Haemophilia

What is haemophilia?

Haemophilia (hemophilia) is an inherited bleeding disorder where the body lacks critical clotting factors to form blood clots.

The body has proteins called clotting factors which are involved in normal blood clot formation. When there is a deficiency of the clotting factors caused by abnormalities in the genes which are responsible for their production, this results in haemophilia. 

Without these clotting factors, the body is unable to stop bleeding effectively, which can lead to prolonged bleeding after injury, surgery or even spontaneously. One of the main concerns of the condition is internal bleeding, particularly into muscles and joints, which can cause pain, swelling, long-term damage and disability if not treated promptly.

What are the types of haemophilia?

There are three main types of haemophilia:

1. Haemophilia A (classical haemophilia): Caused by a deficiency of clotting factor VIII. It is the most common type, affecting about 80-85% of cases.
2. Haemophilia B (Christmas disease): Caused by a deficiency of clotting factor IX. It is less common, affecting about 15-20% of cases.
3. Haemophilia C: Caused by a deficiency of clotting factor XI. It is usually milder and affects both males and females.

What is the prevalence of haemophilia?

In Singapore, haemophilia is a rare inherited bleeding disorder. It primarily affects males, with an estimated local prevalence of about one in 5,000 to 10,000 male births for haemophilia A, and one in 30,000 to 50,000 male births for haemophilia B. The condition is much less common in females, as they are typically carriers rather than affected individuals.

Can haemophilia develop later in life?

Haemophilia is usually inherited, but in rare cases, an acquired form can develop due to an autoimmune condition where the body attacks clotting factors. This is more common in older adults and those with underlying medical conditions.

What are the symptoms of haemophilia?

​People with haemophilia may experience bleeding episodes that can occur spontaneously or after minor injuries. These symptoms often begin in early childhood and may vary in severity.

Common symptoms include:

• Prolonged bleeding after a cut, injury or surgery
• Frequent nosebleeds that are difficult to stop
• Easy bruising, often with large or deep bruises
• Bleeding into joints, causing pain, swelling and limited movement (commonly in knees, ankles and elbows)
• Bleeding into muscles, leading to swelling, pain and stiffness
• Blood in the urine or stool
• Prolonged bleeding after vaccinations or injections
• Head injuries may cause dangerous internal bleeding into the brain, even with minimal impact
• In babies:
  • Unexplained irritability or excessive crying (may indicate joint or muscle bleeds)
  • Noticeable swelling or bruising after crawling or learning to walk
    

When should you see a doctor?

Medical attention is necessary if you experience prolonged or unexplained bleeding, frequent nosebleeds, excessive bruising or swelling and pain in the joints. Seek immediate care if there is bleeding that does not stop, blood in the urine or stool or severe headaches following an injury, as these may indicate internal bleeding.

What are the potential complications of haemophilia?

The potential complications of haemophilia include:

• Joint damage: Repeated bleeding into joints can cause chronic pain, swelling and arthritis.
• Muscle damage: Bleeding into muscles may lead to swelling, nerve pressure and loss of function
• Internal bleeding: Life-threatening bleeds can occur in vital organs such as the brain or abdomen.
• Inhibitor development: Some people may develop antibodies (inhibitors) that prevent clotting factors from working properly.
• Anaemia: Chronic blood loss may result in low red blood cell levels.
• Infection risk: Older patients who received blood products before screening improvements may have been exposed to infections such as hepatitis C or HIV.

How is haemophilia prevented?

​Haemophilia is typically a genetic condition and cannot be prevented. For people who have a family history of haemophilia, genetic screening may be recommended prior to starting a family or during pregnancy to evaluate the risk of haemophilia in the child. 

What causes haemophilia?

Inherited haemophilia

Haemophilia is usually a genetic condition caused by a mutation in the genetic material of cells that make clotting factors, which are involved in the normal blood clotting process. This mutation can be passed from parents to their children.

Haemophilia is usually inherited in an X-linked recessive pattern, meaning the faulty gene is located on the X chromosome. Since males have one X and one Y chromosome, a single faulty gene on the X chromosome will result in the condition. Females have two X chromosomes, so they are typically carriers if only one X chromosome carries the mutation, and they may not have symptoms or may experience mild symptoms. A female carrier has a 50% chance of passing the faulty gene to her children.

