Scenario 5 (English)
Tutorial 7th Block versi I
Author : Didit
Hemophilia is an inherited bleeding disorder in which the
blood does not clot properly. Blood contains many proteins called clotting
factors that help to stop bleeding. These factors are numbered from 1 through
13, using roman numerals (such as I, IV, or X). People with hemophilia have
either a low level of these clotting factors or none at all. The lower the
level, the more serious the hemophilia, and problems such as bleeding without
obvious cause or bleeding following injuries or surgery is more likely.
Hemophilia can result in:
- Joint swelling that can lead to damage or swelling in the muscle
- Bleeding in the head and sometimes in the brain leading to brain damage
- Damage to other organs in the body
- Pain as a result of bleeding in various organs
- Death can occur if the bleeding cannot be stopped or if it occurs in a vital organ such as the brain.
Types
There
are several different types of hemophilia. The following two are the most
common:
- Hemophilia A (Classic Hemophilia)
This type is caused by a lack or decrease of clotting factor
VIII (8).
- Hemophilia B (Christmas Disease)
This type is caused by a lack or decrease of clotting factor
IX (9).
Signs and Symptoms
The major signs of hemophilia are
bleeding that is unusually heavy or lasts a long time, or bleeding and bruising
that happens without obvious cause. The amount of bleeding depends on the type
and severity of hemophilia and how serious it is.
Other common signs include:
- Bleeding into the joints. This can cause swelling and pain or tightness in the joints; it often affects the knees, elbows, and ankles.
- Bleeding into the skin (which is bruising) or muscle and soft tissue causing a build-up of blood in the area (called a hematoma).
- Bleeding of the mouth and gums, and bleeding that is hard to stop after losing a tooth.
- Bleeding after circumcision (surgery performed on male babies to remove the hood of skin, called the foreskin, covering the head of the penis).
- Bleeding after having shots.
- Bleeding in the head of an infant after a difficult delivery.
- Blood in the urine or stool.
- Frequent and hard-to-stop nosebleeds.
Causes
Hemophilia is caused by a problem in one of the genes that tells the body to make the clotting factor proteins needed to form a blood clot. These genes are located on the X chromosome. All males have one X and one Y chromosome (XY) and all females have two X chromosomes (XX).
Males who inherit an affected X chromosome have hemophilia. Rarely, a condition called "female hemophilia" occurs. In such cases both X chromosomes are affected or one is missing or inactive. In these women, bleeding symptoms may be similar to males with hemophilia.
A female who inherits one affected X chromosome becomes a "carrier" of hemophilia. A female who is a carrier sometimes can have symptoms of hemophilia. In addition, she can pass the affected gene on to her children. Learn more about the inheritance pattern for hemophilia.
Even though hemophilia is genetic, it does occur among families with no prior history. About one-third of newly diagnosed babies have no family history of hemophilia. These cases are thought to be due to a change to the gene's instructions for making the clotting factor protein, called a "mutation." This change or mutation can prevent the clotting protein from working properly or to be missing altogether.
The following examples show how the
hemophilia gene can be inherited. It is important to note that in
one-third of people with hemophilia, there is no family history of the
disorder.
- In this example, the mother is a carrier of the hemophilia gene, and the father does not have hemophilia.
- There is a 50% chance that each son will have hemophilia.
- There is a 50% chance that each daughter will be a carrier of the hemophilia gene.
2. In this example, the father has
hemophilia, and the mother does not carry the hemophilia gene.
- All daughters will carry the hemophilia gene.
- No sons will have hemophilia.
3. In this example, the father does not
have hemophilia, and the mother does not carry the hemophilia gene.
- None of the children (daughters or sons) will have hemophilia or carry the gene.
Who is Affected
Hemophilia is a common inherited bleeding disorder. Hemophilia occurs among about 1 of every 5,000 male births. Currently, about 20,000 males in the United States have the disorder. Hemophilia A is about four times as common as hemophilia B, and about half of those affected have the severe form. Hemophilia affects people from all racial and ethnic groups.
Diagnosis
Many people who have or have had family members with hemophilia will ask that their baby boys get tested soon after birth.
