Hemophilia A, also called factor VIII (8) deficiency or classic hemophilia, is a genetic disorder caused by missing or defective factor VIII (FVIII), a clotting protein. Although it is passed down from parents to children, about 1/3 of cases found have no previous family history.
According to the US Centers for Disease Control and Prevention (CDC), hemophilia occurs in approximately 1 in 5,617 live male births. There are between 30,000 – 33,000 males with hemophilia in the US*. More than half of people diagnosed with hemophilia A have the severe form. Hemophilia A is four times as common as hemophilia B. Hemophilia affects all races and ethnic groups.
The Genetics of Hemophilia
Hemophilia A is an inheritable disease, meaning it is passed down from parents to children. The X and Y chromosomes are called sex chromosomes. The gene for hemophilia is carried on the X chromosome. Hemophilia is inherited in an X-linked recessive manner. Females inherit two X chromosomes, one from their mother and one from their father (XX). Males inherit an X chromosome from their mother and a Y chromosome from their father (XY). That means if a son inherits an X chromosome carrying hemophilia from his mother, he will have hemophilia. It also means that fathers cannot pass hemophilia on to their sons.
But because daughters have two X chromosomes, even if they inherit the hemophilia gene from their mother, most likely they will inherit a healthy X chromosome from their father and not have hemophilia. A daughter who inherits an X chromosome that contains the gene for hemophilia is called a carrier. She can pass the gene on to her children. Many women who carry the hemophilia gene also have low factor expression, which can result in heavy menstrual bleeding, easy bruising, and joint bleeds. Some women who have the hemophilia gene have factor expression low enough to be diagnosed with hemophilia.
For a female carrier, there are four possible outcomes for each pregnancy:
- A girl who is not a carrier
- A girl who is a carrier
- A boy without hemophilia
- A boy with hemophilia
(percentage breakdown of overall hemophilia population by severity)
Severe (factor levels less than 1%) represent approximately 60% of cases
Moderate (factor levels of 1-5%) represent approximately 15% of cases
Mild (factor levels of 6%-30%) represent approximately 25% of cases
What are the Symptoms of Hemophilia A?
People with hemophilia A bleed longer than other people. Bleeds can occur internally, into joints and muscles, or externally, from minor cuts, dental procedures, or injuries. How often a person bleeds and the severity of those bleeds depends on how much FVIII a person produces naturally.
Normal levels of FVIII range from 50% to 150%. Levels below 50% – or half of what is needed to form a clot – determine a person’s symptoms.
• Mild hemophilia A: 6% up to 49% of FVIII in the blood. People with mild hemophilia A generally experience bleeding typically only after serious injury, trauma, or surgery. In many cases, mild hemophilia is not diagnosed until an injury, surgery or tooth extraction results in prolonged bleeding. The first episode may not occur until adulthood. Women with mild hemophilia often experience heavy menstrual bleeding, and can hemorrhage (bleed extensively) after childbirth.
• Moderate hemophilia A: 1% up to 5% of FVIII in the blood. People with moderate hemophilia A tend to have bleeding episodes after injuries.
• Severe hemophilia A. <1% of FVIII in the blood. People with severe hemophilia A experience bleeding following an injury and may have frequent spontaneous bleeding episodes – bleeds that occur without obvious cause – often into their joints and muscles. Many males with severe hemophilia are diagnosed due to bleeding after circumcision.
Diagnosis of Hemophilia A
Doctors will perform tests that evaluate how long it takes for the blood to clot to determine if someone has hemophilia. A clotting factor test, called an assay, will show the type of hemophilia and the severity, or how much clotting factor the person produces on their own.
Most people who have a family history of hemophilia will ask that their baby boys be tested soon after birth to see if they have hemophilia. If there is no family history of hemophilia, people often notice bleeding that takes longer to stop or lots of bruising. Many babies born with severe hemophilia are diagnosed if there is prolonged bleeding after circumcision.
