What Is Hemophilia? Symptoms, Causes, Diagnosis, and Treatment

Hemophilia is a disorder in which a person’s blood does not clot normally, which can lead to spontaneous or excessive bleeding, according to the Centers for Disease Control and Prevention (CDC). (1)

Blood contains proteins called clotting factors, which can help to stop bleeding. People with hemophilia have lower-than-normal levels of certain clotting factors, which can make bleeding more likely to occur.

Hemophilia is a genetic disorder that can manifest later in life — usually in middle-aged or older people or women who have just given birth or are in the final months of pregnancy.

Hemophilia is rare and it mostly affects males, occurring in about 1 of every 5,000 male births. It can be mild, moderate, or severe, depending on how much clotting factor is in the blood. (1)

Types of Hemophilia

Hemophilia A (Classic Hemophilia)

The most common type of hemophilia, hemophilia A, is caused by an insufficient amount of clotting factor 8.

It is an inherited disorder (passed down from parents to children), but about one-third of cases are caused by a spontaneous gene mutation, or a change in a gene, according to the National Hemophilia Foundation (NHF). (3)

Hemophilia A is much more common in males. It rarely occurs in females.

People with hemophilia A typically bleed for longer periods of time than other people. Two types of bleeding can occur: internal bleeds, which occur in joints and muscles, and external bleeds, from minor cuts, dental procedures, or trauma.

Hemophilia B (Christmas Disease)

Hemophilia B results from insufficient amounts of clotting factor 9. (1)

Like hemophilia A, it’s a genetic disorder, with about one-third of cases caused by a spontaneous mutation. (4) People with hemophilia B bleed for longer periods of time than people who don’t have the disorder. Bleeding can occur internally, in joints and muscles, or externally, from minor cuts, dental procedures, or trauma. Hemophilia B is rare in women.

People with an unusual form of hemophilia B, known as hemophilia B Leyden, have undetectable levels of factor 9 early in life but increasing levels over time. (5) By middle age, they may no longer need treatment for bleeding episodes.

Hemophilia C (Factor 11 Deficiency)

Hemophilia C is caused by a lack of clotting factor 11. (6) Unlike types A and B, spontaneous bleeding or bleeding into joints does not occur unless there is underlying joint disease. A more likely scenario for a person with hemophilia C is extended bleeding after surgery, dental procedures, or trauma. Men and women are equally affected by hemophilia C.

Acquired Hemophilia

While hemophilia is usually an inherited disorder, a rare autoimmune disorder called acquired hemophilia can develop later in life. It happens when your immune system attacks clotting factors in the blood. Scientists believe this can happen as a result of an infection or underlying disorder, and sometimes for no identifiable reason. Acquired hemophilia can occur at any age but is most common among elderly people. It can also be associated with pregnancy, autoimmune conditions, cancer, and multiple sclerosis. (7,8)

Common signs and symptoms of hemophilia include: (1)

• Bleeding into the joints, which can cause swelling and pain or tightness in the joints (often the knees, elbows, and ankles)
• Bleeding into the skin (bruising) or into muscle and soft tissue, causing an accumulation of blood (hematoma)
• Bleeding of the mouth and gums, and bleeding that is difficult to stop after losing a tooth
• Bleeding after circumcision
• Bleeding after having shots or vaccines
• Bleeding in the head of an infant after the baby is delivered
• Blood in the urine or stool
• Frequent bleeding and nosebleeds that are difficult to stop.

RELATED: Learn More About Signs and Symptoms of Hemophilia A

In most cases, hemophilia is a genetic, or inherited, disease.

In hemophilia A and B, the gene for hemophilia is carried on the X chromosome. (3,4) Females inherit two X chromosomes; one from their mother and one from their father. Males inherit an X chromosome from their mother and a Y chromosome from their father. If a son inherits an X chromosome carrying hemophilia from his mother, he will have hemophilia. Fathers can’t pass hemophilia on to their sons (because boys inherit a Y chromosome from their fathers, and hemophilia is X-linked).

Even if females inherit the hemophilia gene from their mother, they are likely to inherit a healthy X chromosome from their father, so they are unlikely to have hemophilia. A daughter who inherits an X chromosome that has a mutation in the gene for hemophilia is called a carrier, and she can pass the gene on to her children. Hemophilia rarely occurs in daughters.

About 30 percent of people with hemophilia have no history of the disorder in their family, but it manifests when an unexpected change occurs in one of the genes associated with hemophilia. (8)

How Hemophilia C Is Inherited

A deficiency in clotting factor 11 is caused by mutations to the F11 gene. (6) It is usually inherited, but in rare instances, new or spontaneous mutations may occur in an individual, causing the disorder.

