Kaushik Bharati, PhD
World Hemophilia Day is celebrated on 17th April every year. Supported by the World Federation of Hemophilia (WFH), this date has been chosen to honor Frank Schnabel, the founder of WFH, whose birthday falls on this date. This year’s theme is “Treatment for All: The Vision of All”. It is interesting to note that globally 1 in every 1,000 people suffer from a bleeding disorder (of which a major portion is attributed to hemophilia); most are not diagnosed and do not receive any treatment. Therefore, there is an urgent need to create awareness about this disease, and the World Hemophilia Day provides just that opportunity!
What is Hemophilia?
Hemophilia is a rare bleeding disorder where the blood doesn’t clot normally. If you have hemophilia, you’ll have a tendency to bleed longer following an injury. This bleeding can be both external as well as internal. External bleeding from small cuts is not so serious, but it’s the internal bleeding in the deep-seated tissues and organs that are dangerous. Internal bleeding can damage the affected tissues and organs. It can lead to extensive bruising on the skin, knees, ankles and elbows. In this disease, the patients have little or no clotting factors, as a result of which blood cannot clot if there is bleeding. So, the patient can literally bleed to death in the event of a serious injury. Therefore, we should keep in mind that this condition can be life-threatening.
What are the Types of Hemophilia?
There are two major types of hemophilia:
• Hemophilia A: This is the most common type of hemophilia and is also known as Classic Hemophilia. It occurs as a result of deficiency of Factor VIII, a clotting factor of blood.
• Hemophilia B: This is the second most common type of hemophilia and is also known as Christmas disease. It occurs as a result of deficiency of Factor IX, another clotting factor of blood.
• Hemophilia C: This is relatively less common and the symptoms are often mild. It is caused by deficiency of Factor XI.
Hemophilia A and B are clinically similar and are associated with spontaneous bleeding into the joints and muscles and internal or external bleeding after injury or surgery.
Approximately 1 in 5,000 males are born with hemophilia A, and 1 in 30,000 males are born with hemophilia B. All races and ethnic groups are affected. Hemophilia A is four times as common as hemophilia B. Importantly, more than half of hemophilia A patients suffer from severe form of the disease.
How Do You Get Hemophilia?
Hemophilia is usually inherited, meaning that it’s passed through a parent’s genes to their children. It is a historically established fact that Queen Victoria was a carrier and passed the mutation to her son Leopold, and through several of her daughters to members of the royal families of Spain, Russia, and Germany.
In approximately 30% hemophilia patients, the disease is not inherited, but occurs due to a mutation in the person’s own genes.
The X and Y chromosomes are known as the sex chromosomes as these determine the sex of an individual. A male inherits an X chromosome from his mother and a Y chromosome from his father. A female inherits an X chromosome from her mother and an X chromosome from her father.
The gene that causes hemophilia A and B is located on the X chromosome. Therefore, the gene cannot be passed from father to son. Hemophilia A or B almost universally occurs in boys and is passed from mother to son through one of the mother's genes. For each child, there is a 50% chance that a son will be hemophilic and a 50% chance that a daughter will carry the gene. Therefore, most women with the defective gene will be carriers and experience no signs or symptoms of hemophilia. However, some women may experience bleeding symptoms if their hemophilia-specific clotting factors become relatively low.
Hemophilia C can be passed from either parent to their offspring, so it can occur in both boys as well as girls.
What are the Symptoms of Hemophilia?
Symptoms of hemophilia usually vary with the degree of severity of the disease. If the clotting factors are mildly reduced, bleeding usually occurs only after insult or trauma such as surgery or severe injury. On the other hand, if the deficiency is severe, bleeding can occur spontaneously. The major signs and symptoms of hemophilia are as follows:
• Excessive bleeding from cuts, injuries, injections or following surgery.
• Frequent bleeding from nose.
• Bleeding from the mouth and gums
• Blood in urine or stool.
• Extensive bruising on skin.
• Deep bruising.
• Pain, swelling and tightness in the joints.
• Excessive irritability in children.
What are the Major Complications of Hemophilia?
Hemophilia can cause several severe complications. These are briefly highlighted below:
• Internal Bleeding: Widespread internal bleeding in the deep muscles can lead to swelling of the affected limb, leading to excessive pressure build-up and squeezing of nerves that can produce cramps, aches and severe pain. Internal bleeding can also exert pressure on joints that can lead to damage of the joints, and also cause arthritis.
• Susceptibility to Infections: Since, hemophilia patients are more likely to receive blood transfusions, there is a significant increase in the risk of infections due to substandard screening of the donated blood. Viral diseases like Hepatitis B and HIV/AIDS can spread to hemophilia patients through contaminated blood.
• Hypersensitivity Reactions: Hemophilia nowadays is treated by infusion of recombinant clotting factors. Under these circumstances, it is possible that the immune system can “over-react”, leading to hypersensitivity reactions that can cause damage to the tissues and organs of the patients.
How is Hemophilia Treated?
A number of strategies are employed to treat patients suffering from hemophilia. These are briefly highlighted below:
• Recombinant Clotting Factors: The blood clotting factors that are generally deficient in various forms of hemophilia, are nowadays manufactured by recombinant DNA technology or genetic engineering. Stringent quality control is exercised in the manufacturing process so that these recombinant products are not contaminated with pathogenic viruses. These recombinant clotting factors are the treatment of choice, particularly for long-term maintenance therapy in hemophilia patients.
• Cryoprecipitation: This is a method employed for concentrating Factor VIII, but is ineffective in case of Factor IX. Cryoprecipitates are generally effective for treating bleeding in the joints and muscles. However, the manufactured product is not as safe as the recombinant products, as contamination with viruses is a possibility. These products are also difficult to store and administer.
• Fresh Frozen Plasma: This product is manufactured by removing the red blood cells, while the plasma (containing the clotting factors) remains intact. This is freshly prepared and stored and transported in frozen condition. This is why it’s called fresh frozen plasma (FFP). FFP is less effective than cryoprecipitates as the concentration of Factor VIII is much less. However, in many countries, especially the developing countries, this is the only choice of treatment that is available.
• Desmopressin (DDAVP®): Desmopressin is a synthetic analog of the naturally occurring hormone vasopressin, and it stimulates the release of Factor VIII. This drug is sometimes recommended for treating minor bleeding in patients with mild hemophilia A.
How Can You Prevent Hemophilia?
It is indeed very difficult to assess the risk of occurrence of hemophilia in a child. However, consultation with a geneticist prior to conception, coupled with pre-natal diagnostic approaches may help prevent the occurrence of hemophilia.