Haemophilia

Haemophilia is a rare inherited blood disorder in which blood does not clot properly, causing prolonged bleeding from injuries and sometimes internal bleeding that can damage joints and organs.

Table of contents

• What Is Haemophilia?
• Types of Haemophilia
• Signs and Symptoms
• What Causes Haemophilia
• Who Is at Risk
• How Haemophilia Is Diagnosed
• Treatment Options
• Living with Haemophilia

What Is Haemophilia?

Haemophilia is a rare blood disorder that keeps your blood from clotting normally^[1]. When you have haemophilia, you don’t have enough clotting factors (proteins that help your blood form clots) to prevent uncontrollable bleeding^[1]. If you have haemophilia, a minor injury may cause you to bleed a lot, and you might bruise easily^[1].

The condition most often happens when you inherit certain genetic changes that keep your body from making clotting factors^[1]. People with haemophilia are born with the disorder, and it lasts all of your life^[19]. You cannot catch it from someone else^[19]. There is no cure for haemophilia at this time, but newer treatments prevent or reduce how often you experience bleeding^[1].

Haemophilia 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, and death which can occur if the bleeding cannot be stopped or if it occurs in a vital organ such as the brain^[2].

Types of Haemophilia

Healthcare providers classify haemophilia based on which clotting factor is missing or low in your blood^[1]. The most common types are:

• Haemophilia A (classic haemophilia): This is the most common type. You may develop this condition because you have low levels of clotting factor 8 (factor VIII)^[1][2].
• Haemophilia B (Christmas disease): You may have this type if you don’t have enough clotting factor 9 (factor IX)^[1][2].
• Haemophilia C: This is also known as factor 11 (factor XI) deficiency. It’s the least common type of haemophilia^[1].

Haemophilia A is about three to four times as common as haemophilia B^[2]. Haemophilia A and B have the same symptoms, but the medicines used to treat each type are different^[7].

Healthcare providers also classify haemophilia as being severe, moderate or mild, based on the number of clotting factors in your blood^[1]. 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^[2]. About half of those affected have the severe form^[2].

Signs and Symptoms

The most common symptoms are unusual or excessive bleeding or bruising^[1]. How much bruising or bleeding you experience depends on whether you have a severe, moderate or mild form of the condition^[1]. Signs and symptoms of haemophilia vary, depending on your level of clotting factors^[3].

Common symptoms include:

• Bleeding: You may bleed for no apparent reason, like a sudden nosebleed. You may bleed for a long time after a serious injury, surgery or a cut finger^[1]. This can lead to spontaneous bleeding as well as bleeding following injuries or surgery^[2]. Babies with this condition who bump their mouths on a toy may bleed from their mouths^[1].
• Bruises: Bleeding under your skin causes bruises. People with haemophilia may develop large bruises after minor injuries^[1]. Babies and toddlers may have goose eggs (large, round bumps) that develop if they bump their heads^[1].
• Joint pain: Internal bleeding may make your joints ache, swell or feel hot to the touch^[1]. This often affects the knees, elbows, and ankles^[2]. Bleeding in joints is very painful, and joints often become inflamed as well^[4]. Babies may have bruises or swollen areas on their arms and legs. They may be fussy or refuse to crawl^[1].
• Bleeding of the mouth and gums, including bleeding that is hard to stop after losing a tooth^[2][5].
• Bleeding after circumcision (surgery performed on male babies to remove the hood of skin covering the head of the penis)^[2].
• Bleeding after having shots, such as vaccinations^[2].
• Blood in the urine or stool^[2][5].
• Frequent and hard-to-stop nosebleeds^[2][5].

There are three levels of severity in haemophilia, depending on the likelihood of bleeding. Mild haemophilia often hardly causes any problems in everyday life and may only become noticeable in puberty or adulthood when bleeding after surgery or a deep cut lasts longer than normal. Someone with moderate haemophilia may have occasional long-lasting bleeding, but usually only following surgery or an injury. People who have severe haemophilia often have internal bleeding that causes pain, with bleeding for no known reason being typical^[4].

Very rarely, severe haemophilia causes bleeding into your brain. This is a life-threatening condition^[1]. A simple bump on the head can cause bleeding into the brain for some people who have severe haemophilia^[3]. Symptoms are persistent headaches, double vision or feeling very tired^[1]. If you have haemophilia and have these symptoms, get medical care right away^[1].

What Causes Haemophilia

The condition most often happens because you inherit changed genes from your biological parents^[1]. Haemophilia is usually caused by a mutation or change in one of the genes that provides instructions for making the clotting factors needed to form a blood clot^[2]. Genes carry the clotting factor instruction manual. When genes change, they don’t make enough clotting factor, and your blood doesn’t clot^[1].