Acquired haemophilia

In rare cases, haemophilia can be acquired. Acquired haemophilia occurs when the body’s immune system produces antibodies that mistakenly attack clotting factors, most commonly factor VIII. This form is not inherited and can occur in both males and females, often later in life. It may be associated with autoimmune conditions, cancer, pregnancy or certain medications.

What are the risk factors for haemophilia?

The biggest risk factor for haemophilia is having a family history of the condition. Haemophilia is an inherited disorder, usually passed down through families in an X-linked recessive pattern. This means that males born to mothers who are carriers have a high likelihood of being affected. Although rare, females may also be affected if both copies of the gene are altered.

Without a family history, the risk of developing haemophilia is extremely low.

What are the risk factors for complications from haemophilia?

While it is primarily inherited, certain factors can increase the risk of complications and worsening symptoms. Understanding these risk factors can help in managing the condition effectively.

• Trauma or surgery: Increases the risk of excessive or prolonged bleeding.
• Use of certain medications: Blood thinners and non-steroidal anti-inflammatory drugs (NSAIDs) can worsen bleeding tendencies.
• Inhibitor development: Some individuals develop antibodies against replacement clotting factors, reducing treatment effectiveness.
• Liver disease: Since the liver produces clotting factors, any impairment can worsen bleeding risks.
• Poor joint health: Repeated joint bleeds can lead to haemophilic arthropathy, causing pain and mobility issues.

How is haemophilia diagnosed?

The diagnosis of haemophilia involves identifying low levels of clotting factors and confirming genetic mutations. The following methods are commonly used:

• Measurement of clotting factor VIII or IX levels in the blood to determine severity
• Genetic testing to identify mutations in the F8 or F9 genes
• Prenatal diagnosis using chorionic villus sampling in early pregnancy for families with a known history of haemophilia
• Genetic screening of relatives to identify carriers and establish a complete family history

How is haemophilia treated?

Replacement therapy

All bleeding episodes have to be treated promptly by increasing the level of factor VIII or IX as necessary. Increasing blood factors can be achieved by infusion of commercially available factor concentrates.

Preparations of factor concentrates are made with pooled donor plasma (from many blood donors) or recombinant technology (from genetic manipulation of animal cells to produce human factors). The administration of factors can either be done by a medical professional, or taught to patients and/or their caregivers so that home treatment can be initiated.

The administration of foreign factor VIII or IX may at times lead to the development of antibodies against these factors which would require a change in treatment regimens.

Non-factor replacement drugs

Non-factor replacement drugs such as emicizumab are available to a select group of individuals with haemophilia. Instead of replacing the missing clotting factor directly, emicizumab acts like a helper that brings together other proteins in the blood to help it clot properly. It copies the job of factor VIII, which is usually missing or not working in people with haemophilia A. This helps prevent or reduce bleeding, even in those who do not respond well to regular treatment. Emicizumab is given as an injection and can make life easier by reducing the number of bleeds and hospital visits.

Antifibrinolytic agents

Antifibrinolytic agents such as tranexamic acid help stabilise clots and are particularly useful for mucosal bleeds.

Gene therapy

The use of gene therapy to correct the abnormal gene in haemophilia directly is currently being researched, and may be a treatment option in the near future.

References

Haemophilia Society UK. (n.d.). Haemophilia A and B. https://haemophilia.org.uk/bleeding-disorders/haemophilia-a-and-b/#:~:text=Haemophilia%20is%20a%20lifelong%2C%20inherited,normal%20for%20bleeding%20to%20stop.

Nature. (2021). Haemophilia: A primer. Nature Reviews Disease Primers, 7(1), Article 78. https://www.nature.com/articles/s41572-021-00278-x.

Wiley Online Library. (n.d.). Journal of Thrombosis and Haemostasis. https://onlinelibrary.wiley.com/journal/13652516.

World Federation of Hemophilia. (n.d.). World Federation of Hemophilia (WFH). https://wfh.org/.