For girls, it often takes seeing worsening of symptoms for the diagnosis process to begin. Most girls are not tested for hemophilia before puberty. Heavy periods are a symptom of a bleeding disorder in women and girls. If there is a known family history, it is important to monitor for symptoms. It is recommended that women who have a family history of hemophilia get tested before getting pregnant, to help prevent complications during childbirth.
The best place for patients with hemophilia to be diagnosed and treated is at one of the federally funded hemophilia treatment centers (HTCs) that are spread throughout the country. HTCs provide comprehensive care from skilled hematologists and other professional staff, including nurses, physical therapists, social workers and sometimes dentists, dieticians and other healthcare providers, including specialized labs for more accurate lab testing.
How is Hemophilia A Treated?
Most treatments for hemophilia A focus on replacing the missing protein, FVIII (8), so a person can form a clot, and so reduce or eliminate the bleeds associated with the disorder. Treatments that work to prevent bleeding through new mechanisms have recently come to the market or are in clinical trials. People with hemophilia A have several different medication options for treatment.
The main medication to treat hemophilia A is concentrated FVIII product, called clotting factor or simply factor. There are two types of clotting factor: plasma-derived and recombinant. Plasma-derived factor is made from human plasma. Recombinant factor products are developed in a lab through the use of DNA technology. While plasma-derived FVIII products are still available, approximately 75% of the hemophilia community takes a recombinant FVIII product.
These factor therapies are injected into a vein (called “infusion”) in the arm or hand, or through a port in the chest. The NHF's Medical and Scientific Advisory Council (MASAC) encourages the use of recombinant clotting factor products over plasma-derived because they are safer from blood-borne viruses and diseases.
To maintain enough clotting factor in the bloodstream to prevent bleeds, patients with severe hemophilia are typically prescribed a regular treatment regimen, called prophylaxis – or prophy for short. This means a person will infuse their medication on a regular schedule – for example every day or every other day, depending on how long the factor lasts in the body. MASAC recommends prophylaxis as optimal therapy for all people with severe hemophilia A.
New treatments that use other ways of preventing bleeds are also available. These treatments are known as non-factor replacement therapies. One available therapy is emicizumab, a laboratory-engineered protein that works by performing a key function in the clotting cascade that is normally carried out by the FVIII protein. It can be prescribed for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children of all ages, newborn and older, with hemophilia A with and without factor VIII inhibitors. Emicizumab is not infused, but injected under the skin (subcutaneously.)
It is important to discuss all treatment options with your doctor or the staff at your HTC.
DDAVP (desmopressin acetate) is the synthetic version of vasopressin, a natural antidiuretic hormone that helps stop bleeding. In patients with mild hemophilia, it can be used for joint and muscle bleeds, for nose and mouth bleeds, and before and after surgery. It comes in an injectable form and a nasal spray. The manufacturer of DDAVP nasal spray issued a recall of all US products and does not expect to begin resupplying until 2022.
Aminocaproic acid prevents the breakdown of blood clots. It is often recommended before dental procedures, and to treat nose and mouth bleeds. It is taken orally, as a tablet or liquid. MASAC recommends that a dose of clotting factor be taken first to form a clot, then aminocaproic acid, to preserve the clot and keep it from being broken down prematurely.
The Future of Hemophilia A Treatment
There are many new treatments for hemophilia A being developed, from gene therapy to new non-factor replacement therapies. Visit the Future Therapies section for updated information on the pipeline of new therapies, as well as extensive information on the development of gene therapy as a treatment for hemophilia.
Living with Hemophilia A
There's a lot to know about living with a bleeding disorder like hemophilia A. Visit NHF’s Steps for Living to explore resources, tools, tips and videos on living with hemophilia A through all life stages. Organized by life stages, Steps for Living provides information on recognizing the signs of bleeds in children, help on navigating school issues, how to exercise safely, helping teens manage their bleeding disorder, information on workplace accommodations, and much more. There are downloadable checklists, toolkits, videos, and more.
Copyright National Hemophilia Foundation
Last Updated January 2022