About one-third of babies who are diagnosed with hemophilia have no other family members with the disorder. A doctor might check for hemophilia if a newborn is showing certain signs of hemophilia.
Diagnosis includes screening tests and clotting factor tests. Screening tests are blood tests that show if the blood is clotting properly. Clotting factor tests, also called factor assays, are required to diagnose a bleeding disorder. This blood test shows the type of hemophilia and the severity.
Families With a History of Hemophilia
Any family history of bleeding, such as following surgery or injury, or unexplained deaths among brothers, sisters, or other male relatives such as maternal uncles, grandfathers, or cousins should be discussed with a doctor to see if hemophilia was a cause. A doctor often will get a thorough family history to find out if a bleeding disorder exists in the family.
Many people who have or have had family members with hemophilia will ask that their baby boys get tested soon after birth. In the best of cases, testing for hemophilia is planned before the baby’s delivery so that a sample of blood can be drawn from the umbilical cord (which connects the mother and baby before birth) immediately after birth and tested to determine the level of the clotting factors. Umbilical cord blood testing is better at finding low levels of factor VIII (8) than it is at finding low levels of factor IX (9). This is because factor IX (9) levels take more time to develop and are not at a normal level until a baby is at least 6 months of age. Therefore, a mildly low level of factor IX (9) at birth does not necessarily mean that the baby has hemophilia B. A repeat test when the baby is older might be needed in some cases. Learn more about the inheritance pattern for hemophilia.
Families With No Previous History of Hemophilia
About one-third of babies who are diagnosed with hemophilia have no other family members with the disorder. A doctor might check for hemophilia in a newborn if:
- Bleeding after circumcision of the penis goes on for a long time.
- Bleeding goes on for a long time after drawing blood and heel sticks (pricking the infant’s heel to draw blood for newborn screening tests).
- Bleeding in the head (scalp or brain) after a difficult delivery or after using special devices or instruments to help deliver the baby (e.g., vacuum or forceps).
- Unusual raised bruises or large numbers of bruises. If a child is not diagnosed with hemophilia during the newborn period, the family might notice unusual bruising once the child begins standing or crawling.
Those with
severe hemophilia can have serious bleeding problems right away. Thus, they
often are diagnosed during the first year of life. People with milder forms of
hemophilia might not be diagnosed until later in life.
Screening Tests
Screening tests are blood tests that show if the blood is clotting properly. Types of screening tests:
Complete Blood Count (CBC)
This common test measures the amount of hemoglobin (the red pigment inside red blood cells that carries oxygen), the size and number of red blood cells and numbers of different types of white blood cells and platelets found in blood. The CBC is normal in people with hemophilia. However, if a person with hemophilia has unusually heavy bleeding or bleeds for a long time, the hemoglobin and the red blood cell count can be low.
Activated
Partial Thromboplastin Time (APTT) Test
This test
measures how long it takes for blood to clot. It measures the clotting ability
of factors VIII (8), IX (9), XI (11), and XII (12). If any of these clotting
factors are too low, it takes longer than normal for the blood to clot. The
results of this test will show a longer clotting time among people with
hemophilia A or B.
Prothrombin Time (PT) Test
This test also
measures the time it takes for blood to clot. It measures primarily the
clotting ability of factors I (1), II (2), V (5), VII (7), and X (10). If any
of these factors are too low, it takes longer than normal for the blood to
clot. The results of this test will be normal among most people with hemophilia
A and B.
Fibrinogen Test
This test also
helps doctors assess a patient’s ability to form a blood clot. This test is
ordered either along with other blood clotting tests or when a patient has an
abnormal PT
or APTT test
result, or both. Fibrinogen is another name for clotting factor I (1).
Clotting Factor Tests
Clotting factor
tests, also called factor assays, are required to diagnose a bleeding disorder.
This blood test shows the type of hemophilia and the severity. It is
important to know the type and severity in order to create the best treatment
plan.
|
Severity
|
Levels of Factor VIII (8)
or IX (9) in the blood |
|
Normal (person who does not have hemophilia)
|
50% to 100%
|
|
Mild hemophilia
|
Greater than 5% but less than 50%
|
|
Moderate hemophilia
|
1% to 5%
|
|
Severe hemophilia
|
Less than 1%
|
Treatment
The best way to
treat hemophilia is to replace the missing blood clotting factor so that the
blood can clot properly. This is done by injecting commercially prepared
clotting factor concentrates into a person’s vein.
