About Hemophilia

ABOUT HEMOPHILIA

If you’ve heard the word ‘hemophilia’, a lot may be running through your mind. What is it? Can I give it to my child? If my child has it, can their life be ‘normal’? Arm yourself with the facts. The more you know, the better you’ll understand how it may affect you or your loved one over the course of your lives.

What is Hemophilia ? - Hemophilia is a genetic (inherited) disorder in which a person’s blood cannot properly clot. Because of this, bleeding lasts for a longer time. Minor cuts and scrapes are usually not serious. But, if there is a large cut or bleeding happens inside the body, this can be serious.
Frequency of Hemophilia - Hemophilia is very rare. Only 1 in 10,000 people worldwide – and about 17 people in Maldives have hemophilia A or B, the most common form. Because of the way the gene is passed on in families, the most severe forms of hemophilia usually affect males.Hemophilia doesn’t discriminate: people from different races and ethnicities can be affected.
Testing for Hemophilia - To diagnose hemophilia, a person needs to be tested. These tests will also show how severe it is. If there’s a family history, testing can be done soon after birth. In 30% of cases, a child is born with hemophilia when there is no family history.
Hemophilia A,B & C - It’s important to know which type of hemophilia your loved one has, so that you know which clotting factor they are lacking, or have too little of. This can affect both their symptoms and treatment.
Genetics "The Basics" - To understand how hemophilia is inherited within families, it’s helpful to learn some of the basics of genetics. This includes how the hemophilia gene is passed on, the likelihood of this, why boys are usually affected, and what it means to be a carrier.
What causes Hemophilia - Hemophilia is caused by a problem (or mutation) with the gene(s) responsible for making clotting factors. As a result, people with hemophilia bleed for a longer time after an injury. Hemophilia is passed on through genes located on the X chromosome, which explains why males are much more likely to get it.
Inhibitors / Antibodies - To help prevent bleeding, people with hemophilia can be given infusions (injections directly into the blood) of the clotting factor they lack. In most cases, this treatment works well. But sometimes, a person’s immune system develops inhibitors, which are neutralizing antibodies that try to fight the treatment. Fortunately, there are treatments available to help manage inhibitors.

What is Hemophilia ?

Hemophilia is a rare genetic (inherited) disorder in which a person’s blood cannot clot properly.

Because of this, when a person with hemophilia gets a large cut or suffers internal injuries, he’ll bleed for a longer time and have difficulty healing.

HOW THE BLOOD CLOTS IN PEOPLE WITH AND WITHOUT HEMOPHILIA

Adapted from the National Hemophilia Foundation. Available at http://www.hemophilia.org

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Hemophilia can range from mild to severe

It is important to know what type of hemophilia you or your loved one has. This will tell you whether it’s a Factor VIII deficiency (Hemophilia A), Factor IX deficiency (Hemophilia B), or a more unusual type (like Hemophilia C). It’s also important to know how severe their hemophilia is. Two people with hemophilia can have very different symptoms depending on its severity. The severity of hemophilia depends on how much clotting factor is “turned on”, or active, in the blood.

The table below shows how a person with hemophilia A or B can have mild, moderate, or severe symptoms depending on how much Factor VIII or IX is working in their blood.

Frequency of Hemophilia

Hemophilia is a very rare condition.

Only 1 in 10,000 people worldwide – and about 14 people in Maldivians – have hemophilia A, the most common form. Hemophilia B affects only 1 in 50,000, or about 3 Maldivians. Hemophilia doesn’t discriminate: people from different races and ethnicities can be affected.

Because of the way the gene is passed on through families, hemophilia usually affects males. The most severe forms of hemophilia affect males almost exclusively. But, women who are carriers of the hemophilia gene can show mild symptoms.

People with hemophilia can live long, healthy lives so there are many older adults living with the condition today.

Testing for Hemophilia

Hemophilia is usually inherited, so often there is a known family history of the condition. But sometimes – there isn’t one. This is why it may be important for some women to get tested to see if they’re a carrier.

TESTS TO DIAGNOSE HEMOPHILIA

If there is a family history of hemophilia, some parents choose to test their babies before birth or shortly afterwards. Umbilical cord blood testing can detect low levels of Factor VIII (lacking in hemophilia A); but testing for Factor IX (lacking in hemophilia B) happens at 6 months, since it takes more time for this clotting factor to develop. Prenatal testing may involve certain risks that should be discussed with your doctor. You can then make an informed decision about whether it’s right for you and your family.

