CONTENTS

1. WHAT IS HAEMOPHILIA? 1

2. CAUSES FOR HAEMOPHILIA 3

3. TYPES OF HAEMOPHILIA 5

4. HOW IS HAEMOPHILIA INHERITED ? 7

5. SYMPTOMS OF HAEMOPHILIA 9

6. DIAGNOSIS OF HAEMOPHILIA 10

7. TREATMENT FOR HAEMOPHILIA 14

8. PEDIGREE CHARTS 16

9. BIBLIOGRAPHY 18
WHAT IS HEMOPHILIA ?

Hemophilia is usually an inherited bleeding disorder in which the blood does not
clot properly. This can lead to spontaneous bleeding as well as bleeding following
injuries or surgery. Blood contains many proteins called clotting factors that can
help to stop bleeding. People with haemophilia have low levels of either factor
VIII (8) or factor IX (9). The severity of haemophilia that a person has is
determined by the amount of factor in the blood. The lower the amount of the
factor, the more likely it is that bleeding will occur which can lead to serious
health problems.
In rare cases, a person can develop haemophilia later in life. The majority of
cases involve middle-aged or elderly people, or young women who have recently
given birth or are in the later stages of pregnancy. This condition often resolves
with appropriate treatment.
CAUSES FOR HEMOPHILIA

Hemophilia is caused by a mutation or change, in one of the genes, that provides

instructions for making the clotting factor proteins needed to form a blood clot.
This change or mutation can prevent the clotting protein from working properly
or to be missing altogether. These genes are located on the X chromosome. Males
have one X and one Y chromosome (XY) and females have two X chromosomes
(XX). Males inherit the X chromosome from their mothers and the Y
chromosome from their fathers. Females inherit one X chromosome from each
parent.

The X chromosome contains many genes that are not present on the Y
chromosome. This means that males only have one copy of most of the genes on
the X chromosome, whereas females have 2 copies. Thus, males can have a
disease like haemophilia if they inherit an affected X chromosome that has a
mutation in either the factor VIII or factor IX gene. Females can also have
haemophilia, but this is much rarer. In such cases both X chromosomes are
affected or one is affected and the other is missing or inactive. In these females,
bleeding symptoms may be similar to males with haemophilia.

A female with one affected X chromosome is a “carrier” of haemophilia.

Sometimes a female who is a carrier can have symptoms of haemophilia. In
addition, she can pass the affected X chromosome with the clotting factor gene
mutation on to her children.

Even though haemophilia runs in families, some families have no prior history of
family members with haemophilia. Sometimes, there are carrier females in the
family, but no affected boys, just by chance. However, about one-third of the
time, the baby with haemophilia is the first one in the family to be affected with a
mutation in the gene for the clotting factor.

Hemophilia can result in:

•Bleeding within joints that can lead to chronic joint disease and pain
•Bleeding in the head and sometimes in the brain which can cause long
term problems, such as seizures and paralysis
•Death can occur if the bleeding cannot be stopped or if it occurs in a vital
organ such as the brain.
TYPES OF HAEMOPHILIA

There are several different types of haemophilia. The following two are the most
common:

Hemophilia A (Classic Hemophilia) .This type is caused by a lack or

decrease of clotting factor VIII
Hemophilia A, also known as classical hemophilia, is a genetic bleeding disorder
caused by insufficient levels of a blood protein called factor VIII. Factor VIII is a
clotting factor. Clotting factors are specialized proteins that are essential for
proper clotting, the process by which blood clumps together to plug the site of a
wound to stop bleeding. Individuals with hemophilia A do not bleed faster or
more profusely than healthy individuals, but because their blood clots poorly, they
have difficulty stopping the flow of blood from a wound. This may be referred to
as prolonged bleeding or a prolonged bleeding episode. Hemophilia A can be
mild, moderate or severe, depending on the baseline level of factor VIII made by
that individual. In mild cases, prolonged bleeding episodes may only occur after
surgery, dental procedures or trauma. In more severely affected individuals,
symptoms may include prolonged bleeding from minor wounds, painful swollen
bruises, and unexplained (spontaneous) bleeding into vital organs as well as joints
and muscles (internal bleeding).