This change or mutation can prevent the clotting factor from working properly or to be missing altogether^[2]. Haemophilia is caused by the lack of a particular protein in the blood that helps it to clot. People with haemophilia A don’t have clotting factor VIII (eight), while people who have haemophilia B lack clotting factor IX (nine)^[4].

People inherit the change in an X-linked recessive manner^[1]. Here’s how that happens:

• The changed genes are on X chromosomes. Chromosomes decide your sex^[1].
• Females have two X chromosomes. They inherit one from their biological mother and one from their biological father. Males inherit one X chromosome from their biological mother and one Y chromosome from their biological father^[1].
• A mother with a changed gene on one chromosome can pass that chromosome on to a biological child^[1].
• A male child who inherits a chromosome carrying the changed gene will have haemophilia because they only have one X chromosome^[1].
• A female child who inherits the changed gene will carry the disease or have mild symptoms like unusually heavy periods. That’s the case because they have a second chromosome that doesn’t carry the changed gene^[1].

The cells in women’s bodies contain two X chromosomes, whereas the cells in men’s bodies only contain one. So if a woman has a defective gene on one of her X chromosomes, having a normal gene on the other X chromosome can usually prevent any blood clotting problems. It’s very rare for both genes to be defective in women. But if a man has a defective gene, it can’t be overridden by a normal one, so haemophilia is more common in men^[4].

Haemophilia occurs mainly in males but females can carry the gene that causes it and may or may not have bleeding problems. Some children with haemophilia have no family history of the disorder^[19]. A spontaneous gene change may cause haemophilia in these cases^[1].

Haemophilia that is not inherited is called acquired haemophilia. It is rare^[5]. It happens when your body makes specialized proteins called autoantibodies that attack and disable a clotting factor. This can happen because of pregnancy, immune system disorders, cancer, or allergic reactions to certain medicines. Sometimes the cause is unknown^[5]. The majority of acquired haemophilia cases occur in 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 (goes away) with appropriate treatment^[2].

Who Is at Risk

Inherited haemophilia occurs in about 1 of every 5,000 male births^[2]. Based on a study that used data collected on patients receiving care in federally funded haemophilia treatment centers during the period 2012–2018, about 33,000 males in the United States are living with the disorder^[2]. It is estimated that there are 10,000 men with haemophilia in Germany, about 3,000 to 5,000 of whom have a severe form of the disease^[4].

Haemophilia is much more common in people who were born male since they can get it with a change to the gene on one X chromosome^[5]. People who have a family history of haemophilia are also at higher risk^[5]. Haemophilia affects people from all racial and ethnic groups^[2].

How Haemophilia Is Diagnosed

To find out if you have haemophilia, your health care provider will ask about your medical history, including your symptoms and other health conditions you may have, and ask about your family history to find out if you have relatives who have or had haemophilia^[5]. They will do a physical exam to look for signs of haemophilia, such as bruising^[5].

Clotting-factor tests are used to help diagnose haemophilia^[2]. These tests can reveal a clotting-factor deficiency and determine how severe the haemophilia is^[9]. The tests check the amount of clotting factor in your blood^[1].

Severe cases of haemophilia usually are diagnosed within the first year of life. Mild forms might not be apparent until adulthood. Some people learn they have haemophilia after they bleed excessively during a surgical procedure^[9].

For people with a family history of haemophilia, genetic testing might be used to identify carriers to make informed decisions about becoming pregnant. It’s also possible to determine during pregnancy if the fetus is affected by haemophilia. However, the testing poses some risks to the fetus^[9].

If you’re at risk of having a child with haemophilia, a doctor may refer you to a genetic counsellor to discuss the risks and options. Tests are available before, during and after pregnancy for you and your baby. These tests may include a genetic test to check if you carry the altered gene, a blood test during early pregnancy to check the sex of the baby (boys are at more risk of haemophilia), chorionic villus sampling (CVS) or amniocentesis tests during pregnancy to check if your baby has haemophilia, and a blood test from your baby after birth to check if they have haemophilia^[7].

Treatment Options

The key to best outcomes is to prevent and treat bleeding^[19]. Haemophilia is usually treated with injections of clotting factor to replace the missing clotting factor in your blood^[7]. The main treatment for severe haemophilia involves replacing the clotting factor you need through a tube in a vein^[9].

The standard way to treat both haemophilia A and B is to replace the missing blood clotting factor so that the blood can clot properly. One way to do this is by infusing (injecting into a vein) commercially prepared clotting factor concentrates^[8].

Haemophilia is treated in 2 main ways:

• If you have severe haemophilia, you’ll usually need injections up to 3 times a week to prevent bleeding (preventative or prophylactic treatment). You can usually do these injections yourself at home^[7]. Prophylaxis has been shown in many studies to prevent or at least reduce the progression of damage to target sites, such as joints^[12].
• If you have mild or moderate haemophilia, you’ll usually only need treatment to stop or reduce bleeding after it starts (on-demand treatment)^[7]. You may also need treatment before having surgery or dental work^[7]. Healthcare providers typically prescribe treatment products for episodic care or prophylactic care. Episodic care is used to stop a patient’s bleeding episodes^[8].

