Hemophilia is a rare inherited bleeding disorder in which the blood does not clot normally. Persons with hemophilia may bleed for a longer time
than others after an injury or accident. They also may bleed internally,
especially in the joints (e.g., knees,
ankles, and elbows).
Babies born with hemophilia are missing or have a low level of a protein needed for normal blood clotting or blood coagulation. The protein is called a clotting factor.
About 18,000 people in the United States have hemophilia. Each year, about
400 babies are born with the disorder. Hemophilia usually occurs only in
males (with very rare exceptions).
A person with hemophilia has a problem with certain proteins in the blood
called clotting factors. Hemophilia can be due to:
When clotting factors are missing, or your body does not have enough of
these factors, it can take a long time for your blood to clot after an injury
- A low level of one of the clotting factors
- A clotting factor that is completely missing
What is clotting?
An injury (like a cut) to a blood vessel causes a complex chain of events
that results in a blood clot. This clotting process is also called blood
coagulation. Clotting is your body's reaction to bleeding and keeps you
from losing too much blood. Losing too much blood can be life threatening
and can damage your internal organs.
What is a clotting
Clotting factors are proteins in the blood that work with platelets – a type of small blood cell – to help the blood to clot. When
blood vessels are damaged, clotting factors help the platelets stick together
to plug cuts and breaks at the site of the injury.
In people with hemophilia, blood does not clot as it should because it is
missing or has low levels of one of these clotting factors. If blood doesn't
clot as quickly or as well as it should, then:
Sometimes people with hemophilia need infusions of a clotting factor or
factors to stop bleeding.
- Heavy blood loss can occur.
- Body organs and tissues can be injured.
- These conditions can result in permanent damage or death.
Types of hemophilia
The two main types of hemophilia are:
Hemophilia also can be acquired when antibodies to these clotting factors form and block their function. Only inherited
hemophilia is discussed here.
- Hemophilia A: Clotting factor
VIII (8) is low or missing. About 9 of 10 people with hemophilia
have type A.
- Hemophilia B: Clotting factor IX (9) is low or missing.
Hemophilia can be:
Mild, moderate, or severe hemophilia is determined by the amount of clotting
factor in the blood. About 7 of 10 people with hemophilia A have the severe
form. Normal persons have a factor VIII activity of 100 percent; persons
with severe hemophilia A have a factor VIII activity of less than 1 percent.
What causes hemophilia?
Hemophilia is an inherited disorder. It is caused by a defect in the genes that determine how the body makes blood clotting factors VIII and IX. These
genes are located on the X chromosomes,
which determine whether a baby is a boy or girl.
Chromosomes come in pairs. Females have two X chromosomes, while males have
one X and one Y chromosome. A woman is a "carrier" if she has a defective
gene for factor VIII or factor IX on one of her X chromosomes. She can pass
the defective gene on to her children.
- If she has a son, there is a one in two (50 percent) chance that he
will have hemophilia.
- If she has a daughter, there is a one in two (50 percent) chance that
the daughter will be a carrier.
A man who has hemophilia cannot pass the disorder on to his sons. All of
his daughters, however, will be carriers.
Very rarely, a girl is born with hemophilia. This can happen if her father
has hemophilia and her mother is a carrier.
Some males with the disorder are born to mothers who are not carriers. In
these cases, a random change (mutation) occurs in the gene as it is passed
to the child.
Signs and symptoms of hemophilia
The major signs and symptoms of hemophilia are bleeding and bruising. Internal
bleeding is common in people with severe hemophilia. If not treated promptly,
internal bleeding can lead to damaged joints, muscles, or other parts of
The extent of bleeding depends on the type and severity of the condition:
In most children, the first signs are:
- Children with very mild hemophilia may not have noticeable symptoms
for years. Often, the first sign is heavy bleeding from a dental procedure,
an accident, or surgery.
- Children with mild to moderate hemophilia may not have any signs or
symptoms at birth.
- Males with severe hemophilia may bleed heavily after circumcision.
Females who are carriers usually have enough clotting factors from their
one normal gene to prevent serious bleeding problems.
- Heavy bruising and bleeding from the gums as they cut their baby teeth
- Bumps and bruises from frequent falls as they learn to walk
- Swelling and bruising from bleeding in the joints, soft tissue, and
The most common signs or symptoms in older children and adults are:
Bleeding in the joints is the most common problem in persons with severe
hemophilia. Bleeding often occurs without an injury. It can go on for days
if not treated. However, people with hemophilia can learn to recognize early
symptoms of bleeding in the joints and get treatment quickly. Early treatment
can help limit damage to the joints.