Hemophilia B (Christmas Disease) .This type is caused by a lack or decrease of

clotting factor IX.

Hemophilia B is a rare genetic bleeding disorder in which affected individuals

have insufficient levels of a blood protein called factor IX. Factor IX is a clotting
factor. Clotting factors are specialized proteins needed for blood clotting, the
process by which blood seals a wound to stop bleeding and promote healing.
Individuals with hemophilia B do not bleed faster than unaffected individuals,
they bleed longer. This is because they are missing or have a decreased amount of
a protein involved in blood clotting and are unable to effectively stop the flow of
blood from a wound, injury or bleeding site. This is sometimes referred to as
prolonged bleeding or a bleeding episode.
Hemophilia B is classified as mild, moderate or severe based upon the activity
level of factor IX. In mild cases, bleeding symptoms may occur only after
surgery, injury or a dental procedure. In some moderate and most severe cases,
bleeding symptoms may occur after a minor injury or spontaneously, meaning
without an identifiable cause.
Hemophilia B is caused by changes (variants or mutations) in the factor IX gene
(F9) on the X chromosome. Hemophilia B is most commonly identified in males;
however, females who carry the gene may have mild or, rarely, more severe
symptoms of bleeding and should have their factor IX level checked.
HOW IS HEMOPHILIA INHERITED??

Hemophilia is a bleeding disorder in which blood does not clot properly. Blood
contains many proteins, called clotting factors, that can help to stop bleeding after
injury or surgery. People with haemophilia have low amounts of either factor VIII
(eight) or factor IX (nine), key factors responsible for normal blood clotting.
A person’s genes provide the instructions on how to make proteins, such as factor
VIII and factor IX. In people with haemophilia, there is a mutation (difference
from normal) in either the gene for the factor VIII protein or the gene for the
factor IX protein. The mutation causes the body to produce too little factor VIII or
IX. This change in a copy of the gene making factor VIII or factor IX is called a
haemophilia allele.
Most people who have haemophilia are born with it. It almost always is inherited
(passed down) from a parent to a child. Both haemophilia A and B are inherited
in the same way, because both the genes for factor VIII and factor IX are located
on the X chromosome (chromosomes are structures within the body’s cells that
contain the genes). The X and Y chromosomes determine whether a person’s sex
is male or female; females have two X chromosomes (XX) and males have one X
chromosome and one Y chromosome (XY). There are no genes for clotting
factors on the Y chromosome. This means that males only have one allele for
factor VIII and one allele for factor IX. Thus, if a male has a haemophilia allele
on his only X chromosome, he will have the disorder.
A female inherits two copies of the factor VIII or factor IX gene, one from her
mother and one from her father. A female with a haemophilia allele on one X
chromosome usually has a normal allele on her other X chromosome that can
produce normal clotting factor, so she has some protection against having
haemophilia. A female with one haemophilia allele and one normal allele is called
heterozygous or a carrier. Some girls and women who are heterozygous have
bleeding symptoms, but usually they are milder than those of boys and men with
haemophilia. In rare cases, a female who is heterozygous can have bleeding
symptoms that are just as serious as those of a male with haemophilia. A female
can also have haemophilia if she inherits haemophilia alleles from both of her
parents or if she inherits one haemophilia allele and her other X chromosomes is
missing or does not work properly. Hemophilia may be hidden in a family for
many generations if it passes only through females who do not have bleeding
symptoms.
If a mother is heterozygous (a carrier) for haemophilia and the father does not
have haemophilia, each son has a 1 in 2 (50%) chance of getting his mother’s
haemophilia allele and having haemophilia. Each daughter has a 1 in 2 (50%)
chance of getting her mother’s haemophilia allele and being heterozygous.
Overall, there is a 1 in 4 (25%) chance for each pregnancy that the baby will be a
son with haemophilia and a 1 in 4 (25%) chance that the baby will be a
heterozygous daughter. There is a 1 in 2 (50%) chance that the baby (either a son
or a daughter) will not get the haemophilia allele at all and, therefore, can’t pass it
down to his or her children.
SYMPTOMS OF HEMOPHILIA