The decision to have your baby tested, either before or after birth, is yours. Genetic counselling is a good option to parents considering testing. Genetic counsellors can provide valuable information, support and alternatives – in a confidential manner.

If there is no family history of hemophilia, and your child shows the signs of a bleeding disorder (such as bleeding in the gums or tongue or frequent bruising from falls), your doctor may want to test your child for hemophilia A or B. They will take a blood sample from your child and measure the amount of the two clotting factors, Factor VIII and Factor IX in the blood. The tests will show:

If your child has hemophilia
What type of hemophilia they have
How severe it is, based on how much clotting factor is missing

If the lab tests show low levels of a different type of blood protein, this may mean your child has a bleeding disorder other than hemophilia (such as von Willebrand disease). No matter the diagnosis, your doctor will discuss the results with you, and the steps you can take to move forward.

DEALING WITH A DIAGNOSIS OF HEMOPHILIA

It can be a very difficult time hearing that your child has hemophilia. Feelings can vary from shock and anger, to denial and grief. Some parents also feel guilt that they “gave it to their child”, and fear doing the same thing again. With an unexpected diagnosis, in particular, you may be scared and wonder “why us? ”

It’s normal to go through these emotions: but know there is support available. Your local Hemophilia Treatment Centre (HTC) can offer invaluable support and help establish a comprehensive team of professionals to guide you through each stage of the child's development. The HTC can also arrange for genetic counselors and/or social workers to meet with you.

TESTING TO SEE IF YOU CARRY THE HEMOPHILIA GENE

If your baby or young child is diagnosed with hemophilia in a family with no previous history, healthcare professionals will discuss with you if would like to have genetic testing to determine if someone in the family is a carrier of the hemophilia gene. There are two reasons to test a potential carrier:

To measure a woman’s factor level; if it’s low, precautions may be needed to prevent abnormal bleeding
To know whether a woman carries the gene for hemophilia

Various types of tests can be done, at different points in a woman’s life. Talk to your healthcare provider about different tests available, what they involve, and when they can be done. HTCs are the best place to get testing done, because they routinely do this type of testing and can offer education and support. Your doctor or nurse can help you locate one near you.

TO TEST OR NOT TO TEST: THE ROLE OF GENETIC COUNSELLING

A decision to get tested for carrier status has implications for the entire family and needs careful thought and discussion. Your healthcare team can help you through this process and recommend genetic counselling. Genetic counsellors can provide strategies on how to inform other at-risk female relatives such as sisters, daughters, or nieces – and provide additional support. At the parents' request, most social workers and genetic counsellors will meet with the extended family. Genetic counsellors are available through your HTC, or through your hospital.

An unexpected diagnosis of hemophilia can be a fearful experience. Know that children born with hemophilia today can look forward to long, healthy, active lives. In fact, their lifespan is considered to be nearly normal – so that they can look forward to having children of their own.

Hemophilia A, B & C

It’s important to know which type of hemophilia your loved one has, so that you know which clotting factor they are lacking, or have too little of. This can affect both their symptoms and treatment.

Our bodies have different clotting factors that are needed to stop bleeding after an injury. People with hemophilia A are missing or have too little of a clotting factor called Factor VIII. This is the most common form. Hemophilia A has two other names:

Classic hemophilia, because it is the most common of the factor deficiencies.
Factor VIII deficiency hemophilia, because Factor VIII is the clotting factor that is lacking.

People with hemophilia B are missing, or have too little, of a clotting factor called Factor IX. This bleeding disorder has similar symptoms to hemophilia A, but is much less common.

People with hemophilia C lack the Factor XI clotting protein. It is very rare, and even researchers don’t know a lot about it. Unlike hemophilia A and B which affect mainly boys, hemophilia C affects both girls and boys equally because it is inherited in a different way.

Genetics: The Basics

Hemophilia is generally considered a genetic disorder, meaning that it is caused by a gene that does not work the way it should because it is mutated, or changed from normal.

To understand how hemophilia is inherited within families, it’s helpful to learn some of the basics of genetics.