- Bleeding in the joints (hemarthrosis)
- Bleeding and bruising in the soft tissue and muscles
- Bleeding in the mouth from a cut or bite or loss of a tooth
- Nosebleeds for no obvious reason
- Blood in the urine (from bleeding in
the kidneys or bladder)
- Blood in the stool (from bleeding in the intestines or stomach)
Although bleeding can occur in any joint, the most common places are the:
The signs and symptoms of bleeding in the joints are:
If not treated, the bleeding can lead to disabling arthritis in the joints.
- Tightness in the joint with no real pain is usually the first sign.
- Tightness and pain may occur before any visible signs of bleeding.
- The joint becomes swollen and hot to touch as time passes. Bending
or extending the joint is painful.
- Swelling continues as bleeding continues, and all movement in the
joint is lost. Pain can be severe.
The bleeding slows after several days when the joint is full of blood.
Bleeding in the brain, a very serious complication of hemophilia, requires
emergency treatment. This bleeding can happen after a simple bump on the
head or a more serious injury. The signs and symptoms are:
- Long-lasting painful headaches
- Vomiting many times
- Changes in behavior or being very sleepy
- Sudden weakness or clumsiness of the arm or leg
- Neck pain or stiffness
- Double vision
- Difficulty walking
- Convulsions or seizures
If hemophilia is suspected or if you appear to have a bleeding problem,
your doctor will take a personal and family history, do a physical exam,
and order blood tests.
Blood tests are used to determine:
The test results will show if you have hemophilia, what type of hemophilia
you have, and how severe it is.
- How long it takes for your blood to clot
- Whether your blood has low levels of any of the clotting factors
- Whether one of the factors is completely missing from your blood
Hemophilia A and B are classified as mild, moderate, or severe, depending
on the amount of clotting factor VIII (8) or IX (9) in the blood.
Mild hemophilia: >5–30 percent of normal factor
Moderate hemophilia: 1–5 percent of normal factor
Severe hemophilia: Less than 1 percent of normal factor
Severe hemophilia can cause serious bleeding problems in babies. Therefore,
children with severe hemophilia are usually diagnosed during the first year
of life. People with milder forms of hemophilia may not be diagnosed until
they are adults.
The bleeding problems of hemophilia A and hemophilia B are the same. These
two types of hemophilia can only be distinguished by special blood tests.
Distinguishing hemophilia A from hemophilia B is important because the treatments
The main treatment for hemophilia is replacement therapy – giving
or replacing the clotting factor that is too low or missing. Concentrates
of the clotting factor are infused, or injected, directly into the bloodstream.
The specific factors used to treat hemophilia are:
Replacement therapy can be used:
- Factor VIII for hemophilia A
- Factor IX for hemophilia B
The type of treatment you receive depends on several things, including whether
you have mild, moderate, or severe hemophilia.
- To prevent bleeding (prophylactic or preventive therapy)
- To stop bleeding when it occurs, on an as-needed basis (demand therapy)
- Mild hemophilia. Replacement therapy is usually not needed
for mild hemophilia; however, a medicine called desmopressin (DDAVP)
is sometimes given to raise the body's levels of factor VIII. Since
the effect wears off with chronic use, it is applied only in certain
situations (for example, prior to dental work or participation in sports)
to prevent or reduce bleeding. Desmopressin does not help in hemophilia
- Moderate hemophilia. You may need treatment only when bleeding
occurs. You will need to learn to recognize signs and symptoms of bleeding
so that you can get treatment as quickly as possible. You may also have
treatment to prevent bleeding that could occur when participating in
- Severe hemophilia. You usually need long-term or shorter term
preventive therapy to prevent bleeding that could cause permanent damage
to your joints, muscles, or other parts of the body. Some people with
severe hemophilia receive treatment only when bleeding occurs, however.
When bleeding occurs, it is important to get treatment as soon as possible.
Delayed treatment can lead to complications. Learn to recognize signs
of bleeding, and make sure that it is treated quickly.
Sources of clotting factors
The clotting factor concentrates used in replacement therapy come from two
Clotting factor concentrate infusions need to be given once daily or more
frequently when treatment is started, because half of the activity of factor
VIII is gone in 8–12 hours and half of the activity of factor IX is gone
in 12–24 hours.
- Blood from human donors
- Lab-produced clotting factors, called recombinant factors, that are
not made from human blood
Clotting factors used in replacement therapy today are:
- Very powerful – only a small amount is needed to control bleeding.
- Easy to store, mix, and use at home – it takes only about 15
minutes to receive the factor.
Replacement therapy to prevent bleeding
Replacement therapy can be given on a regular basis to prevent bleeding.
The goal is to keep the levels of clotting factors in the blood high enough
that bleeding will not occur.
This therapy is more likely to be used in persons with severe hemophilia.