It’s common for people who have or have had family members with hemophilia to get their baby boys tested for the condition shortly after they’re born. About one-third of babies who have hemophilia have no relatives with the disorder, so infants may be evaluated if they show symptoms. (9)

Ideally, testing is planned before the baby’s birth so that a blood sample can be drawn from the umbilical cord. Umbilical cord blood testing is better at discovering low levels of factor 8 than at finding low levels of factor 9, because factor 9 levels are not at a normal level until a baby is at least 6 months old.

Two types of tests are used for diagnosis: screening tests and clotting factor tests, which are also called factor assays.

Screening Tests

Screening tests are blood tests that reveal whether the blood is clotting properly. There are several types of screening tests for hemophilia:

Complete Blood Count (CBC)

This test measures the amount of hemoglobin (the red pigment inside red blood cells that carries oxygen), the percentage of blood volume occupied by red blood cells (called the hematocrit), the size and amount of red blood cells, and the amounts of white blood cells and platelets in the blood. The CBC is normal in people with hemophilia, but if you have hemophilia and you have unusually heavy bleeding or bleed for a long period of time, the hemoglobin and the hematocrit can be low.

Activated Partial Thromboplastin Time (APTT) Test

This test reveals how much time it takes for blood to clot; specifically, it measures the clotting ability of factors 8, 9, 11, and 12. If any of these clotting factors are diminished, it takes longer than normal for the blood to clot. The results of the APTT test will show a longer clotting time if you have hemophilia A or B.

Prothrombin Time (PT) Test

This test also reveals how long it takes for blood to clot. It focuses on the clotting ability of factors 1, 2, 5, 7, and 10. If any of these factors are in short supply, it takes longer for the blood to clot. Most people with hemophilia A and B will have normal results on this test.

Fibrinogen Test

This test also reveals how well a person can form a blood clot. Fibrinogen is also known as clotting factor 1.

Clotting Factor Tests

Clotting factor tests, which are required to diagnose a bleeding disorder, reveal the type of hemophilia and how severe it is. They check the levels of factor 8 or factor 9 in the blood, and show whether you have mild, moderate, or severe hemophilia.

How Hemophilia C Is Diagnosed

Hemophilia C can be diagnosed via genetic testing.

Prognosis of Hemophilia

People with hemophilia are likely to have a relatively normal life expectancy and quality of life if they receive the treatment that they need and are knowledgeable about their condition. (10)

Some people with hemophilia develop inhibitors, which are antibodies that the immune system creates to attack the clotting factors in hemophilia treatment. (11) This happens when the body mistakes the clotting factors in the treatment for foreign intruders. Inhibitors can negatively affect the course of hemophilia, but new medications are currently being developed. (10)

Around 60 to 70 percent of people with hemophilia A have severe hemophilia, and about 15 percent have moderate hemophilia. (10) The rest have a mild form of the condition.

Acquired hemophilia often goes away with treatment. (11)

There is currently no cure for hemophilia. (13)

The best way to manage hemophilia is often through a comprehensive hemophilia treatment center (HTC). (14) These centers include all the different types of providers — specialists such as hematologists (doctors who specialize in blood) as well as nurses, counselors, and physical therapists — that a person with hemophilia needs.

The primary treatment for hemophilia is replacing the missing clotting factor so the blood can clot properly. (15) The two main replacement therapies are plasma-derived factor concentrates and recombinant factor concentrates. These are both administered through injections.

Plasma-Derived Factor Concentrates

Plasma-derived factor concentrates are blood clotting factors that come from plasma donated by other people. Plasma, the pale-yellowish liquid part of blood, contains blood’s clotting factors. Blood donations are processed to create the freeze-dried factors that go into this therapy.

Recombinant Factor Concentrates

Recombinant factor concentrates are a newer type of therapy that uses genetic engineering to create blood replacement products. This therapy still contains the clotting factors a person with hemophilia needs.

These treatments are both prophylactic (preventive) and therapeutic. That is, they can treat current bleeding and prevent future bleeding incidents.

Medication Options

Other medications people with hemophilia might receive include clot-promoting drugs called antifibrinolytics. The two main antifibrinolytics prescribed to people with hemophilia A are desmopressin acetate (DDAVP) and epsilon-aminocaproic acid.

Alternative and Complementary Therapies

Gene Therapy in Development for Hemophilia A and B

What if, rather than injecting the missing clotting factor into people with hemophilia, you could instead get their bodies to start making it on their own? For more than two decades, scientists have been working on developing a gene therapy for hemophilia that would do just that.

That’s now a reality, with clinical trials reporting successes in gene therapy for both hemophilia A and hemophilia B, (16) and at least two new therapies on track to roll out in late 2022 or early 2023.

