What is the cause of the bleeding disorder hemophilia?

October 1, 2025 •

4 min read

Hemophilia is a rare inherited bleeding disorder in which the blood does not clot properly, and is most commonly caused by an inherited genetic mutation. Approximately one-third of diagnosed cases, however, are caused by a spontaneous new mutation. There are also rare instances of acquired hemophilia where the immune system attacks a person's own clotting factors.

Quick Summary

Hemophilia is primarily caused by an inherited genetic mutation leading to a deficiency of specific clotting factors, but it can also be a rare acquired autoimmune condition. The most common types, A and B, follow an X-linked recessive pattern.

Key Points

Genetic Mutations: The primary cause of hemophilia is an inherited genetic mutation, typically affecting clotting Factor VIII (Hemophilia A) or Factor IX (Hemophilia B).
X-Linked Inheritance: Hemophilia A and B are X-linked recessive disorders, meaning the mutated gene is on the X chromosome and primarily affects males.
Acquired Form: In rare cases, hemophilia can be acquired later in life due to an autoimmune response that attacks the body's own clotting factors.
Carrier Status: Females with one copy of the mutated gene are typically carriers but can experience mild symptoms due to varied X-inactivation.
Spontaneous Mutations: Approximately one-third of congenital hemophilia cases arise from a new, spontaneous genetic mutation with no prior family history.
Multiple Causes: The underlying cause can be inherited, spontaneous genetic changes, or an acquired autoimmune condition, all leading to a deficiency in blood clotting.

The Role of Clotting Factors

To understand the cause of hemophilia, one must first understand the blood clotting process. When a blood vessel is injured, a complex sequence of chemical reactions, known as the coagulation cascade, is triggered. This cascade involves numerous proteins called clotting factors, which work together to form a solid blood clot and stop the bleeding. People with hemophilia are missing or have very low levels of a particular clotting factor, which prevents the cascade from completing properly and results in prolonged bleeding.

Inherited Hemophilia: A Genetic Mutation

The most common cause of hemophilia is an inherited genetic mutation passed from parents to their children. The severity of the disorder is determined by the amount of the specific clotting factor present in the blood, which is dictated by the genetic mutation.

Genetic Basis: X-linked Recessive Inheritance

The genes responsible for producing the most common clotting factors—Factor VIII (F8) and Factor IX (F9)—are located on the X chromosome. This is why Hemophilia A (deficient Factor VIII) and Hemophilia B (deficient Factor IX) are known as X-linked recessive disorders.

Males (XY) inherit their X chromosome from their mother. If this X chromosome carries the mutated gene, a male will have hemophilia because they do not have a second X chromosome to provide a normal copy of the gene.
Females (XX) inherit one X chromosome from each parent. For a female to have severe hemophilia, both X chromosomes would need to carry the mutation, which is very rare. More commonly, a female with one mutated gene and one normal gene is a carrier. Carriers can pass the gene to their children and, in some cases, may experience milder bleeding symptoms, especially if there is a phenomenon called "skewed X-inactivation".
De Novo Mutations: While typically inherited, approximately one-third of hemophilia cases are caused by a new, spontaneous genetic mutation that occurs in the affected individual and is not present in their mother's X chromosome.

The Result of the Mutation

Genetic mutations affect the production and function of clotting factors. These can include point mutations, gene deletions, insertions, or inversions, all disrupting the genetic code for the clotting factor protein.

Acquired Hemophilia: An Autoimmune Response

Acquired hemophilia is a very rare bleeding disorder where the immune system creates autoantibodies that target and neutralize specific clotting factors, most often Factor VIII. It is not genetic and typically affects older adults. Approximately half of acquired hemophilia cases have an unknown cause (idiopathic), while the other half are linked to conditions like autoimmune diseases, cancer, pregnancy, or medication reactions.

Comparison of Inherited and Acquired Hemophilia


Feature	Inherited Hemophilia	Acquired Hemophilia
Cause	Genetic mutation in the gene for a specific clotting factor.	Autoimmune response where the body produces antibodies against its own clotting factor.
Onset	Present from birth.	Develops later in life, typically in middle-aged or older adults.
Inheritance	X-linked recessive pattern for types A and B.	Not inherited; not passed from parent to child.
Genetics	Caused by a mutation in a specific gene (F8 for Type A, F9 for Type B).	Not caused by a gene mutation.
Prevalence	Accounts for the vast majority of hemophilia cases.	Very rare, with an incidence of about 1.5 cases per million people per year.
Associated Conditions	No underlying conditions needed, though some types may have additional related diagnoses.	Often associated with autoimmune diseases, cancer, pregnancy, or drug reactions.
Typical Symptoms	Prolonged bleeding after injury, surgery, or spontaneously; common joint and muscle bleeds.	Sudden onset of unexplained bleeding, typically in skin, muscles, or soft tissues; joint bleeding is rare.

Types of Inherited Hemophilia and Their Specific Causes

Hemophilia A: The most common form, caused by a genetic mutation resulting in a missing or defective clotting Factor VIII.
Hemophilia B: The second most common type, caused by a genetic mutation leading to a deficiency of clotting Factor IX. It is also known as Christmas disease.
Hemophilia C: A very rare form caused by a mutation in the gene for clotting Factor XI. Unlike types A and B, the F11 gene is located on an autosome (non-sex chromosome), so it can affect both males and females more equally.

Conclusion

The cause of hemophilia is a breakdown in the body's ability to produce or utilize key blood clotting factors, and this can happen in one of two main ways. The vast majority of cases are inherited through an X-linked recessive genetic mutation that affects clotting Factor VIII or IX. The remaining rare cases are acquired later in life due to an autoimmune response where the body’s own antibodies attack clotting factors. Proper diagnosis of the specific type and cause is essential for effective management and treatment. For more information, the National Bleeding Disorders Foundation offers valuable resources on bleeding disorders and their causes.

Visit the National Bleeding Disorders Foundation for more information.

Frequently Asked Questions

The most common cause of hemophilia is an inherited genetic mutation that results in a deficiency or defect in specific clotting factors, primarily Factor VIII or Factor IX.

No, while most cases are inherited, hemophilia can also be acquired later in life. Acquired hemophilia is caused by an autoimmune response where the body's immune system attacks its own clotting factors.

Hemophilia A and B are X-linked recessive disorders. Since males have only one X chromosome, a single mutated copy of the gene is enough to cause the condition. Females have two X chromosomes, so they need a mutation on both to have severe hemophilia, which is very rare.

Yes. About one-third of hemophilia cases are caused by a spontaneous genetic mutation, meaning there is no prior family history of the disorder.

Acquired hemophilia is a rare autoimmune disorder where the immune system attacks and disables a person's own clotting factors, causing abnormal bleeding. It is not inherited and usually occurs in older adults.

Hemophilia A is caused by a deficiency of clotting Factor VIII, while Hemophilia B is caused by a deficiency of clotting Factor IX. Both are inherited in a similar X-linked pattern.

Genetic mutations provide incorrect instructions for making clotting factor proteins. This can result in a missing, defective, or low-level clotting factor, which disrupts the blood's ability to form a proper clot.

Female carriers typically have one normal gene and one mutated gene. In most cases, they do not have severe symptoms, but some may have lower-than-normal factor levels and experience mild bleeding problems.