Common signs of haemophilia 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 haematoma).
•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, such as vaccinations.
•Bleeding in the head of an infant after a difficult delivery.
•Blood in the urine or stool.
•Frequent and hard-to-stop nosebleeds.
DIAGNOSIS OF HEMOPHILIA

Many people who have or have had family members with haemophilia will ask
that their babies get tested soon after birth. About one-third of babies who are
diagnosed with haemophilia have a new mutation not present in other family
members. In these cases, a doctor might check for haemophilia if a newborn is
showing certain signs of haemophilia.
To make a diagnosis, doctors would perform certain blood tests to show if the
blood is clotting properly. If it does not, then they would do clotting factor tests,
also called factor assays, to diagnose the cause of the bleeding disorder. These
blood tests would show the type of haemophilia and the severity.

About one-third of babies who are diagnosed with haemophilia have no other
family members with the disorder. A doctor might check for haemophilia if a
newborn is showing certain signs of haemophilia.
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 haemophilia and the severity.
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 haemophilia was a cause. A doctor often will get a thorough family history to
find out if a bleeding disorder exists in the family.
Some babies should be tested for haemophilia soon after birth, including:
•Babies born to families with a history of haemophilia.
•Babies whose mothers are carriers of haemophilia.
•Babies who have bleeding symptoms at birth.
In the best of cases, testing for haemophilia 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 haemophilia B.
A repeat test when the baby is older might be needed in some cases.
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 haemoglobin (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 haemophilia. However, if a person with haemophilia has unusually
heavy bleeding or bleeds for a long time, the haemoglobin 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 is a protein in the blood that helps stop bleeding. Clotting factor
tests, also called factor assays, are required to diagnose a bleeding disorder. This
blood test shows the type of haemophilia and the severity. It is important to know
the type and severity in order to create the best treatment plan.
TREATMENT FOR HEMOPHILIA

The best way to treat haemophilia is to replace the missing blood clotting factor
so that the blood can clot properly. This is done by infusing (administering
through a vein) commercially prepared factor concentrates. People with
haemophilia can learn how to perform these infusions themselves so that they can
stop bleeding episodes and, by performing the infusions on a regular basis (called
prophylaxis), can even prevent most bleeding episodes.
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 for care is
to visit a comprehensive Hemophilia Treatment Center (HTC). An HTC not only
provides care to address all issues related to the disorder, but also provides health
education that helps people with haemophilia stay healthy.
Hemophilia is a complex disorder. Good quality medical care from doctors and
nurses who know a lot about the disorder can help people with haemophilia
prevent some serious problems. Often the best choice for care is at a
comprehensive haemophilia treatment Center (HTC). An HTC provides patients
with the care and education to address all issues related to the disorder. The team
consists of physicians (haematologists or blood specialists), nurses, social
workers, physical therapists, and other healthcare providers who are specialized in
the care of people with bleeding disorders.

Clotting Factor Products

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-coloured and contains
proteins such as antibodies, albumin, and clotting factors. Several factor
concentrate treatment products are available that are made from human plasma
proteins. All blood and parts of blood, such as plasma, are routinely tested for
viruses. The plasma is collected from many people, and then it goes through
several processes to separate it into components, such as clotting factors. The
clotting proteins are then made into a freeze-dried product, which 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. This
concentrate is genetically engineered using DNA technology. Commercially
prepared factor concentrates are treated to remove or inactivate blood borne
viruses. Additionally, recombinant factors VIII (8) and IX (9) do not contain any
plasma or albumin, and therefore, cannot spread any blood borne viruses
PEDIGREE CHARTS
BIBLIOGRAPHY

https://www.cdc.gov/ncbddd/haemophilia/facts.html