Hemophilia
Hemophilia is a genetic disorder caused by missing or defective factor, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases found have no previous family history.
According to the US Centers for Disease Control and Prevention (CDC), hemophilia occurs in approximately 1 in 5,617 live male births. There are between 30,000 – 33,000 males with hemophilia in the US. More than half of people diagnosed with hemophilia A have the severe form. Hemophilia A is four times as common as hemophilia B. Hemophilia affects all races and ethnic groups.
How is Hemophilia Inherited?
Hemophilia is passed down from parents to children.
Is Hemophilia Sex linked?
Yes, hemophilia is a sex-linked disorder. The X and Y sex chromosomes help determine hemophilia inheritance patterns. The gene for hemophilia is carried on the X chromosome.
Is Hemophilia Dominant or Recessive?
Hemophilia is inherited in an X-linked recessive manner. Females inherit two X chromosomes, one from their mother and one from their father (XX). Males inherit an X chromosome from their mother and a Y chromosome from their father (XY). That means if a son inherits an X chromosome carrying hemophilia from his mother, he will have hemophilia. It also means that fathers cannot pass hemophilia on to their sons. But because daughters have two X chromosomes, even if they inherit the hemophilia gene from their mother, most likely they will inherit a healthy X chromosome from their father and not have hemophilia. A daughter who inherits an X chromosome that contains the gene for hemophilia is called a carrier. She can pass the gene on to her children. Many women who carry the hemophilia gene also have low factor expression, which can result in heavy menstrual bleeding, easy bruising, and joint bleeds.
Some women who have the hemophilia gene have factor expression low enough to be diagnosed with hemophilia.
What are the severity rates?
- Severe (factor levels less than 1%)
- Moderate (factor levels of 1-5%)
- Mild (factor levels of 6%-30%)
What are the symptoms?
People with hemophilia bleed longer than other people. Bleeds can occur internally, into joints and muscles, or externally, from minor cuts, dental procedures, or injuries. How often a person bleeds, and the severity of those bleeds depends on how much factor a person produces naturally.
Normal levels of factor range from 50% to 150%. Levels below 50% – or half of what is needed to form a clot – determine a person’s symptoms.
How is Hemophilia diagnosed?
Doctors will perform tests that evaluate how long it takes for the blood to clot to determine if someone has hemophilia. A clotting factor test, called an assay, will show the type of hemophilia and the severity, or how much clotting factor the person produces on their own.
Because of our understanding of hemophilia genetics, most people who have a family history of hemophilia will ask that their baby boys be tested soon after birth to see if they have hemophilia. If there is no family history of hemophilia, people often notice bleeding that takes longer to stop or lots of bruising. Many babies born with severe hemophilia are diagnosed if there is prolonged bleeding after circumcision.
For girls, it often takes seeing worsening of symptoms for the diagnosis process to begin. Most girls are not tested for hemophilia before puberty. Heavy periods are a symptom of a bleeding disorder in women and girls. If there is a known family history, it is important to monitor for symptoms. It is recommended that women who have a family history of hemophilia get tested before getting pregnant, to help prevent complications during childbirth.
The best place for patients with hemophilia to be diagnosed and treated is at one of the federally funded hemophilia treatment centers (HTCs) that are spread throughout the country. HTCs provide comprehensive care from skilled hematologists and other professional staff, including nurses, physical therapists, social workers and sometimes dentists, dietitians and other healthcare providers, including specialized labs for more accurate lab testing.
What are different types of treatment?
Most treatments for hemophilia focus on replacing the missing protein, so a person can form a clot, to reduce or eliminate the bleeds associated with the disorder. Treatments that work to prevent bleeding through new mechanisms have recently come to the market or are undergoing evaluation in research studies. People with hemophilia have several different medication options for treatment.
Von Willebrand Disease
Von Willebrand disease (VWD) is an inheritable, factor-deficient bleeding disorder. Many different proteins are needed to make a person’s blood clot successfully. People with VWD are either missing or low in the clotting protein von Willebrand factor (VWF) – or it doesn’t work as it’s supposed to. For a person to make a successful clot, VWF binds to factor VIII (8), another clotting protein, and platelets in blood vessel walls. This process will help form a platelet plug during the clotting process. People with VWD are not able to form this platelet plug, or it will take longer to form. T
VWD is the most common bleeding disorder, affecting up to 1% of the US population – or approximately 1 in every 100 people. It occurs equally in men and women. However, women may be more symptomatic due to heavy menstrual bleeding (periods). VWD occurs equally across all races and ethnicities.
What are the symptoms?
