What is Hemophilia? An NIH Perspective
Drawing from resources by the National Institutes of Health (NIH), including the National Heart, Lung, and Blood Institute (NHLBI) and MedlinePlus, hemophilia is a rare genetic bleeding disorder where the body's blood does not clot properly. The process of blood clotting relies on proteins called clotting factors. When a person has hemophilia, they either lack or have low levels of a specific clotting factor, which prevents the formation of a proper clot to stop bleeding. This can result in excessive, prolonged bleeding after an injury or surgery, and in severe cases, spontaneous internal bleeding can occur without an obvious cause.
This condition can significantly impact an individual's life, as internal bleeding can cause serious complications, including damage to joints, muscles, and organs. While often inherited, it is important to note that a rare, non-inherited form known as acquired hemophilia also exists, where the immune system attacks a clotting factor.
The Types and Causes of Hemophilia
Hemophilia is primarily categorized into types A and B, which are caused by genetic mutations affecting different clotting factors. For both types, the gene is located on the X chromosome, explaining why the condition is far more prevalent in males.
Hemophilia A This is the most common form of the disorder, affecting about 1 in 4,000 to 1 in 5,000 males. It is caused by a deficiency in clotting factor VIII (8). Hemophilia A can range from mild to severe, depending on the level of factor VIII activity.
Hemophilia B (Christmas Disease) This type is less common, affecting approximately 1 in 20,000 newborn males. It results from a deficiency of clotting factor IX (9). Like hemophilia A, the severity of hemophilia B depends on the amount of functional factor IX a person has.
Acquired Hemophilia This is a rare autoimmune disorder where a person's immune system spontaneously produces autoantibodies that attack and disable a clotting factor, most often factor VIII. It is not inherited and can occur at any age, sometimes triggered by pregnancy, immune system disorders, or cancer.
Comparison Table: Hemophilia A vs. B
| Feature | Hemophilia A | Hemophilia B |
|---|---|---|
| Missing Clotting Factor | Factor VIII (8) | Factor IX (9) |
| Prevalence | More common (1 in 4,000-5,000 males) | Less common (1 in 20,000 males) |
| Genetics | X-linked recessive | X-linked recessive |
| Alternative Name | Classic Hemophilia | Christmas Disease |
| Severity | Mild, moderate, or severe | Mild, moderate, or severe |
Signs, Symptoms, and Diagnosis
The severity of hemophilia and its symptoms can vary based on the level of clotting factor activity. Individuals with a mild form might only experience excessive bleeding after major surgery or trauma. In contrast, those with severe hemophilia may have spontaneous bleeding episodes for no obvious reason.
Common Signs and Symptoms
- Unexplained and excessive bleeding from cuts, injuries, or after surgery.
- Many large or deep bruises.
- Pain, swelling, or tightness in joints, often in the knees, elbows, and ankles.
- Blood in the urine (hematuria) or stool.
- Frequent nosebleeds.
- Unusual bleeding after dental work.
- For infants, large bruises from minor movements or excessive bleeding after circumcision.
Serious Bleeding Episodes Internal bleeding in vital areas like the brain is a major concern, particularly for those with severe hemophilia. Symptoms can include:
- Prolonged, painful headaches.
- Repeated vomiting.
- Sleepiness or changes in behavior.
- Sudden weakness or clumsiness.
- Double vision or convulsions.
How is Hemophilia Diagnosed?
Diagnosis typically begins with a review of personal and family medical history and a physical examination. Laboratory tests are then conducted to confirm the diagnosis and determine the type and severity:
- Coagulation tests: A blood test, such as an activated partial thromboplastin time (aPTT), measures how long it takes for a person's blood to clot. An isolated prolonged aPTT is a key indicator for acquired hemophilia.
- Clotting factor assays: These specific tests measure the level and activity of factor VIII and factor IX in the blood, confirming the type of hemophilia.
Treatment and Management of Hemophilia
Treatment has advanced significantly, allowing most people with hemophilia to live healthy, active lives. The main treatment for congenital hemophilia involves replacing the missing clotting factor.
Factor Replacement Therapy
This treatment involves infusing (injecting) commercially prepared clotting factor concentrates into a vein.
- Plasma-derived concentrates: Made from proteins found in human plasma. Modern screening techniques have minimized the risk of viral transmission.
- Recombinant concentrates: Genetically engineered in a lab without using human plasma, further reducing the risk of bloodborne viruses.
Replacement therapy can be administered in two ways:
- Prophylactic care: Regular infusions to prevent bleeding episodes.
- Episodic (on-demand) care: Infusions to treat a bleeding episode as it occurs.
Other Therapies
- Desmopressin (DDAVP): A hormone that can stimulate the body to release stored factor VIII in individuals with mild hemophilia A.
- Emicizumab (Hemlibra): A non-factor, bispecific antibody that helps restore the clotting process in people with hemophilia A, with or without inhibitors. It is administered via subcutaneous injection.
- Antifibrinolytic agents: Medications that prevent clots from breaking down, often used for mouth or nosebleeds.
Gene Therapy and Future Directions
Gene therapy offers the potential for a long-term, possibly one-time, treatment by providing a functional copy of the faulty gene to liver cells, enabling the body to produce its own clotting factor.
Recent FDA-approved gene therapies for adults include:
- Roctavian® for severe hemophilia A.
- Hemgenix® for hemophilia B.
The NIH and other organizations continue to fund research into gene therapy and other novel treatments to improve outcomes and address challenges like immune responses (inhibitors).
Living Well with Hemophilia
Managing life with hemophilia requires proactive care and education. People with hemophilia are often encouraged to seek care from a comprehensive hemophilia treatment center (HTC), where they can access a multidisciplinary team of specialists.
Practical Tips
- Annual Checkups: Regular visits to an HTC are linked to better long-term health outcomes.
- Safe Exercise: Low-impact activities like swimming, walking, and cycling strengthen muscles and protect joints. High-impact contact sports should typically be avoided.
- Emergency Plan: Develop a plan detailing what to do during a bleeding emergency, and ensure family and friends are aware.
- Dental Care: Good hygiene is important to prevent dental procedures that might cause significant bleeding.
- Avoid Medications: Certain over-the-counter pain relievers, like aspirin and ibuprofen, can worsen bleeding and should be avoided.
- Emotional Support: Connecting with patient advocacy groups can provide valuable support and resources.
For more information on the latest research and clinical trials, the NIH provides extensive resources. Learn more at the Clinical Trials.gov website.
Conclusion
Hemophilia, a complex bleeding disorder, is a subject of significant research and improved treatment options, thanks to ongoing efforts supported by institutions like the NIH. Understanding the disorder's genetic basis, symptoms, and the range of available therapies is vital for effective management. With advancements in care, particularly the emergence of gene therapy, individuals with hemophilia can look forward to a future with fewer bleeding episodes and an improved quality of life. Accessing comprehensive care at an HTC and following preventive measures remain key components of living well with this condition.
