Causes of Haemophilia
The causes of Haemophilia are rooted in a genetic mutation that impairs the body’s ability to produce specific clotting factors essential for normal blood coagulation. In most cases, the causes of Haemophilia can be traced to inherited mutations passed from mother to son, but spontaneous mutations or acquired forms may also occur.
Haemophilia is a classic example of a genetic bleeding disorder, where a single faulty gene disrupts a vital physiological process. This condition highlights the importance of the clotting cascade, a highly coordinated system that, when impaired, leads to dangerous and prolonged bleeding episodes.
1. Genetic Inheritance
Haemophilia A and B are inherited in an X-linked recessive pattern:
Males have one X and one Y chromosome. If the X chromosome carries the defective gene, they will express the disease.
Females have two X chromosomes. If one X has the defective gene, they are typically carriers and usually asymptomatic, though some may show mild symptoms if the working gene is underexpressed.
A carrier mother has a:
50% chance of passing the defective gene to her sons (who will have the disease)
50% chance of passing it to her daughters (who will become carriers)
In families with no known history, up to one-third of cases are due to spontaneous mutations.
2. Mutations in Specific Genes
Haemophilia results from mutations in:
The F8 gene (on the X chromosome) for Haemophilia A
The F9 gene (also on the X chromosome) for Haemophilia B
These genes provide instructions for making clotting factors VIII and IX respectively. Mutations can vary:
Point mutations
Insertions or deletions
Inversions, such as the intron 22 inversion in Haemophilia A, which is common in severe cases
The nature of the mutation often influences the severity of the condition. Some mutations lead to no functional protein being produced, while others result in a less active version.
3. Carrier Status and Mild Haemophilia in Females
While traditionally considered male-only, some female carriers may experience:
Heavy menstrual bleeding
Bleeding after dental work or surgery
Easy bruising
This is due to lyonisation (random X-chromosome inactivation), where the working gene may be inactive in a significant number of cells.
Female carriers should be assessed for factor levels and receive appropriate counselling and management, especially during childbirth or surgical procedures.
4. Acquired Haemophilia
In contrast to inherited forms, acquired Haemophilia is caused by:
Autoantibodies that neutralise factor VIII (rarely factor IX)
Often appears later in life, typically after age 60
Can also occur postpartum or in association with autoimmune diseases, cancer, or drug reactions
Unlike inherited Haemophilia, acquired Haemophilia affects both men and women and can lead to severe bleeding despite no family history.
5. Gene Therapy and Genetic Testing
Understanding the genetic basis of Haemophilia has enabled the development of:
Gene therapy, where a healthy version of the clotting factor gene is inserted using viral vectors
Preimplantation genetic diagnosis (PGD), which allows carrier parents to screen embryos for Haemophilia mutations
Prenatal testing, including amniocentesis and chorionic villus sampling (CVS)
Families with a history of Haemophilia benefit from early genetic counselling to understand inheritance risks and testing options.
6. Spontaneous Mutations
Around 30% of Haemophilia cases occur with no known family history, due to new mutations in the F8 or F9 gene. These may arise:
During sperm or egg formation
In the embryo after conception
Such mutations are unpredictable but carry the same risk of inheritance in future generations.
Summary Table: Causes of Haemophilia
| Cause | Description |
| Inherited X-linked mutation | Defective F8 or F9 gene passed from carrier mothers |
| Spontaneous mutation | New mutation with no family history |
| Acquired antibodies | Autoimmune reaction neutralising clotting factors |
| Lyonisation in carriers | Inactivation of healthy X gene in female carriers |
7. Misconceptions About Causes
Common myths include:
Haemophilia is caused by an injury – it is not; it is genetic or autoimmune
All cases are inherited – not true; many arise spontaneously
Women can’t have Haemophilia – false; some women experience mild symptoms or acquired forms
Public education and medical awareness are essential in dispelling these myths.
Conclusion | Causes of Haemophilia
The causes of haemophilia are mostly genetic. In most cases, it happens because of a mutation in the gene that controls the production of clotting factor VIII (in Haemophilia A) or factor IX (in Haemophilia B). These mutations are usually passed down through families in an X-linked recessive pattern. This means the condition mostly affects males, while females can be carriers.
However, in some cases, haemophilia can also result from a new or spontaneous gene mutation, with no family history. Either way, the result is the same—blood doesn’t clot properly, which increases the risk of prolonged or internal bleeding.
By understanding what causes haemophilia, doctors can diagnose the condition early, create effective treatment plans, and offer genetic counselling to help families understand the risks and options for the future.
