What to know about hemophilia A

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In most cases, hemophilia is an inherited bleeding disorder. This means that a person inherits gene variations from their parents that affect their ability to produce blood clotting proteins.

Specifically, hemophilia A occurs due to a genetic alteration in the F8 gene, which is present on the X chromosome (one of two chromosomes that determine biological sex). This is why some health experts may refer to hemophilia A as an X-linked condition.

The F8 gene is responsible for producing clotting factor VIII, which is crucial for the blood clotting process. This gene variation results in insufficient levels of factor VIII, which leads to difficulty forming blood clots and causes prolonged bleeding.

Although a person typically inherits hemophilia A from a parent, evidence suggests that roughly 33% of cases occur in individuals with no family history of the condition.

In rare cases, a person may develop acquired hemophilia. This is when hemophilia develops in individuals without a personal or family history of conditions that affect blood clotting. It can occur if the body produces antibodies that mistakenly attack blood clotting factors.

However, in other cases, it may occur without a known cause. A 2021 article suggests that acquired hemophilia A is more complex than initially thought and may have many possible causes.

Hemophilia A is the most common type of hemophilia. However, there are different types of hemophilia. The characteristic feature of each type is the clotting factor they affect.

Hemophilia A occurs due to an alteration in the F8 gene, which causes a deficiency in clotting factor VIII.

Hemophilia B, also known as Christmas disease or factor IX deficiency, affects the F9 gene. As the name suggests, this type of hemophilia results in a low level of clotting factor IX. Hemophilia C, also known as factor XI deficiency, affects the F11 gene and causes a low level of clotting factor XI.

There are also less common conditions that affect other blood clotting factors.

The Centers for Disease Control and Prevention (CDC) note that hemophilia occurs in roughly 1 of every 5,000 male births. Approximately 400 males are born with hemophilia A each year. Hemophilia can also affect females, but this is much rarer.

The condition affects people from all racial and ethnic groups.

Most people with hemophilia A are born with it. In most cases, they inherit the condition from a parent. The genes for clotting factors, such as the F8 gene, are present on the X chromosome. A male will typically inherit one X chromosome from their female parent, while females will typically inherit an X chromosome from both their male and female parents.

This is why hemophilia A is more common in males, as they typically only require one gene variation to develop the condition. For hemophilia A to develop in females, they will either require two X chromosomes with a gene alteration or one variation and the other X chromosome to be missing or nonfunctional.

Read on to learn more about hemophilia inheritance patterns.

The characteristic feature of hemophilia A is a deficiency in the factor VIII clotting protein. The severity of symptoms will relate to the amount of clotting factor a person has in their blood. The symptoms of hemophilia A are typically as follows:

Severe hemophilia A

This typically describes a person with less than 1% clotting activity. Symptoms may include:

• frequent and spontaneous joint and muscle bleeding
• hemophilic arthropathy (irreversible joint damage), which can cause physical disability
• prolonged bleeding or excessive pain and swelling after minor injuries or surgery
• frequent nosebleeds
• bruising easily

Moderate hemophilia A

People with moderate hemophilia A typically have between 1–5% clotting factor activity. Symptoms may include:

• occasional spontaneous bleeding
• prolonged bleeding with more significant injuries or surgery
• occasional nosebleeds
• bruising easily

Mild hemophilia A

Mild hemophilia A typically describes factor activity between 5–40%. Symptoms can include:

• infrequent or no spontaneous bleeding
• bleeding typically occuring only after injuries, trauma, or surgery
• symptoms potentially not manifesting until later in life

In most cases, severe hemophilia A manifests in early life, while mild or moderate hemophilia A will present later in childhood or adolescence. As such, many people with hemophilia A may receive a diagnosis shortly after birth.

Diagnosis of hemophilia A may involve blood tests to measure the levels and activity of clotting factors. These can include:

• activated partial thromboplastin time
• prothrombin time
• fibrinogen level
• platelet count
• serum factor VIII activity

As well as providing a diagnosis, these tests can also help assess the severity of hemophilia A by identifying the amount of clotting factor a person has.

Before giving birth, genetic testing and counseling can also help identify whether a person carries a gene variation and how likely it is to pass to children. Genetic testing can also determine the specific gene alteration responsible for the condition.

Excessive bleeding due to hemophilia A can result in complications, especially if it is left untreated. These can include:

• anemia from blood loss
• bleeding in joints that can cause chronic joint disease, pain, and limited mobility
• bleeding in the brain, which can cause long-term problems such as seizures and paralysis
• bleeding in vital organs, which can be fatal

A person with hemophilia may also develop a type of antibody known as an inhibitor. These inhibitors can make it more difficult to treat a bleeding episode, as they can prevent treatments from working.

Treatment for hemophilia A typically involves replacement therapy for the deficient factor VIII. This may involve regular infusions of factor VIII or antibody therapy.

For cases of mild hemophilia A, a person may receive desmopressin for short-term support. This drug can help increase the concentration of factor VIII in the blood. A person may also receive aminocaproic acid or tranexamic acid oral medications to help treat bleeding.

In June 2023, the Food and Drug Administration (FDA) gave approval for a gene therapy treatment for adults with severe hemophilia A. Roctavian uses a modified virus that contains the gene for factor VIII. After a single dose, the virus carries the factor VIII gene into liver cells, which enables the liver to produce factor VIII.

Hemophilia A is a bleeding disorder that occurs due to a deficiency in clotting factor VIII. Most cases occur due to inheriting an alteration in the F8 gene.

Hemophilia A can vary in severity and requires careful management to help prevent severe bleeding episodes and potential complications. Treatment often involves replacing the deficient factor VIII to help with blood clotting and help prevent excessive bleeding.