Definition
Hemophilia is an inherited bleeding disorder in which a person lacks or has low levels of certain proteins called “clotting factors” and the blood doesn’t clot properly as a result. This leads to excessive bleeding. Bleeding disorders are due to defects in the blood vessels, the coagulation mechanism, or the blood platelets. An affected individual may bleed spontaneously or for longer than a healthy person after injury or surgery.
Why hemophilia is called the royal disease?
Hemophilia has often been called The Royal Disease. This is because Queen Victoria, Queen of England from 1837 to 1901, was a carrier. Her eighth child, Leopold, had hemophilia and suffered from frequent hemorrhages. These were reported in the British Medical Journal in 1868. Leopold died of a brain hemorrhage at the age of 31, but not before he had children. His daughter, Alice, was a carrier and her son, Viscount Trematon, also died of a brain hemorrhage in 1928.
Even more important to history was the existence of hemophilia in the Russian Royal Family. Two of Queen Victoria’s daughters, Alice and Beatrice, were also carriers of hemophilia. They passed the disease on to the Spanish, German and Russian Royal Families.
Alexandra, Queen Victoria’s granddaughter, married Nicholas, the Tsar of Russia in the early 1900’s. Alexandra, the Tsarina, was a carrier of hemophilia and her first son, the Tsarevich Alexei, a hemophiliac. Nicholas and Alexandra were pre-occupied by the health problems of their son at a time when Russia was in turmoil. The monk Rasputin gained great influence in the Russian court, partly because he was the only one able to help the young Tsarevich. He used hypnosis to relieve Alexei’s pain. The use of hypnosis not only relieved pain, but may have also helped slow or stop the boy’s hemorrhages. The illness of the heir to the Tsar’s throne, the strain it placed on the Royal Family, and the power wielded by the mad monk Rasputin were all factors leading to the Russian Revolution of 1917.
Types
The two most common types are hemophilia A and hemophilia B. Which one you have depends on which of the clotting factor proteins you are missing. Remember that people with hemophilia bleed longer because they can’t make a fibrin clot. They lack certain factor proteins needed to form the clot.
In hemophilia A, the missing factor protein is Factor VIII (“factor eight”). In hemophilia B, it is Factor IX (“factor nine”) that is missing.
Hemophilia A is also called:
- Factor VIII deficiency
- Classical Hemophilia
- Standard Hemophilia
Hemophilia B is also called:
- Factor IX deficiency
- Christmas disease
History
Hemophilia was recognized, though not named, in ancient times. The Talmud, a collection of Jewish Rabbinical writings from the 2nd century AD, stated that male babies did not have to be circumcised if two brothers had already died from the procedure.
The Arab physician Albucasis, who lived in the 12th century, wrote of a family whose males died of bleeding after minor injuries.
Then, in 1803, a Philadelphia physician named Dr. John Conrad Otto wrote an account of ‘a hemorrhagic disposition existing in certain families’. He recognized that the condition was hereditary and affected males. He traced the disease back through three generations to a woman who had settled near Plymouth, New Hampshire, in 1720.
The word hemophilia first appears in a description of the condition written by Hopff at the University of Zurich in 1828.
Epidemiology of hemophilia
The worldwide incidence is approximately 1 case per 5000 males, with approximately one third of affected individuals not having a family history of the disorder. The prevalence varies with the reporting country, with a range of 5.4-14.5 cases per 100,000 males. In the United States, the prevalence is 20.6 cases per 100,000 males. In 2016, the number of people in the United States with hemophilia was estimated to be about 20,000.
Hemophilia A occurs in all races and ethnic groups. In general, the demographics of hemophilia follow the racial distribution in a given population; for example, rates of hemophilia among whites, African Americans, and Hispanics in the US are similar.
Because it is an X-linked, recessive condition, it occurs predominantly in males. Females usually are asymptomatic carriers. However, mild symptoms may be more common in carriers than previously recognized. In 1 study, 5 of 55 patients (factor levels 5-50%) were girls.