Hemophilia is a
complex disorder. Good quality medical care from doctors and nurses who know a
lot about the disorder can help prevent some serious problems. Often the best
choice is a comprehensive Hemophilia Treatment Center (HTC). An HTC
provides care to address all issues related to the disorder, as well as
education.
Treatment Centers
Hemophilia is a
complex disorder. Good quality medical care from doctors and nurses who know a
lot about the disorder can help prevent some serious problems. Often the best
choice is a comprehensive hemophilia treatment center (HTC). An HTC
provides care to address all issues related to the disorder, as well as
education. The team consists of physicians (hematologists or blood
specialists), nurses, social workers, physical therapists and other health care
providers, who are specialized in the care of people with bleeding disorders.
Blood Clotting Factor
The best way to
treat hemophilia is to replace the missing blood clotting factor so that the
blood can clot properly. This is done by injecting commercially prepared
clotting factor concentrates into a person’s vein.
The two main types of clotting
factor concentrates available are:
Plasma-Derived
Factor Concentrates
Plasma is the
liquid part of blood. It is pale yellow or straw colored and contains proteins
such as antibodies, albumin and clotting factors. Several factor
concentrates that are made from human plasma proteins are available. All blood
and parts of blood, such as plasma, are routinely tested for the viruses. The
clotting proteins are separated from other parts of the plasma, purified, and
made into a freeze-dried product. This product is tested and treated to kill
any potential viruses before it is packaged for use.
Recombinant Factor Concentrates
Until 1992, all
factor replacement products were made from human plasma. In 1992, the U.S. Food
and Drug Administration (FDA) approved recombinant factor VIII (8) concentrate,
which does not come from human plasma. The concentrate is genetically
engineered using DNA technology. Commercially prepared factor concentrates are
treated to remove or inactivate bloodborne viruses. In addition, recombinant
factors VIII (8) and IX (9) are available that do not contain any plasma or
albumin and, therefore, cannot transmit any bloodborne viruses.
The products
can be used as needed when a person is bleeding or they can be used on a
regular basis to prevent bleeds from occurring. Today, people with hemophilia
and their families can learn how to give their own clotting factor at home.
Giving factor at home means that bleeds can be treated quicker, resulting in
less serious bleeding and fewer side effects.
Other treatment products:
DDAVP® (Desmopressin Acetate)
DDAVP® is a
chemical that is similar to a hormone that occurs naturally in the body. It
releases factor VIII (8) from where it is stored in the body tissues. For people
with mild, and some cases of moderate hemophilia, this can work to increase
their own factor VIII (8) levels so that they do not have to use clotting
factor. This medicine can be given through a vein (DDAVP®) or through nasal
spray (Stimate®).
Amicar® (Epsilon Amino Caproic Acid)
Amicar® is a
chemical that can be given in a vein or by mouth (as a pill or a liquid). It
prevents clots from breaking down, resulting in a firmer clot. It is often used
for bleeding in the mouth or after a tooth has been removed because it blocks
an enzyme in the saliva that breaks down clots.
Cryoprecipitate
Cryoprecipitate
is a substance that comes from thawing fresh frozen plasma. It is
rich in factor VIII (8) and was commonly used to control serious bleeding
in the past. However, because there is no method to kill viruses, such as
HIV and hepatitis, in cryoprecipitate it is no longer used as the current
standard of treatment in the U.S. It is, however, still used in most
developing countries.
Inhibitors
About 10 – 15
percent of people with hemophilia develop an antibody (called an inhibitor)
that inhibits the action of the clotting factors used to treat bleeding.
Treatment of bleeding becomes extremely difficult, and the cost of their care
can skyrocket because more clotting factor or a different type of clotting
factor is needed. Patients with inhibitors often experience increased joint
disease and other complications from bleeding that result in a reduced quality
of life.
Inhibitors
People with
hemophilia have a higher quality of life today than ever before, but
complications can still occur. As many as one third of people with hemophilia
will develop an antibody—called an inhibitor—to the product used to treat or
prevent bleeding episodes. Developing an inhibitor is one of the most serious
and costly complications of hemophilia.
