Hemophilia is a group of bleeding disorders that are caused by a lack of blood clotting factors, the proteins and enzymes needed to make blood clot. Blood clotting, or coagulation, is the body’s way of stopping blood loss.

Symptoms of hemophilia can vary in severity. For people with mild hemophilia, symptoms may be limited to easy bruising, nosebleeds, and excessive bleeding after an injury or surgery. Severe hemophilia may cause spontaneous bleeding, including life-threatening internal bleeding and brain bleeds.

Here’s what to know about the causes of hemophilia.

How Do Blood Clots Form?

To understand how a lack of clotting factor causes hemophilia, you first need to understand how blood clots form. The process of normal blood clotting is complicated and involves many steps. To put it simply, tissue damage triggers a chain reaction where one clotting factor is activated. That factor activates a second factor, which activates a third factor, and so on.

Ultimately, a blood clot is formed from blood platelets, red blood cells, and fibrin (a protein that binds the clot together). If any one of these required clotting factors is not available, then the chain reaction stops and blood clots cannot form to stop the bleeding. This leads to bleeding disorders.

What Causes the Different Types of Hemophilia?

There are two main types of hemophilia: hemophilia A (the most common) and hemophilia B. Hemophilia A (or classic hemophilia) is caused by low levels of clotting factor VIII (8), and hemophilia B (or Christmas disease) is caused by low levels of factor IX (9).

Some rare types of hemophilia are caused by a lack of other clotting factors, including factors I (1), II (2), V (5), VII (7), X (10), XI (11), XII (12), and XIII (13). In very rare situations, people can be missing more than one clotting factor.

The severity of hemophilia is determined by how severe the clotting factor deficiency is. Less clotting factor results in more severe disease.

Typically, not producing enough clotting factor or producing a faulty clotting factor (one that does not function properly) can result in a bleeding disorder. The most common inherited bleeding disorder, von Willebrand disease, can also cause a decrease in available factor VIII because of a deficiency of von Willebrand factor.

Genetic Causes of Hemophilia

Hemophilia is usually inherited, but hemophilia can also occur without a family history of the disease. Most hemophilia is congenital (present at birth), but in some people, symptoms may not occur until later in childhood or adulthood.

Inherited Genes

Most cases of hemophilia A and B are due to inherited mutations (variations) in the genes for factor VIII and factor IX. The genes for both of these factors are found in the X chromosome. The X and Y chromosomes determine sex (XX for female and XY for male), so mutations that occur in these chromosomes are not inherited the same way as other gene mutations.

Hemophilia A and B follow an X-linked recessive pattern of inheritance. This pattern means that all males who inherit the gene will develop the disease, and all of their female children will be carriers of the gene.

Females who are carriers of the gene don’t usually have symptoms. The children of carriers have a 50/50 chance of inheriting the gene. Some female carriers of hemophilia genes can develop mild disease, but females typically only develop disease if they inherit two copies of the mutated gene (one from each parent) or if one of their X chromosomes becomes randomly inactivated, leaving only one functional X chromosome.

Rarer types of hemophilia and related bleeding disorders, such as von Willebrand disease, follow different patterns of inheritance.

Spontaneous Mutations

Although hemophilia is usually caused by an inherited gene mutation, about one-third of people with hemophilia have no family history of the disease. Spontaneous mutations in the genes for factor VIII or IX are believed to be responsible for causing hemophilia in these people.

Acquired Hemophilia

Hemophilia is most often caused by genetic mutations, but the disorder can sometimes occur due to other conditions. Another type of hemophilia, called acquired hemophilia, occurs as a result of other diseases that prevent factor production or destroy clotting factors. Acquired hemophilia develops later in life and has many potential causes. About half of all cases of acquired hemophilia have no known cause.

Acquired hemophilia is most commonly caused by autoimmune disease, where the body makes antibodies called inhibitors that target and destroy clotting factors (usually factor VIII). Treating hemophilia with clotting factor concentrates can also cause the immune system to react by creating antibodies against those clotting factors.

Acquired hemophilia can occur with several autoimmune diseases, such as:

• Crohn’s disease
• Ulcerative colitis
• Multiple sclerosis
• Rheumatoid arthritis
• Systemic lupus erythematosus

Many other conditions can also cause acquired hemophilia, including:

• Cancer
• Diabetes
• Hepatitis
• Infections
• Lung disease

It can also be caused by taking certain medications or by pregnancy.

Talk With Others Who Understand

MyHemophiliaTeam is the social network for people with hemophilia and their loved ones. On MyHemophiliaTeam, more than 6,600 members come together to ask questions, give advice, and share their stories with others who understand life with hemophilia.

Have you been diagnosed with hemophilia? Do you know the cause? Share your experience in the comments below, or start a conversation by posting on your Activities page.