Haemophilia is an X-linked condition, with the gene mutation located on the X chromosome. Since males have one X and one Y chromosome (XY) and females have two X chromosomes (XX), the inheritance patterns differ between genders. A male with the haemophilia gene mutation on his X chromosome will have the condition, while a female carrier with the mutation on one X chromosome usually does not exhibit symptoms due to the presence of a normal second X chromosome.

The inheritance details are as follows:

• A carrier mother has a 50% chance of passing the gene to her children, meaning her sons have a 50% chance of having haemophilia and her daughters have a 50% chance of being carriers.
• A father with haemophilia will pass his normal Y chromosome to his sons (making them unaffected) and his affected X chromosome to his daughters (making them carriers).
• In the rare instance that both parents carry the haemophilia gene, there is a 50% chance their daughter will have haemophilia.
  

Approximately 30% of haemophilia cases arise from a spontaneous mutation, with no family history of the condition¹.

Source: ¹National Hemophilia Foundation

Signs of haemophilia include easy bruising and spontaneous joint or muscle bleeds without significant injury. The most severe bleeding occurs in the brain and abdomen, which can be life-threatening and lead to permanent disabilities.

Haemophilia is a genetic disorder that can be present from birth. However, signs of bleeding typically become evident after an injury. In newborns, bleeding complications may arise during or shortly after birth, particularly following a prolonged or complicated delivery. Children with severe haemophilia often display excessive bruising when they begin to crawl and experience joint bleeds as they start walking. Milder forms of haemophilia may not become apparent until later in childhood or adolescence.

There is no cure for haemophilia. However, it can be managed effectively with factor replacement therapy. This treatment involves injecting the missing clotting factor—Factor VIII for Haemophilia A or Factor IX for Haemophilia B—directly into the bloodstream. Treatment approaches include:

1. Prophylactic (Preventive) Therapy:
   Regular injections of the clotting factor are administered to prevent bleeds, especially in children with severe haemophilia, who are at risk of spontaneous bleeding.
2. On-demand Therapy:
   Injections are given in response to bleeding episodes, often indicated by joint swelling, warmth or pain.

The dosage of Factor VIII or IX concentrate is determined by the child's weight and the severity of the bleed and must be prescribed by a doctor haematology specialist. Parents may keep a supply at home for immediate use, with instruction on proper storage and administration provided for home therapy.

Children with hard-to-access veins may require a portacath—a device implanted under the skin that allows easy access to a central vein for medication administration. The portacath may need replacement if it becomes blocked or infected and typically lasts 2 to 3 years.

In cases of severe internal bleeding, such as brain or abdomen bleeds, emergency hospital treatment with high-dose factor replacement therapy is essential.

Inhibitors

Some children develop inhibitors—antibodies that neutralise the clotting factor, rendering replacement therapy ineffective. This occurs in approximately 20–30% of individuals with Haemophilia A² and 3% with Haemophilia B³ undergoing factor replacement therapy. The risk of inhibitor development is linked to the type of genetic mutation present.

Managing haemophilia with inhibitors is challenging. For individuals with low levels of inhibitors, higher doses of factor concentrate may be effective in controlling bleeding. On the contrary, patients with high levels of inhibitors require bypassing agents like Factor Eight Inhibitor Bypassing Activity (FEIBA).

Immune Tolerance Induction (ITI) therapy is another approach, involving daily high-dose factor concentrate administration until inhibitors are eradicated. ITI is successful in about 70% of patients with Haemophilia A⁴ ,typically taking 6 to 12 months to achieve success.

Source: ²American Journal of Hematology, ³British Journal of Haematology, ⁴Journal of Thrombosis and Haemostasis

Children with haemophilia should avoid contact sports and activities posing a risk of abdomen or head injury due to the severe consequences of internal bleeding. Nonetheless, they are encouraged to engage in suitable physical activities, like swimming and non-contact sports, to strengthen joints and muscles, reducing the likelihood of bleeds. Those on prophylactic replacement therapy may safely participate in more vigorous exercise and enjoy a normal lifestyle.

Families are educated about early bleeding signs to promptly administer factor concentrate injections at home. It is important to avoid medications that worsen bleeding, such as aspirin and warfarin.

Useful Links

• World Federation of Haemophilia
  World Federation of Haemophilia is an international not-for-profit organization that was established in 1963.
• Haemophilia Society of Singapore
  This is the website of the Singapore haemophilia patient support group.

Continued clinical research is essential for advancing paediatric healthcare. Our doctors are committed to contributing to the future of child health and medicine through both clinical practice and research.

• Ng HJ, Lam J, Koh PL, Ho L, Lim CY, Akhbar Ali M, . . . Tien SL (2015). A comprehensive study of current haemophilia care and outcomes in Singapore. Haemophilia : the official journal of the World Federation of Hemophilia, 21(5):e428-31. doi: 10.1111/hae.12729