Haemophilia is a rare inherited blood disorder that affects the body’s ability to form blood clots properly, leading to prolonged bleeding episodes that can range from minor bruises to serious internal bleeding requiring immediate medical attention.

Epidemiology

Haemophilia is a relatively uncommon condition that affects approximately 2 out of every 10,000 men worldwide. Based on research using data from patients receiving care in federally funded haemophilia treatment centers in the United States during 2012 to 2018, about 33,000 males in the United States are living with this disorder^[2]. In Germany, it is estimated that there are 10,000 men with haemophilia, with about 3,000 to 5,000 of them having a severe form of the disease^[4].

The condition affects people from all racial and ethnic groups equally, with no particular population being more susceptible than others^[2]. Haemophilia A, which is caused by a lack of clotting factor VIII (a protein that helps blood form clots), is the most common type of haemophilia. It occurs about three to four times as frequently as haemophilia B, which involves a lack of clotting factor IX. Approximately half of those affected have the severe form of the condition^[2].

One of the most striking features of haemophilia is its strong gender pattern. The condition occurs mainly in males, though females can carry the changed gene that causes it and may sometimes experience bleeding symptoms themselves, though usually less severe than in men^[4]. This gender difference is due to the way the condition is inherited through genes on the X chromosome.

Causes

Haemophilia is most often caused by inherited changes in specific genes that provide instructions for making clotting factors. These are proteins in the blood that work together to stop bleeding by forming clots. When genes change or mutate, they don’t produce enough clotting factor, or the factor doesn’t work properly, and blood doesn’t clot as it should^[1].

The changed genes responsible for haemophilia are located on the X chromosome. Chromosomes are structures inside cells that carry genetic information and determine biological sex. Females have two X chromosomes (one from each parent), while males have one X chromosome from their mother and one Y chromosome from their father. This difference in chromosome makeup explains why the condition affects males and females differently^[1].

When a mother carries the changed gene on one of her X chromosomes, she can pass that chromosome to her children. A male child who inherits the chromosome carrying the changed gene will have haemophilia because he only has one X chromosome and no second, normal copy to compensate. A female child who inherits the changed gene will usually be a carrier of the disease or have only mild symptoms, such as unusually heavy periods. This is because she has a second X chromosome that doesn’t carry the changed gene and can partially compensate for the defective one^[1].

In some cases, haemophilia occurs without any family history of the condition. This happens when a spontaneous gene change occurs, meaning the genetic mutation develops on its own rather than being inherited from parents^[1]. Some children with haemophilia have no family history of the disorder at all^[19].

Very rarely, haemophilia can develop later in life rather than at birth. This is known as acquired haemophilia and is extremely uncommon. The majority of acquired haemophilia cases occur in middle-aged or elderly people, or in young women who have recently given birth or are in the later stages of pregnancy. This form of haemophilia often resolves with appropriate treatment^[2].

Risk Factors

The primary risk factor for haemophilia is having a family history of the condition. If someone in your family or your partner’s family has haemophilia, there is an increased chance that you or your children could have or carry the condition^[7]. Being male is another significant risk factor, as haemophilia is much more common in males than females due to the way the genetic changes are inherited through the X chromosome^[5].

For acquired haemophilia, which develops later in life, certain circumstances increase risk. Being middle-aged or elderly, being pregnant, or having recently given birth are all associated with higher chances of developing acquired haemophilia. Other risk factors for the acquired form include having immune system disorders, certain types of cancer, or experiencing allergic reactions to specific medications^[1].

It’s important to note that haemophilia cannot be caught from someone else like an infectious disease. You cannot develop haemophilia through contact with someone who has it. The condition is either inherited through genes or, in very rare cases of acquired haemophilia, develops due to the body producing specialized proteins called autoantibodies that attack and disable clotting factors^[1].

Symptoms

The symptoms of haemophilia vary greatly depending on whether someone has a mild, moderate, or severe form of the condition. The severity is determined by the amount of clotting factor in the blood. The lower the amount of clotting factor, the more likely bleeding will occur and the more serious the potential health problems^[2].

The most common symptom of haemophilia is unusual or excessive bleeding or bruising. This can manifest in several ways throughout the body. People with haemophilia may bleed for no apparent reason, such as sudden nosebleeds that occur without any injury. They may also bleed for a long time after a serious injury, surgery, or even a minor cut to the finger. Babies with haemophilia who bump their mouths on a toy may bleed from their mouths for extended periods^[1].

Bruising is another prominent symptom. Bleeding under the skin causes bruises to form, and people with haemophilia may develop large bruises after what seems like very minor injuries. Babies and toddlers may develop what are sometimes called “goose eggs” – large, round bumps that appear if they bump their heads. These bumps represent bleeding under the skin^[1].

Joint pain, swelling, and stiffness are particularly common and concerning symptoms. Internal bleeding may make joints ache, swell, or feel hot to the touch. This type of bleeding often affects the knees, elbows, and ankles^[2]. Babies with joint bleeding may have bruises or swollen areas on their arms and legs. They may become fussy or refuse to crawl because of the pain^[1].

