What Is Hemophilia? Symptoms, Causes, Diagnosis, and Treatment
Hemophilia is a genetic disorder in which a person’s blood does not clot normally. This can lead to spontaneous or excessive bleeding, according to the Centers for Disease Control and Prevention (CDC).
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 can also show up 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.
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 Bleeding Disorders Foundation (NBDF).
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 others. 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.
Like hemophilia A, it’s a genetic disorder, with about one-third of cases caused by a spontaneous mutation. 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. 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. 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.
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.
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. 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. Symptoms of hemophilia rarely occur in females.
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.
How Hemophilia C Is Inherited
A deficiency in clotting factor 11 is caused by mutations to the F11 gene. 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.
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.
Some people with hemophilia develop inhibitors, which are antibodies that the immune system creates to attack the clotting factors in hemophilia treatment. 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.
Around 60 to 70 percent of people with hemophilia A have severe hemophilia, and about 15 percent have moderate hemophilia. The rest have a mild form of the condition.
Acquired hemophilia often goes away with treatment.
There is currently no cure for hemophilia. However, there are treatments that can help people with the condition live long and happy lives.
The best way to manage hemophilia is often through a comprehensive hemophilia treatment center (HTC). 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 needs without viruses or unwanted proteins from human blood.
The primary treatment for hemophilia is replacing the missing clotting factor so the blood can clot properly. The two main replacement therapies are plasma-derived factor concentrates and recombinant factor concentrates. These are both administered through injections or infusions.
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 concentrate therapy 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.
Increasing Clotting Enzymes
Another form of treatment has been developed that increases the level of clotting enzymes in the blood.
The U.S. Food and Drug Administration (FDA) has approved a new medicine that has been shown to prevent or reduce the number of bleeding episodes. Marstacimab-hncq (Hympavzi) is a medication that lowers the amount of anticoagulation proteins in the body, called tissue factor pathway inhibitors. When the level of these of these proteins is lowered, this allows the body to produce more thrombin, which is the enzyme that causes blood to clot.
Marstacimab-hncq can be used to treat anyone age 12 or older who has hemophilia A without factor 8 inhibitors or hemophilia B without factor 9 inhibitors (neutralizing antibodies). The drug is given weekly through a prefilled auto-injection pen.
Alternative and Complementary Therapies
Gene Therapy for Hemophilia A and B Gene therapy eliminates the need for repeated treatment. With gene therapy, a one-time infusion is given that delivers a working copy of the faulty gene that causes hemophilia. This working gene provides instructions for the body to produce the missing clotting factor.
Gene therapy became available in November 2022 when the FDA approved etranacogene dezaparvovec-drlb (Hemgenix) as the first gene therapy for hemophilia B.
In June 2023, the FDA approved valoctocogene roxaparvovec (Roctavian), a gene therapy for severe hemophilia A.
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.
Prevention of Hemophilia-Related Bleeding Episodes
The NBDF’s T.H.R.I.V.E. Campaign recommends that people living with hemophilia follow these six steps to maintain a healthy lifestyle:
Take advantage of regular care from healthcare providers focusing on bleeding disorders.
Have a conversation with your healthcare provider about yearly inhibitor testing.
Review the latest treatment options for you.
Identify, treat, and fully heal bleeds.
Value and make time for your emotional and mental health.
Embrace your bleeding disorders community and get involved.
One of the most serious (but rare) complications of hemophilia is a head injury that causes bleeding in the brain. 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.
With hemophilia B, the development of inhibitors is much less common, according to a study from 2018.
In hemophilia C, inhibitors can develop, but it’s unclear how often it happens.
It’s important that people with hemophilia who use clotting factor concentrates get a blood test for inhibitors at least once a year. If you’re eligible, you can receive free inhibitor testing at federally funded hemophilia treatment centers provided through the Community Counts Registry for Bleeding Disorders Surveillance program.
Hemophilia is rare and predominantly affects males; females are rarely born with the disorder. It can affect people of any race or nationality.
Hemophilia A, the most common type of hemophilia, affects 1 in 5,000 male births. About 400 babies in the United States are born with hemophilia A each year, per the CDC.
Hemophilia A accounts for 80 percent of hemophilia cases, or more than 400,000 males worldwide.
Hemophilia B is less common, affecting 1 in 25,000 to 30,000 males.
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.
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 NBDF.
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 have 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.
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. 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.
The Takeaway
Hemophilia is a genetic disorder where blood does not clot normally, which may lead to prolonged bleeding episodes. This disease mostly affects males.
There are several different types with the most common being hemophilia A and hemophilia B. Screening tests and genetic testing can be used to diagnose hemophilia.
Hemophilia treatment centers can help you take an overall health approach to managing this disease by providing support and education.
The standard treatment for hemophilia is factor replacement therapy.
Other treatments include gene therapy and medicine that helps raise the level of clotting enzymes in the body.
