What is Hemophilia A?
Hemophilia A, also known as classic hemophilia, is a hereditary bleeding disorder caused by a lack of or defect in clotting factor VIII. In a healthy individual, a complex process called the coagulation cascade involves multiple proteins, or clotting factors, that work in a sequence to form a blood clot and stop bleeding. When there is insufficient functional factor VIII, this chain reaction is interrupted, resulting in prolonged and excessive bleeding.
Causes and Inheritance
Most cases of hemophilia A are inherited and caused by a mutation in the F8 gene, which provides instructions for making factor VIII. The disorder is an X-linked recessive condition, meaning the gene is located on the X chromosome.
- Genetic inheritance: Since males have one X and one Y chromosome, and females have two X chromosomes, the inheritance pattern differs. A male with the mutated F8 gene on his single X chromosome will have hemophilia A. A female with one affected X chromosome is a carrier and can pass the gene to her children. It is very rare for a female to have hemophilia, as it would require both X chromosomes to carry the mutated gene.
- Spontaneous mutations: In about one-third of cases, there is no family history, and the condition is the result of a spontaneous genetic mutation.
- Acquired hemophilia A: In rare instances, individuals can develop acquired hemophilia A later in life. This is an autoimmune disorder where the immune system attacks and destroys the body's own factor VIII.
Symptoms of Hemophilia A
The severity of hemophilia A symptoms depends on the amount of functional factor VIII in the blood. The classification is based on the percentage of normal factor activity:
- Severe hemophilia A: Less than 1% of normal factor VIII activity. Individuals experience frequent, spontaneous bleeding, often into joints and muscles.
- Moderate hemophilia A: Between 1% and 5% of normal factor VIII activity. Bleeding episodes typically occur after an injury, but spontaneous bleeding can also happen.
- Mild hemophilia A: Between 6% and 49% of normal factor VIII activity. Prolonged bleeding usually only occurs after serious injury, trauma, or surgery.
Common symptoms of hemophilia A include:
- Many large or deep bruises
- Joint pain and swelling from internal bleeding, particularly in the knees, elbows, and ankles
- Excessive bleeding from cuts, injuries, or after surgery
- Unexplained nosebleeds
- Blood in the urine or stool
Diagnosis
The diagnostic process for hemophilia A typically involves several tests to confirm the condition and determine its severity.
- Partial Thromboplastin Time (PTT): A blood test that measures the time it takes for blood to clot. A prolonged PTT is a key indicator of a potential clotting factor deficiency.
- Factor VIII Activity Assay: This specific test measures the amount of functional factor VIII in the blood, confirming the diagnosis and severity level.
- Genetic Testing: Molecular genetic testing can identify the specific mutation in the F8 gene, which is useful for confirming a diagnosis and for genetic counseling.
Modern Treatments and Management
Thanks to advancements in treatment, many people with hemophilia A can lead full and productive lives. The primary goal is to replace the missing clotting factor, either as a preventative measure or to treat bleeding episodes.
Common treatment and management strategies include:
- Factor replacement therapy: This involves infusing factor VIII concentrates intravenously to replace the deficient protein. For severe cases, this is often done proactively (prophylaxis) on a regular schedule to prevent bleeding.
- Non-factor replacement therapies: Newer medications, such as emicizumab (Hemlibra), mimic the function of factor VIII and are administered as a subcutaneous injection, offering a less frequent dosing schedule.
- Desmopressin (DDAVP): Used for mild hemophilia A, this medication helps the body release stored factor VIII.
- Gene therapy: A one-time treatment option, such as Roctavian, was approved by the FDA in 2023 for adults with severe hemophilia A. It aims to provide the body with a working copy of the F8 gene.
- Physical therapy: Regular physical therapy is crucial for strengthening muscles and joints that have been affected by internal bleeding.
- Lifestyle modifications: Avoiding contact sports, certain pain medications (like aspirin), and taking precautions to prevent injury are key aspects of managing the condition.
Comparison of Hemophilia A and Hemophilia B
While hemophilia A is the result of a factor VIII deficiency, it is often compared to Hemophilia B, which is a deficiency of factor IX. The table below highlights the key differences.
| Feature | Hemophilia A | Hemophilia B |
|---|---|---|
| Missing Clotting Factor | Factor VIII | Factor IX |
| Alternate Names | Classic Hemophilia | Christmas Disease |
| Gene Location | F8 gene on the X chromosome | F9 gene on the X chromosome |
| Prevalence | Approximately 1 in 5,000 live male births | Less common than Hemophilia A |
| Inheritance Pattern | X-linked recessive | X-linked recessive |
| Treatment | Factor VIII concentrates, emicizumab, gene therapy | Factor IX concentrates, gene therapy |
| Severity | Ranges from mild to severe based on factor levels | Ranges from mild to severe based on factor levels |
Conclusion
To answer the question, Hemophilia A is the disorder that results from a deficiency of factor VIII. This genetic bleeding disorder, while lifelong, is effectively managed with modern treatments and proactive care. The outlook for individuals with hemophilia A has dramatically improved over the past few decades, allowing for a better quality of life and preventing many of the serious complications associated with uncontrolled bleeding. Ongoing medical care, adherence to a treatment plan, and careful management of potential risks are essential for living well with hemophilia A. For more information, the National Bleeding Disorders Foundation provides excellent resources and support.