Genetics is the study of how genes are passed from one generation to the next. Every cell in our body has genes. Our genes are what make us who we are – they form our body’s blueprint. Things like eye, skin and hair colour are all determined by our genes. And we have a lot of them – about 20,000 to 25,000. Our genes contains DNA, which is a “code” that instructs the cells in our bodies to produce substances called proteins. The DNA needs to be in a specific sequence to produce the protein properly There are thousands of proteins that do different things in our bodies. Clotting factors, for example, are types of proteins.

WHAT ARE CHROMOSOMES?

A chromosome is a collection of genes. There are 23 pairs of chromosomes in a human cell: one of each pair is inherited from your mother and the other from your father. So, our chromosomes determine what traits we inherit from our parents.

WHAT ARE SEX-LINKED GENES?

One pair of chromosomes are the sex chromosomes: "X" and "Y." Women have two X chromosomes and men have an X and a Y chromosome. Genes that are carried on the X chromosome are called X-linked, or sex-linked genes.

The genes that control the production of Factor VIII and IX are part of the X chromosome. This is why hemophilia A and B are considered “sex-linked disorders”, which means one sex (males) is predominantly affected.

X VS. Y: THE DIFFERENCE BETWEEN GIRLS AND BOYS

To understand how hemophilia is inherited, we need to understand how a baby is conceived. When a child is conceived, a male sperm fertilizes a female egg. The woman's egg contains two X chromosomes, while a man's sperm has both an X and a Y chromosome. Each parent contributes equally to their new child: a father passes on either an X or a Y, while a mother passes on one of her Xs. So at conception, there are four possible ways the egg and sperm cells can combine, which determines the child’s sex:

The mother always passes on an X chromosome, so it’s the father that determines the baby’s sex:

What Causes Hemophilia?

Hemophilia is an inherited disorder – typically passed on to boys through the X chromosome. But, hemophilia can also occur when there is no family history.

Remember how DNA ‘codes’ proteins, like clotting factors? When there is a change in the DNA sequence, called a mutation, the way proteins are made can be affected. Hemophilia is caused by a mutation in the gene responsible for producing clotting factors. The type of hemophilia a person has depends on which gene is disrupted. Researchers don’t fully understand why mutations like these happen.

HOW HEMOPHILIA IS INHERITED

So, why are males much more likely to have hemophilia? It’s because hemophilia is passed on through the X chromosome. Males are ‘XY’ so they only have one X chromosome that they inherit from their mother. So, if his X chromosome contains the gene responsible for hemophilia, there is no ‘normal’ X chromosome to ‘override it.’ Females, on the other hand, have two X chromosomes (are ‘XX’), so there will usually be one ‘normal’ X chromosome to protect her from having severe hemophilia. It is very rare for a girl to be born with severe hemophilia.

WHAT DOES BEING A CARRIER MEAN?

There are some women who have one hemophilia gene and, because of this, bleed longer than a normal person. Usually, women with one hemophilia gene are carriers. A carrier is a woman who may not show any symptoms, but carries the gene mutation for hemophilia and can pass it on to her children. Women who have a family history of hemophilia, or show mild symptoms of a bleeding disorder, may choose to be tested to see if they are a carrier.

THE CHANCES OF PASSING ON THE HEMOPHILIA GENE

There are many different ways the hemophilia gene can be passed on. Here are two scenarios:

Scenario 1 (see below): If a woman who is a carrier has a son with a man without the hemophilia gene, the son has a 50/50 chance of developing hemophilia. If they have a daughter, she will not have hemophilia, but has a 50% chance of being a carrier.

Scenario 2 (see below): If a man with hemophilia has children with a woman who is not a carrier, none of their sons will have hemophilia because the father passes along his normal Y chromosome and the mother passes on a normal X. However, all of the couple's daughters will be carriers.

POSSIBLE PATTERNS OF INHERITANCE

SCENARIO 1

SCENARIO 2

Adapted from Centers of Disease Control: Hemophilia. Available at: http://www.cdc.gov

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A girl can be born with severe hemophilia only when:

A woman who is a carrier has a child with a man who has hemophilia – so both pass on a mutated X chromosome.
A woman who is a carrier has a child with a man who does not have hemophilia AND a second new spontaneous hemophilia mutation happens when the child is conceived.
A man who has hemophilia has a child with a woman who is not a carrier AND a second new spontaneous hemophilia mutation happens when the child is conceived.