This replacement therapy can be given to treat a bleeding episode in progress. It can also be given on a regular schedule at home to help prevent bleeding episodes. Some people receive continuous replacement therapy^[9]. People with haemophilia can learn how to perform infusions themselves so that they can stop bleeding episodes and, by performing the infusions on a regular basis, can even prevent most bleeding episodes. Giving factor treatment products at home means that bleeds can be treated more quickly, resulting in less serious bleeding and fewer side effects^[8].

The two main types of clotting factor concentrates available are plasma-derived factor concentrates and recombinant factor concentrates. Plasma-derived factor concentrates are made from human plasma proteins. Recombinant factor concentrates are genetically engineered using DNA technology and do not come from human plasma^[8]. Commercially prepared factor concentrates are treated to remove or inactivate bloodborne viruses. Recombinant factors VIII and IX do not contain any plasma or albumin, and therefore, cannot spread any bloodborne viruses^[8].

For haemophilia A, another treatment method is a non-factor product that stands in for, or replaces the function of, the missing factor VIII. This treatment is given by injection under the skin that can be given by people with haemophilia themselves^[8].

Other therapies include:

• Desmopressin: In some forms of mild haemophilia, this hormone can stimulate the body to release more clotting factor. It can be injected slowly into a vein or used as a nasal spray^[9].
• Emicizumab (Hemlibra): This is a newer drug that doesn’t include clotting factors. This drug can help prevent bleeding episodes in people with haemophilia A^[9].
• Clot-preserving medications: Also known as anti-fibrinolytics, including tranexamic acid, these medications help prevent clots from breaking down^[9][7].

Some people who infuse with clotting factor concentrates may develop an inhibitor. Inhibitors make it more difficult to stop a bleeding episode because they prevent the treatment from working^[8]. If this happens, your haemophilia team will work with you to find you a more suitable treatment^[7].

Treatment of patients with haemophilia ideally should be provided through a comprehensive haemophilia treatment center (HTC). These centers, which are found in many cities, follow a multidisciplinary approach, with specialists in hematology, orthopedics, dentistry, and surgery; nurses; physiotherapists; social workers; and related allied health professionals^[12]. An HTC provides patients with the care and education to address all issues related to the disorder. The team consists of physicians (hematologists or blood specialists), nurses, social workers, physical therapists, and other healthcare providers who are specialized in the care of people with bleeding disorders^[8]. Patients treated at comprehensive care clinics have been shown to have better access to care, less morbidity, and better overall outcome^[12].

Living with Haemophilia

There is no cure for haemophilia at this time, but there is medicine people can take. This medicine helps them stop bleeding so they can do most of the things everyone else does. By using the medicine and visiting a haemophilia treatment center regularly, the person with haemophilia can expect to live a long and happy life^[19]. With proper treatment, most people with haemophilia lead long, full, and productive lives^[16].

It is very important for you to take an active role in managing your own, or your child’s, everyday care. To make important decisions, you need to know about haemophilia, understand the treatment options, and then make the best possible choices for your health or the health of your child^[15].

Everyday strategies for living with haemophilia include:

• Find good medical care: 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 haemophilia treatment center (HTC)^[15].
• Learn to self-infuse: Being able to administer your own treatment means you can take care of bleeds yourself and be independent^[16].
• Treat bleeds early: Don’t hide bleeds or wait to treat them. Over time, delayed treatment can damage your joints and restrict your mobility^[16].
• Eat right and exercise: Commit to a nutritious diet and physical fitness program to keep your muscles strong, your joints flexible, and your body healthy^[16].
• Brush and floss regularly: A healthy mouth is less likely to have bleeding problems, so brush, floss, and visit your dentist^[16].
• Make good choices of activities: Wear good safety equipment such as seat belts, bike helmets and sports safety gear^[19].
• Keep an emergency kit ready: Having the necessary supplies on hand in case of a bleed can significantly reduce stress and provide peace of mind^[17].

You can contact local bleeding disorder organizations to get in touch with families in your area who have been affected by haemophilia. There are local chapters and associations in many areas. By finding support within your community, you can learn more about resources available to meet the needs of families and people with haemophilia. Securing support and community resources can help increase your confidence in managing haemophilia, enhance your quality of life, and assist you in meeting the needs of family members^[15].

A joint that has already been affected by internal bleeding is likely to be affected again. Recurrent bleeding can deform a joint, stiffening and slowly destroying it^[4]. When recovering from a joint or muscle bleed, following appropriate steps for sprains and strains can also help^[7].