It is often used in children to prevent damage to joints from bleeding.
Preventive replacement therapy can be given:
This therapy can be intensive and expensive. Preventive therapy is often
given at home.
- On a long-term basis, usually given two or three times a week
- On a shorter term basis, such as over a few months
- On a short-term basis before participating in an activity that could
Replacement therapy to stop bleeding when
Replacement therapy can be given as needed, or on demand, to stop bleeding
as soon as possible after it begins. The goal is to prevent damage to joints,
muscles, or other parts of the body from bleeding. This therapy is common
for people with mild or moderate hemophilia.
The amount of clotting factor given depends on:
Therapy that is given as needed is less intensive and less expensive than
regular preventive therapy. However, there is a risk that bleeding will
cause damage before the treatment is given.
- The type of hemophilia
- The bleeding site and severity of the bleeding
- The person's weight
- Whether the person has developed an antibody that neutralizes or knocks
out the activity of the clotting factor
People who use this form of treatment must learn to recognize bleeding when
it occurs. Treatment must begin right away to limit damage. Family members
should also learn to watch for signs of bleeding in a child. Children sometimes
ignore signs of bleeding because they want to avoid the discomfort of treatment.
Complications of replacement therapy
Complications of treatment include:
- Developing antibodies, which are proteins that knock out the activity
of clotting factors
- Damage to joints, muscles, or other parts of the body, resulting from
delays in treatment
Antibodies to the clotting factor
Antibodies destroy the clotting factor before it has a chance to work. This
is a very serious problem, because the main treatment for hemophilia –
replacing clotting factors – is no longer effective.
Antibodies to clotting factor develop in about:
When antibodies develop, doctors may use larger doses of clotting factors
or try different sources of the clotting factor. Sometimes, antibodies go
away. Researchers are studying ways to deal with antibodies to clotting
- Twenty percent of people with severe hemophilia A
- One percent of people with hemophilia B
Viruses from human blood factors
The viruses that cause AIDS (HIV) and hepatitis can be carried in
clotting factors. However, no documented case of transmission of these viruses
has occurred for about a decade. Transmission of viruses has been prevented
Researchers continue to find ways to make blood products safer.
- Careful screening of donors
- Testing of donated blood products
- Treating donated blood products, used to create clotting factors,
with a detergent and heat to destroy viruses
Damage due to delays in treatment
When treatment for bleeding is delayed, damage to the area affected (such
as a joint) can occur. It is important for persons with hemophilia to learn
to recognize signs of bleeding as soon as possible after bleeding starts
and to get treatment quickly.
Both preventive and as-needed therapy can be done at home. Many people learn
to do the infusions at home for their child or for themselves. Home treatment
has several advantages:
Discuss options for home treatment with your doctor or your child's doctor.
A doctor or other health care provider can teach you the steps and safety
procedures for home treatment. Another valuable resource for learning about
home treatment is through hemophilia treatment centers (HTCs) (see below).
- You or your child can get treatment quicker when bleeding happens.
Early treatment means that fewer complications are likely to occur.
- Fewer visits to the doctor or emergency room are needed.
- Home infusions cost less than treatment in a medical care setting.
- Home treatment helps children accept treatment and take responsibility
for their own health.
Vein access devices can be surgically implanted to make it easier to access
a vein to do the infusions. These devices can be helpful when infusions
are done on a frequent basis. However, infections can be a problem with
these devices. Your doctor can help you decide if this type of device is
right for you or your child.
Hemophilia treatment centers
A nationwide network of HTCs, funded by the Federal Government, is an important
resource for families and individuals affected by hemophilia. The medical
experts in these centers provide treatment, education, and support. They
can teach you or your child how to do home infusions safely. Center staff
can also provide information to your doctor.
People who get care in these centers are less likely than those who get
care elsewhere to have bleeding complications. This lack of complications
may be due to the centers' emphasis on prevention of bleeding and the education
and support provided to patients and their caregivers.
- Desmopressin (DDAVP) is a synthetic hormone used to treat people
with mild to moderate hemophilia A. DDAVP cannot be used to treat hemophilia
B or severe hemophilia A. DDAVP stimulates the release of factor VIII
and von Willebrand factor stored in blood vessels and increases the
level of these proteins in the blood. Von Willebrand factor carries
and binds factor VIII, which then can stay in the blood circulation
longer. DDAVP usually is given by injection or in a nasal spray.
- Antifibrinolytic drugs (including tranexamic acid and aminocaproic
acid) are medicines used with factor treatment. They are usually given
as a pill to help keep clots from breaking down. They are most often
- Before dental work
- For treating bleeding from the mouth or nose
- For mild intestinal bleeding
Source: National Human Genome Research