Have you noticed some people have a tendency to bruise easily especially in early childhood or have excessive bleeding from cuts that takes a long time to stop? Sounds like a very common condition, doesn’t it? We all have someone we know who is extra “wobbly” or gets through 5-6 bandaids a day. What we are unaware of is that there is a certain population of people that exhibit these symptoms and suffer from a well-known genetic bleeding disorder known as Haemophilia.
Know more about it
Haemophilia A is a bleeding disorder caused by the absence of the protein essential for making a blood clot. This protein is also known as the clotting factor: Haemophilia A is caused by a deficiency of clotting factor VIII (eight) whereas Haemophilia B is caused by a deficiency of clotting factor IX (nine).
Haemophilia A and B are both genetic conditions and most cases are identified at a stage as early as birth. In around two-thirds of cases, there is a family history of haemophilia A. The remaining cases are caused by spontaneous mutations.
Haemophilia A and B mainly affects males. Females can be ‘carriers’ of the affected gene and may experience symptoms.
The clinical phenotype of Haemophilia may vary from mild (5-40% clotting factor activity), to moderate (1-5% clotting factor activity) to severe (<1% clotting factor activity) and can be determined through blood tests. 25-30% of haemophilic individuals may produce inhibitory antibodies, which act against the clotting factor protein administered during therapy. This is a major complication in haemophilia treatment and has been reported in specific populations that may carry other immune-related gene variants, too.
What causes this condition? Is it genetic?
Haemophilia is caused by a mutation in genes responsible for making the clotting factor proteins. These genes are located on the X chromosome. Males have one X and one Y chromosome (XY) and females have two X chromosomes (XX). The X chromosome in males comes from their mothers and the Y chromosome from their fathers. Females inherit one X chromosome from each parent.
Thus, males can develop haemophilia if they inherit an affected X chromosome that has a mutation in either the factor VIII or factor IX gene. Females also have the possibility of developing the disease, but cases are much rarer. In those cases, both X chromosomes have to be affected or one is affected and the other is inactive. Females with this set show bleeding symptoms similar to males with haemophilia.
A female with one affected X chromosome is a “carrier” of haemophilia. There are cases where a carrier could have symptoms of haemophilia as well. In addition, she has the ability to pass the affected X chromosome with a gene mutation on to her children!
Even though haemophilia does run in families, certain families have no prior history. Sometimes, there are carrier females in the family, but no affected boys. Haemophilia can result in:
- Bleeding within joints that lead to chronic joint disease and pain
- Bleeding in the head causes seizures and paralysis
- Excessive bleeding to vital organs such as the brain can cause death too!
Facts and Stats
The worldwide incidence of haemophilia is not well known, but estimated at more than 400,000 people.
There is currently no cure for the condition. There are very effective treatments available in the US, but require the lifelong infusion of drugs manufactured from human plasma or through recombinant biotechnology.
Nearly 90% of Americans with severe haemophilia became infected with AIDS in the 1980s when blood and plasma donations in the US were not properly screened for HIV.
Recent research and technology in donor screening and viral inactivation measures in the commercial manufacturing process have made clotting factor products very safe.
Acquired haemophilia is rarer, with an incidence of 1.34 cases per million population a year.
Early Detection and Genetic Diagnosis
In cases of known family history, families with haemophilia get their baby boys tested soon after birth. About one-third of babies diagnosed with haemophilia show a new mutation that is absent in their family members. In these cases, blood tests help confirm if the blood is clotting properly. Factor assays help determine the cause of the bleeding disorder. These tests help evaluate the type of haemophilia and the severity. It is also possible to find your probability of being a carrier. Some carrier analysis tests that can help include:
- Hemophilia-A Carrier analysis at intragenic markers (BclI & XbaI RFLP)
- Hemophilia-B-Carrier analysis at intragenic markers (HhaI, DdeI, TaqI)
What are the options for cure and treatment?
Haemophilia is treated by replacing the missing blood clotting factor so that the blood can clot properly. This is done by infusing commercially prepared factor concentrates. People with haemophilia can learn how to perform these infusions themselves so that they can stop bleeding episodes and, by performing the infusions on a regular basis (called prophylaxis), can even prevent most bleeding episodes.
Haemophilia Treatment Centers (HTC) offer good quality medical care from doctors and nurses well versed with this disorder and can help prevent serious issues. An HTC not only provides care to address all issues related to the disorder, but also provides health education that helps people with the condition to stay healthy.
A word from us
Families with Haemophilia history should be genetically tested.
- Consider Genetic counselling before family planning
- Cuts and open wounds should be treated with caution
- Learn and spread knowledge about the severity of the condition
Although rare, this condition is among the top six bleeding disorders in India. The reported number of patients with haemophilia A is 11,586 while the estimated prevalence could be around 50,000 patients. Our country does not have a policy on the prevention and control of such genetic disorders. Hence, it is even more important to create awareness on such dedicated days.
About the Author
Dr. Pallavi Jain is part of the Scientific Team at Mapmygenome. She has a Bachelors Degree in Biochemistry with Genetics and a PhD in Molecular Medicine (UK). She recently completed an intensive course in IVF from Origio, Mumbai. She enjoys swimming and reading.