Risk factors of hemophilia
Risk factors for include
- Family history of bleeding
- Male gender
Causes of hemophilia
When you bleed, your body normally pools blood cells together to form a clot to stop the bleeding. The clotting process is encouraged by certain blood particles (platelets and plasma proteins). Hemophilia occurs when you have a deficiency in one of these clotting factors.
It is inherited. However, about 30 percent of people with hemophilia have no family history of the disorder. In these people hemophilia is caused by a genetic change (spontaneous mutation).
There are several types of hemophilia. They are classified according to which clotting factor is deficient:
- Hemophilia A, the most common type, is caused by insufficient clotting factor VIII.
- Hemophilia B, the second most common type, is caused by insufficient clotting factor IX.
- Hemophilia C, in which signs and symptoms are often mild, is caused by insufficient clotting factor XI.
Symptoms
The extent of your symptoms depends on the severity of your factor deficiency. People with a mild deficiency may bleed in the case of trauma. People with a severe deficiency may bleed for no reason. This is called “spontaneous bleeding.” In children with this disease, these symptoms may occur around age 2.
Spontaneous bleeding can cause the following:
- blood in the urine
- blood in the stool
- deep bruises
- large, unexplained bruises
- excessive bleeding
- bleeding gums
- frequent nosebleeds
- pain in the joints
- tight joints
- irritability (in children)
Complications
The complications include:
- joint damage from repetitive bleeding
- deep internal bleeding
- neurological symptoms from bleeding within the brain
You’re also at an increased risk of developing infections, such as hepatitis, when you receive donor blood.
Diagnosis and tests
Hemophilia is diagnosed through a blood test. Your doctor will remove a small sample of blood from your vein and measure the amount of clotting factor present. The sample is then graded to determine the severity of the factor deficiency:
- Mild hemophilia is indicated by a clotting factor in the plasma that’s between 5 and 40 percent.
- Moderate hemophilia is indicated by a clotting factor in the plasma that’s between 1 and 5 percent.
- Severe hemophilia is indicated by a clotting factor in the plasma of less than 1 percent.
Treatment and medications
Treatment is very effective. The missing clotting factor is injected into the bloodstream using a needle. Bleeding stops when enough clotting factor reaches the spot that is bleeding. Bleeding should be treated as quickly as possible. Quick treatment will help reduce pain and damage to the joints, muscles, and organs. If bleeding is treated quickly, less blood product is needed to stop the bleeding.
Treatment products
Factor concentrates are the treatment of choice for hemophilia. They can be made from human blood (called plasma-derived products) or manufactured using genetically engineered cells that carry a human factor gene (called recombinant products). Factor concentrates are made in sophisticated manufacturing facilities. All commercially prepared factor concentrates are treated to remove or inactivate blood-borne viruses.
Cryoprecipitate is derived from blood and contains a moderately high concentration of clotting factor VIII (but not IX). It is effective for joint and muscle bleeds, but is less safe from viral contamination than concentrates and is harder to store and administer. Cryoprecipitate can be made at local blood collection facilities.
Fresh frozen plasma (FFP) the red cells have been removed, leaving the blood proteins including clotting factors VIII and IX. It is less effective than cryoprecipitate for the treatment of hemophilia A because the factor VIII is less concentrated. Large volumes of plasma must be transfused, which can lead to a complication called circulatory overload. FFP is still the only product available for treatment of hemophilia A and B in some countries.
People with this disease may sometimes use desmopressin (also called DDAVP) to treat minor bleeding. DDAVP is a synthetic hormone that stimulates the release of factor VIII.
Prevention
It is a condition that’s passed from a mother to her child. When you’re pregnant, there’s no way of knowing whether your baby has the condition. However, if your eggs are fertilized in a clinic using in vitro fertilization, they can be tested for the condition. Then, only the eggs without this can be implanted. Preconception and prenatal counseling can also help you understand your risk of having a baby with hemophilia.