About Inhibitors
People with hemophilia use treatment products called factor
clotting concentrates. This treatment improves blood clotting and is used
to stop or prevent a bleeding episode. Inhibitors develop when the body’s
immune system stops accepting the factor (factor VIII for hemophilia A and
factor IX for hemophilia B) as a normal part of blood. The body thinks the
factor is a foreign substance and tries to destroy it using inhibitors. The
inhibitors stop the factor from working. This makes it more difficult to stop a
bleeding episode. People with hemophilia who develop an inhibitor do not
respond as well to treatment. Inhibitors most often appear during the first
year of treatment but they can appear at any time.
Cost of Care
Caring for people with inhibitors poses a special challenge.
The health care costs associated with inhibitors can be staggering because of
the cost and amount of treatment product required to stop bleeding. Also,
people with hemophilia who develop an inhibitor are twice as likely to be
hospitalized for a bleeding complication.
Risk Factors and
Causes
Scientists do not know exactly what causes inhibitors. Risk
factors that have been shown in some studies to possibly play a role include:
- Age
- Race/ethnicity
- Type of hemophilia gene defect
- Frequency and amount of treatment (inhibitors typically occur within the first 50 times factor is used)
- Family history of inhibitors
- Type of factor treatment product
- Presence of other immune disorders
Diagnosis
A blood test is used to diagnose inhibitors. The blood test
measures inhibitor levels (called inhibitor titers) in the blood. The amount of
inhibitor titers is measured in Bethesda units (BU). The higher the number of
Bethesda units, the more inhibitor is present. “Low titer” inhibitor has a very
low measurement, usually less than 5 BU. “High titer” inhibitor has a very high
measurement, usually much higher than 5 BU.
Inhibitors are also labeled “low responding” or “high
responding” based on how strongly a person’s immune system reacts or responds
to repeated exposure to factor concentrate. When people with
high-responding inhibitors receive factor concentrates, the inhibitor titer
measurement increases quickly. The increased inhibitor titer prevents the
factor clotting concentrates from stopping or preventing a bleeding episode.
Repeated exposure to factor clotting concentrates will cause more inhibitors to
develop.
When people with low-responding inhibitors receive factor
concentrates, the inhibitor titers do not rise. Therefore, people with
low-responding inhibitors can usually still use factor clotting concentrates to
stop or prevent a bleeding episode.
Treatment
Treating people who have inhibitors is complex and remains
one of the biggest challenges in hemophilia care today. If possible, a person
with inhibitors should be cared for at a hemophilia treatment center (HTC).
HTCs are specialized health care centers that bring together a team of doctors,
nurses, and other health professionals experienced in treating people with
hemophilia.
Some
treatments for people with inhibitors include the following:
- High-Dose Clotting Factor Concentrates: People who have low responding inhibitors may be treated with higher amounts of factor concentrate to overcome the inhibitor and yet have enough left over to form a clot. It is important to test the blood and measure the factor level after this new treatment schedule is established to see if the inhibitor is gone.
- Bypassing Agents: Special blood products are used to treat bleeding in people with high titer inhibitors. They are called bypassing agents. Instead of replacing the missing factor, they go around (or bypass) the factors that are blocked by the inhibitor to help the body form a normal clot. People taking bypassing agents should be monitored closely to make sure the blood is not clotting too much or clotting in the wrong place in the body.
- Immune Tolerance Induction (ITI) Therapy: The goal of ITI therapy is to stop the inhibitor reaction from happening in the blood and to teach the body to accept clotting factor concentrate treatments. With ITI therapy, people receive large amounts of clotting factor concentrates every day for many weeks or months.
ITI therapy requires specialized medical expertise, is
costly, and may take a long time to work. In many cases, ITI gets rid of the
inhibitor. However, patients may need to continue taking frequent, large
amounts of factor concentrates for many years to keep the inhibitor from coming
back. HTCs
can serve a vital role in supporting patients who undergo a treatment regimen
as intensive as ITI.
Author : Didit
Source : http://www.cdc.gov/NCBDDD/hemophilia/inhibitors.html
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