Indeed, on November 22, 2022, the U.S. Food and Drug Administration (FDA) approved etranacogene dezaparvovec-drlb (Hemgenix) from CSL Behring as the first gene therapy for hemophilia B. And the very next day, the FDA announced that it was canceling a final review session of BioMarin Pharmaceutical’s valoctocogene roxaparvovec (Roctavian), a gene therapy for severe hemophilia A, which could clear the way for that therapy to launch in early 2023. (The FDA had initially sent valoctocogene roxaparvovec back to BioMarin for further adjustments in August 2020.) (17,26)

RELATED: Learn More About Gene Therapy for Hemophilia A and B

Hypnosis

Hypnosis may also have benefits for hemophilia. In a study from 2019, participants who underwent four weekly hypnosis sessions in addition to their usual treatment had a higher reduction in pain than the control group, and also saw benefits in their quality of life. (18)

RELATED: Learn More About Treatment for Hemophilia: Medication, Alternative and Complementary Therapies, Surgery Options, and More

Prevention of Hemophilia-Related Bleeding Episodes

The NHF’s National Prevention Program recommends that people living with hemophilia “Do the 5” to maintain a healthy lifestyle: (1)

1. Get an annual comprehensive checkup at a hemophilia treatment center.
2. Get vaccinated.
3. Treat bleeds early and adequately.
4. Exercise and maintain a healthy weight to protect your joints.
5. Get tested regularly for blood-borne infections.

RELATED: Learn More About Living Well With Hemophilia A

One of the most serious (but rare) complications of hemophilia is a head injury that causes bleeding in the brain. (8) Symptoms include double vision; painful, long-lasting headache; repeated vomiting; sleepiness; seizures or convulsions; and sudden weakness or clumsiness.

Another serious, but chronic, complication with hemophilia is the development of inhibitors, which make it more difficult to stop a bleeding episode and can increase your risk of death. About 1 in 5 people with hemophilia A develop inhibitors, though scientists still do not fully understand who will get them and why. (19) In hemophilia B, the development of inhibitors is much less common, according to a study from 2018.(20) In hemophilia C, inhibitors can develop, but it’s unclear how often it happens. (6)

It’s important that people with hemophilia who use clotting factor concentrates get a blood test for inhibitors at least once a year. (19) If you’re eligible, you can receive free inhibitor testing at federally funded hemophilia treatment centers provide through the Community Counts Registry for Bleeding Disorders Surveillance program.

RELATED: Learn More About the Complications of Hemophilia: How It Affects Your Body in the Short and Long Term

Hemophilia is rare and predominantly affects males; females are rarely born with the disorder. It can affect people of any race or nationality. (2)

Hemophilia A, the most common type of hemophilia, affects 1 in 5,000 male births. About 400 babies are born with hemophilia A each year, per the CDC. (21)

Hemophilia A accounts for 80 percent of hemophilia cases, or more than 400,000 males worldwide. (22)

Hemophilia B is less common, affecting 1 in 25,000 to 30,000 males. (10)

Hemophilia C is rare in the United States, affecting about 1 in every 100,000 people. Among Ashkenazi Jews from Israel, the prevalence is as high as 8 percent. (6)

Von Willebrand disease

Von Willebrand disease (VWD), the most common bleeding disorder, is an inherited disorder caused by missing or defective von Willebrand factor (VWF), a blood clotting protein, according to the NHF. (23)

VWD affects up to 1 percent of the U.S. population. It is carried on chromosome 12 and occurs in males and females at the same rate.

While people of every race and ethnicity can get hemophilia, there are some challenges that are unique to certain populations. Some studies have found that being Black or Hispanic may possibly play a role in increasing the risk of inhibitor development among people with hemophilia. (19)

A study from 2015 found that nonwhite young adults with moderate or severe hemophilia were more than 5 times as likely as whites to report high levels of chronic pain. (24) These greater levels of chronic pain led to worse overall physical quality of life, bodily pain, physical and social functioning, and greater role limitations due to physical health.

Bleeding Disorders and Black Communities, a private online community hosted by HealthUnlocked, a U.K.-based social health website, aims to provide community and education for Black individuals with bleeding disorders, notes the NHF. (25) Interested participants can request access via this NHF survey.

Centers for Disease Control and Prevention (CDC)

The CDC’s page on hemophilia has links to articles, videos, patient stories, and the Community Counts project to gather data about Americans living with bleeding disorders.

Mayo Clinic

Mayo Clinic is a trusted resource for health and medical information, including information about hemophilia.

National Hemophilia Foundation (NHF)

The NHF is dedicated to finding better treatments and a cure for inheritable bleeding disorders. It does this through awarding research grants and through political advocacy at all levels of government. It also offers opportunities for community education and support through its local chapters, and has a camp locator for children with bleeding disorders.

World Federation of Hemophilia (WFH)

Located in Montreal and working globally, the WFH’s mission is “to close the gap in care between those who receive proper treatment and those who do not.” It works toward this goal by supporting programs around the world to improve medical care for those with bleeding disorders and make treatment products more accessible.