates and fresh frozen plasma, can help with blood clot formation and make symptoms manageable.