Hemophilia A and B are inherited in an X-linked recessive genetic pattern and are therefore much more common in males. This pattern of inheritance means that a given gene on the X chromosome expresses itself only when there is no normal gene present. For example, a boy has only one X chromosome, so a boy with hemophilia has the defective gene on his sole X chromosome (and so is said to be hemizygous for hemophilia). Hemophilia is the most common X-linked genetic disease.
Although it is much rarer, a girl can have hemophilia, but she would have to have the defective gene on both of her X chromosomes or have one hemophilia gene plus a lost or defective copy of the second X chromosome that should be carrying the normal genes. If a girl has one copy of the defective gene on one of her X chromosomes and a normal second X chromosome, she does not have hemophilia but is said to be heterozygous for hemophilia (a carrier). Her male children have a 50% chance of inheriting the one mutated X gene and thus has a 50% chance of inheriting hemophilia from their carrier mother.
Hemophilia A occurs in about 1 out of every 5000 live male births. Hemoplilia A and B occurs in all racial groups. Hemophilia A is about four times more common than B. B occurs in about 1 out of 20- 30,000 live male births.
Hemophilia has been called the Royal Disease because Queen Victoria, Queen of England from 1837 to 1901, was a carrier. Her daughters passed the mutated gene on to members of the royal families of Germany, Spain, and Russia. Alexandra, Queen Victoria's granddaughter, who became Tsarina of Russia in the early 20th century when she married Tsar Nicholas II, was a carrier. Their son, the Tsarevich Alexei, suffered from hemophilia.Hemophilia facts
Hemophilia is one of a group of inherited bleeding disorders that cause abnormal or exaggerated bleeding and poor blood clotting.
Hemophilia A and B are inherited in an X-linked recessive genetic pattern, so males are commonly affected while females are usually carriers of the disease.
Hemophilia A is caused by a deficiency of clotting Factor VIII, while hemophilia B (also called Christmas disease) results from a deficiency of Factor IX.
Hemophilia varies in its severity among affected individuals.
Symptoms include excessive bleeding from any site in the body; long-term damage to joints from repeated bleeding episodes is characteristic.
Treatment involves coagulation factor replacement therapy.
The formation of inhibitors to the treatment factor concentrates is a significant complication of treatment.
Gene therapy treatments are a source of active research and hold promise for the future.What causes hemophilia?
As mentioned above, hemophilia is caused by a genetic mutation. The mutations involve genes that code for proteins that are essential in the blood clotting process. The bleeding symptoms arise because blood clotting is impaired.
The process of blood clotting involves a series of complex mechanisms, usually involving 13 different proteins classically termed factors I through XIII and written with Roman numerals. If the lining of the blood vessels becomes damaged, platelets are recruited to the injured area to form an initial plug. These activated platelets release chemicals that start the clotting cascade, activating a series of 13 proteins known as clotting factors. Ultimately, fibrin is formed, the protein that crosslinks with itself to form a mesh that makes up the final blood clot. The protein involved with hemophilia A is factor VIII (factor 8) and with hemophilia B is factor IX (factor 9).
Picture of the blood clotting process
Picture of the blood clotting process
Hemophilia A is caused by a mutation in the gene for factor VIII, so there is deficiency of this clotting factor. Hemophilia B (also called Christmas disease) results from a deficiency of factor IX due to a mutation in the corresponding gene.
A condition referred to as hemophilia C involves a deficiency of clotting factor XI. This condition is much rarer than hemophilia A and B and typically leads to mild symptoms. It is also not inherited in an X-linked manner and affects persons of both sexes.
Hemophilia A is more common than hemophilia B. About 80% of people with hemophilia have hemophilia A. Hemophilia B occurs in about 1 out of every 20,000 to 30,000 people. A subgroup of those with hemophilia B has the so-called Leyden phenotype, which is characterized by a severe hemophilia in childhood that improves at puberty.Symptoms of Hemophilia
The main symptom of hemophilia is that once bleeding starts the child bleeds longer than normal.
Hemophilia symptoms can range from mild to severe. This depends on how low the level of the clotting protein is.
Some people with mild hemophilia may not even know they have the disease until adulthood. Minor injuries may not cause any noticeable problem. It may take a major trauma or surgery to cause enough bleeding that the problem becomes known.
On the other hand, someone with severe hemophilia may frequently bleed without any known reason or injury. This is called "spontaneous" bleeding. Sometimes this type of bleeding occurs in a joint, like the knee or elbow, which can be quite painful.
Symptoms of hemophilia may include:
Nosebleeds
Bruising, especially a large, lumpy bruise
Bleeding for no known reason
Blood in the urine or stool
Bleeding that does not stop after getting a cut, having a tooth out, getting an injury to the mouth or having surgery
Bleeding that does not stop after circumcision
Bleeding into a joint, which can cause tightness, swelling and pain
Hemophilia Diagnosis
If your child seems to have a bleeding problem, the doctor will ask questions about your child's bleeding and about your family history of unusual bleeding or bruising. The doctor will also examine your child to look for any other signs of health problems.
Blood tests will show your child's levels of Factor VIII and Factor IX. The doctor can tell you whether the hemophilia is mild, moderate or severe based on the levels of these clotting factors. This is the standard breakdown:
Mild - Your child has 5% to 30% of the normal level of Factor VII or IX.
Moderate - Your child has 1% to 5% of the normal level.
Severe - Your child has less than 1% of the normal level.
The level of clotting factor gives you a basic idea of how severe your child's symptoms might be - with less severe symptoms occurring in people who have higher levels of clotting factor. But they lines are not always clear. Some people with "mild" hemophilia have more severe symptoms than others.
Talk with your child's doctor to get a better idea of what the diagnosis means for your child.
The major signs and symptoms of hemophilia are excessive bleeding and easy bruising.
Excessive Bleeding
The extent of bleeding depends on how severe the hemophilia is.
Children who have mild hemophilia may not have signs unless they have excessive bleeding from a dental procedure, an accident, or surgery. Males who have severe hemophilia may bleed heavily after circumcision.
Bleeding can occur on the body's surface (external bleeding) or inside the body (internal bleeding).
Signs of external bleeding may include:
Bleeding in the mouth from a cut or bite or from cutting or losing a tooth
Nosebleeds for no obvious reason
Heavy bleeding from a minor cut
Bleeding from a cut that resumes after stopping for a short time
Signs of internal bleeding may include:
Blood in the urine (from bleeding in the kidneys or bladder)
Blood in the stool (from bleeding in the intestines or stomach)
Large bruises (from bleeding into the large muscles of the body)
Bleeding in the Joints
Bleeding in the knees, elbows, or other joints is another common form of internal bleeding in people who have hemophilia. This bleeding can occur without obvious injury.
At first, the bleeding causes tightness in the joint with no real pain or any visible signs of bleeding. The joint then becomes swollen, hot to touch, and painful to bend.
Swelling continues as bleeding continues. Eventually, movement in the joint is temporarily lost. Pain can be severe. Joint bleeding that isn't treated quickly can damage the joint.
Bleeding in the Brain
Internal bleeding in the brain is a very serious complication of hemophilia. It can happen after a simple bump on the head or a more serious injury. The signs and symptoms of bleeding in the brain include:
Long-lasting, painful headaches or neck pain or stiffness
Repeated vomiting
Sleepiness or changes in behavior
Sudden weakness or clumsiness of the arms or legs or problems walking
Double vision
Convulsions or seizures