What is Hemophilia A?
Hemophilia is a group of inherited bleeding disorders in which blood does not clot properly, and hemophilia A is the most common type. Also known as classic hemophilia or Factor VIII (FVIII) deficiency, this genetic condition arises from a problem with the F8 gene, which contains the instructions for making the Factor VIII clotting protein. In individuals with hemophilia A, this protein is either missing or present in insufficient or defective amounts. This deficiency prevents the formation of a stable blood clot, leading to prolonged bleeding, both externally and internally.
The Genetic Cause of Hemophilia A
For most people, hemophilia A is an inherited condition passed down from a parent to a child. The gene responsible, F8, is located on the X chromosome. Since males have one X and one Y chromosome, and females have two X chromosomes, the inheritance pattern is X-linked recessive. A male who inherits a mutated F8 gene on his single X chromosome will develop the disorder. Females, with two X chromosomes, can be carriers if one X chromosome has the mutated gene, as the other healthy X chromosome can often produce enough Factor VIII to prevent severe symptoms. However, female carriers can still have lower-than-normal Factor VIII levels and experience bleeding symptoms, particularly if their factor activity falls below 40%.
Approximately one-third of hemophilia A cases are caused by a spontaneous genetic mutation, where there is no previous family history of the disorder. In extremely rare instances, a person can develop acquired hemophilia A later in life, typically when the immune system mistakenly attacks clotting factor VIII.
Symptoms and Severity
The signs and symptoms of hemophilia A vary widely depending on the amount of functional Factor VIII in the blood, which is the basis for classifying severity.
- Mild hemophilia A: Individuals have 5% to 40% of the normal amount of Factor VIII. They typically only experience bleeding problems after major injuries, surgery, or dental work. In women, this can manifest as heavy menstrual bleeding.
- Moderate hemophilia A: Individuals have 1% to 5% of the normal Factor VIII level. They may experience spontaneous bleeding episodes, though less frequently than those with the severe form. Excessive bleeding can occur after minor trauma.
- Severe hemophilia A: Individuals have less than 1% of the normal Factor VIII level. This is the most common form of hemophilia A and often leads to frequent spontaneous bleeding episodes without apparent cause. Internal bleeding into joints, muscles, and organs is a major concern.
Common symptoms across all severity levels include:
- Easy bruising
- Frequent nosebleeds
- Unexplained or prolonged bleeding from cuts or injuries
- Bleeding into joints, causing pain, swelling, and tightness (leading to potential long-term damage)
- Blood in the urine or stool
- Painful, prolonged headaches or double vision, which can be signs of dangerous brain bleeds
Diagnosis of Hemophilia A
Diagnosis often begins with a thorough family history and a review of any unusual bleeding incidents. This is followed by a series of blood tests:
- Screening tests: The activated partial thromboplastin time (APTT) test measures how long it takes for a clot to form and will be prolonged in those with hemophilia A.
- Factor assay tests: If screening tests are abnormal, a specific clotting factor test, or assay, is performed to measure the level of Factor VIII activity in the blood. This confirms the diagnosis and determines the severity of the condition.
- Genetic testing: DNA tests can identify the specific F8 gene mutation, which is useful for family planning and carrier identification.
Treatment and Management
While there is no cure for hemophilia A, modern treatments allow most individuals to lead full and active lives. Treatment is typically managed at a specialized hemophilia treatment center.
Standard Treatment: Replacement Therapy
The most common treatment is the intravenous infusion of Factor VIII concentrates, which replaces the missing clotting factor.
- Prophylactic treatment: In severe cases, regular, scheduled infusions of Factor VIII concentrates are used to prevent bleeding episodes and reduce long-term joint damage.
- Episodic treatment: Infusions are given on demand to stop bleeding episodes when they occur.
Newer and Emerging Treatments
Recent years have seen the development of innovative therapies:
- Non-Factor Replacement Therapies: Emicizumab (Hemlibra®) is a medication that mimics the function of Factor VIII and is administered via subcutaneous injection, offering a less invasive treatment option.
- Gene Therapy: FDA-approved gene therapies, such as Roctavian®, offer a potential long-term solution by delivering a functional F8 gene to the body.
Living with Hemophilia A
Individuals with hemophilia A should take precautions to prevent injuries and be aware of their bleeding risk. Regular checkups with a hematologist are essential, and a personalized treatment plan is crucial for managing the condition. Avoiding certain medications, such as aspirin and NSAIDs, is important as they can increase bleeding.
| Feature | Mild Hemophilia A | Moderate Hemophilia A | Severe Hemophilia A |
|---|---|---|---|
| Factor VIII Level | 5%-40% of normal | 1%-5% of normal | <1% of normal |
| Spontaneous Bleeding | Rare | Less frequent | Frequent |
| Bleeding Trigger | Major injury or surgery | Minor trauma or surgery | Often no trigger required |
| Diagnosis Timing | Often later in life | Usually before age 5-6 | Often within the first year of life |
| Major Concern | Prolonged bleeding with procedures | Spontaneous joint and muscle bleeds | Frequent joint and muscle bleeds, organ damage |
For ongoing support and education, organizations such as the National Hemophilia Foundation offer valuable resources.
Conclusion
Hemophilia A, also known as classic hemophilia or Factor VIII deficiency, is a serious, lifelong genetic condition that impairs the blood's ability to clot. While the severity varies, proper diagnosis and consistent medical management are key to preventing life-threatening bleeds and long-term joint damage. With advancements in treatment, particularly with newer non-factor therapies and the emergence of gene therapy, individuals with hemophilia A can achieve a quality of life similar to those without the disorder.