Bleeding can occur in the mouth and gums, and it may be especially hard to stop after losing a tooth. Other symptoms include bleeding after circumcision in male babies, bleeding after receiving shots such as vaccinations, blood appearing in the urine or stool, and frequent nosebleeds that are difficult to stop^[2].

The symptoms of haemophilia usually begin to appear in early childhood, although in mild cases, symptoms may not be noticed until later in life or even adulthood. Mild haemophilia often causes few problems in everyday life and may only become noticeable during puberty or adulthood when bleeding after surgery or a deep cut lasts longer than normal. People with moderate haemophilia may have occasional prolonged bleeding, but usually only following surgery or an injury, with bleeding for no apparent reason being rare. In contrast, people with severe haemophilia often have internal bleeding that causes pain, with bleeding for no known reason being typical^[4].

For infants with severe haemophilia, the condition becomes noticeable from a very young age. Babies bruise very easily, and as children learn to walk and put more strain on their joints and muscles, bleeding starts occurring in those areas. Bleeding in joints is particularly painful, causing them to become swollen and hurt when moved, and they often become inflamed as well^[4].

Prevention

Since haemophilia is primarily an inherited genetic condition, there is no way to prevent someone from being born with it if they inherit the changed genes. However, there are important steps that can be taken to prevent bleeding episodes and complications for those who have the condition.

For families with a history of haemophilia, genetic counseling and testing are valuable prevention tools. If you’re at risk of having a child with haemophilia, a doctor may refer you to a genetic counselor to discuss the risks and options. Tests are available before, during, and after pregnancy for both the parent and the baby. These may include genetic tests to check if you carry the changed gene, blood tests during early pregnancy to check the sex of the baby (since boys are at more risk), and specialized tests during pregnancy such as chorionic villus sampling (CVS) or amniocentesis to check if the baby has haemophilia. After birth, a blood test can confirm whether the baby has the condition^[7].

For people living with haemophilia, preventing bleeding episodes is a crucial part of managing the condition. This involves making careful choices about physical activities and consistently wearing appropriate safety equipment such as seat belts, bike helmets, and sports safety gear^[19]. While people with haemophilia can participate in many normal activities, understanding which activities carry higher risks of injury and taking appropriate precautions is essential.

Regular comprehensive care at specialized haemophilia treatment centers is vital for preventing complications. These centers can provide preventative treatment plans, monitor for early signs of joint damage or other problems, and teach patients and families how to recognize and respond quickly to bleeding episodes. Early treatment of bleeding is critical to prevent long-term damage to joints and organs^[15].

Maintaining good overall health through proper nutrition, regular appropriate exercise, and maintaining a healthy body weight helps keep muscles strong and joints flexible, which can reduce the risk of bleeding episodes. Good dental hygiene, including regular brushing, flossing, and dental visits, is also important because a healthy mouth is less likely to have bleeding problems^[16].

Pathophysiology

To understand what goes wrong in haemophilia, it’s helpful to know how blood normally clots. When a blood vessel is injured, the body initiates a complex process to stop bleeding. Blood contains many proteins called clotting factors that work together in a sequence, like a cascade, to form a blood clot. Each factor activates the next one in the chain until a stable clot is formed^[1].

In haemophilia, this clotting cascade is interrupted because one of the essential clotting factors is either missing or present in insufficient amounts. In haemophilia A, the body lacks adequate clotting factor VIII (eight), while in haemophilia B, there isn’t enough clotting factor IX (nine). Without these factors, blood cannot clot properly^[19].

Contrary to what some people think, individuals with haemophilia don’t actually bleed faster than people without the condition. The blood flows out at the same rate initially. The problem is that the bleeding continues for much longer because the blood cannot form the stable clot needed to seal the wound. The clot that does form may be incomplete or so thin that it doesn’t effectively stop the bleeding^[19].

For small cuts and scrapes, where only simple clotting is needed, people with haemophilia often stop bleeding relatively normally. The real problems occur when a more complex clot is needed. This is particularly true for internal bleeding, where blood can leak into joints, muscles, or organs without any external signs. Over time, repeated bleeding into the same joint can cause chronic damage^[3].

A joint that has already been affected by internal bleeding is more likely to bleed again in the future. This repeated bleeding can progressively deform the joint, causing it to stiffen and slowly lose function. This process is called hemophilic arthropathy and represents one of the most significant long-term complications of the condition^[4].

The severity of symptoms depends directly on how much clotting factor is present in the blood. Healthcare providers classify haemophilia as mild, moderate, or severe based on the level of clotting factors. People with severe haemophilia have very low levels of clotting factor and experience frequent bleeding episodes, often without any obvious injury. Those with moderate levels have occasional bleeding, usually after some trauma. People with mild haemophilia have enough clotting factor that they may only have problems with excessive bleeding after surgery or significant injuries^[1].