- The main symptoms of VWD are:
- Frequent (more than 5 a year) nosebleeds that last longer than 10 minutes
- Bleeding from cuts or injuries that lasts longer than 10 minutes
- Bruising easily, with bruises that are raised and larger than a quarter
- Being told you are “low in iron” or have been treated for anemia.
- Heavy bleeding after any surgery including dental surgery
- Having someone in your family who has one or more of these symptoms
- Have someone in your family who has been diagnosed with a bleeding disorder such as von Willebrand disease or hemophilia.
- For women, girls and those who menstruate:
- Heavy periods, also called heavy menstrual bleeding, (having to change one pad or tampon every hour) or periods that last longer than 7 days
- Heavy bleeding after childbirth or miscarriage
What are the types of VWD?
There are three main types of VWD. A fourth type, acquired VWD, is not hereditary.
- Type 1 VWD is found in 60%-80% of patients. People with type 1 VWD have a low levels of VWF in their blood. Levels of VWF in the blood range from 20%-50% of normal. The symptoms are usually mild. There is one subtype called Type 1C where the VWF has increased clearance leading to prolonged bleeding.
- Type 2 VWD is found in 15%-30% of patients. People with type 2 VWD have a normal levels of VWF, but the factor doesn’t function as it should. Type 2 is broken down into four subtypes: type 2A, type 2B, type 2M and type 2N, depending on the specific way the VWF is defective. Symptoms are mild to moderate.
- Type 3 VWD is found in 5%-10% of patients. People with type 3 VWD have a very low levels or no VWF in their blood.. Some people with this type of VWD may also be low in factor VIII (factor eight). Symptoms are typically severe, and include spontaneous bleeding episodes, often into their joints and muscles.
- Acquired VWD. This type of VWD in adults results after a diagnosis of an autoimmune disease, such as lupus, or from heart disease or some types of cancer. It can also occur after taking certain medications.
How is VWD diagnosed?
A combination of blood tests are used to diagnose VWD, including a VWF antigen test, which measures the amount of VWF in the blood, tests that measure clotting time and ability to form a clot, and tests measuring platelet function. Some of these tests may have to be repeated, because the levels of VWF can change due to stress, exercise, the use of birth control pills, pregnancy, and hyperthyroidism. People with VWD usually have less than 50% of normal VWF in their blood. After a diagnosis of VWD is discovered, an additional is given to determine the type. The best place for patients with bleeding disorders to be diagnosed and treated is at one of the federally funded hemophilia treatment centers (HTCs) that are spread throughout the country. HTCs provide comprehensive care from skilled hematologists and other professional staff, including nurses, physical therapists, social workers and sometimes dentists, dieticians and other healthcare providers. In addition, HTCs often have specialized labs that can run more accurate VWD testing.
What are different types of treatment?
Treatment for VWD depends on the diagnosis and severity. Some bleeds are mild enough not to require treatment at all.
Other rare factor-deficient bleeding disorders
In the US, a rare disease or disorder is defined as one that affects fewer than 200,000 people. This means hemophilia A and B, and the less-common factor deficiencies such as I, II, V, VII, X, XI, XII and XIII, are all rare disorders.
Blood clotting is a complex process, involving many different proteins, called factors, each of which plays a different role in the blood clotting process. Factor deficiencies are defined by which specific clotting protein in the blood protein is low, missing or doesn’t work properly.
How Many People Have Rare Factor Deficiencies?
Factor I (1) Deficiency
Factor I deficiency is a collective term for three rare inherited fibrinogen deficiencies. One of these, afibrinogenemia is very rare, occurring in 1-2 people per million.
Factor II (2) Deficiency
Factor II deficiency is estimated to occur in 1 out of every 2 million people.
Factor V (5) Deficiency
Factor V deficiency is estimated to occur in 1 out of every 2 million people.
Factor VII (7) Deficiency
Factor VII deficiency is estimated to occur in 1 out of every 300,000-500,000 people. That makes it the most common of the rare factor deficiencies.
Factor X (10) Deficiency
Factor X deficiency is estimated to occur in 1 in 500,000 to 1 in a million people.
Factor XI (11) Deficiency (Hemophilia C)
Factor XI deficiency is estimated to occur in 1 in 100,000 people.
Factor XII (12)
Factor XII deficiency is estimated to occur in 1 in a million people.
Factor XIII (13) Deficiency
Factor XIII deficiency is estimated to occur in 1 in 5 million people. It is the rarest of the rare factor deficiencies.
What are different types of treatment?
How rare factor deficiencies are treated depends on the missing protein. Some can be treated with factor concentrates that replace the missing clotting factor. Others are treated with fresh frozen plasma, which is the liquid part of whole blood, or antifibrinolytics, which slow the breakdown of blood clots. Some do not require treatment at all.