These three situations are extremely rare.

HEMOPHILIA WHEN THERE IS NO FAMILY HISTORY

In about 3 cases in every 10, a son will be born to a family that has no history of hemophilia. There are two reasons why this might happen:

An unknown family history - It is possible that hemophilia was in the family for generations, but went undetected because no son with hemophilia was born in living memory.
A ‘spontaneous’ genetic mutation - Some cases of hemophilia are caused by a new, or spontaneous, genetic mutation. This means that a genetic problem unexpectedly happens in a person, for no known reason. This could happen either in the mother at the time she was conceived (making her a silent carrier), or in the child at the time of conception (so his mother is not a carrier). Researchers don’t fully understand why these mutations happen, and why they happen in some people and not others.

Because there isn’t always a history of it, hemophilia can affect any family. If you notice the signs and symptoms of a bleeding disorder after a child’s birth, talk to your doctor right away. Testing can be done to see if it is hemophilia.

Inhibitors/Antibodies

A common treatment for hemophilia is infusion therapy, or injections into the blood, of the clotting factor a patient needs to help stop or prevent bleeding. As with any medication, complications sometime can occur.

To help prevent bleeding, people with hemophilia can be given infusions (injections directly into the blood) of the clotting factor they lack. Your child’s doctor will determine which clotting factor they are missing and determine if factor infusions are appropriate for them. In most cases, this treatment works well. But sometimes, a person’s immune system develops inhibitors, which are antibodies that try to fight the treatment and “inhibit” it from working properly. This is a very serious complication of hemophilia because it means factor replacement therapy is no longer effective. Without treatment, severe internal bleeding can occur. But there are treatments available to help manage inhibitors.

WHO DEVELOPS INHIBITORS, OR ANTIBODIES?

Inhibitors are most common in young children with severe hemophilia A. They usually appear within the first few infusions of Factor VIII therapy. About 1 in 3 of people with severe hemophilia A will develop inhibitors. People with mild to moderate hemophilia A have a lower chance of developing inhibitors – about 1 in 50 – and it usually happens during adulthood. Inhibitors are even more rare in people with hemophilia B (1 in 100), but the complications can be more serious. Other people at a higher risk of developing inhibitors include people:

➥ with a family member with inhibitors

➥ of African descent

Researchers don’t know exactly why some people develop inhibitors, while others do not. People may also have different types of inhibitors: for some, they aren’t very severe and are inactive (have no effect) for periods of time. For others, they are more serious, and don’t go away without effective treatment.

HOW DO YOU KNOW IF SOMEONE HAS DEVELOPED INHIBITORS?

If someone receives an infusion of clotting factor, and they do not respond in the usual way, this could be a sign of inhibitors. For example, a bleed may not properly clot, or it may take 2 or 3 infusions before blood clots properly. A blood test will need to be done to see if inhibitors are present, and treatment can be started as soon as possible to help manage them.

The good news is that in 2 out of 3 cases, inhibitors disappear – either on their own, or after treatment, within 9 months (on average). For others, inhibitors persist and are a serious problem.

TREATING INHIBITORS

Managing inhibitors is complex and one of the biggest challenges facing people with hemophilia. Doctors often treat inhibitors by using something called immune tolerance therapy (ITT), which tries to “teach” the body to stop fighting factor replacement therapy. Very high doses of factor VIII are used in ITT. Sometimes, a doctor will have to try different regimens of ITT to find optimal results. Not everyone will respond to ITT. ITT is usually not effective in people with hemophilia B.

If ITT doesn’t work, other treatment options can be tried. These treatments focus on preventing bleeding, rather than fighting the inhibitors.

COPING WITH INHIBITOR THERAPY

ITT can be very long – up to 3 years – which can be physically and emotionally taxing on a patient and their family. It can be hard to see your child endure more injections. And, it can be frustrating and discouraging: Why did this happen? Why did treatment just ‘stop working? What now?

It’s important to work closely with your healthcare team and your HTC to help get through these challenges. They can help answer your questions and manage expectations. You can’t do everything alone – lean on those around you for support, encouragement and guidance.