Factor VIII Deficiency (Hemophilia A)

Factor VIII deficiency, also known as hemophilia A, is an inherited bleeding disorder that prevents blood from clotting properly. This condition causes prolonged and excessive bleeding either spontaneously or after injuries, making everyday activities and medical procedures potentially dangerous without proper treatment.

Table of contents

• What Is Factor VIII Deficiency?
• Other Names for This Condition
• Medical Identification Codes
• How Factor VIII Deficiency Is Inherited
• Signs and Symptoms
• Severity Levels
• How Doctors Diagnose This Condition
• Treatment Options
• Possible Complications
• Living With Factor VIII Deficiency

What Is Factor VIII Deficiency?

Factor VIII deficiency is a hereditary bleeding disorder caused by a lack or deficiency of blood clotting factor VIII (a protein that helps blood form clots). Without enough factor VIII, blood cannot clot properly to control bleeding^[1][3].

This is the most common type of hemophilia and the most common severe bleeding disorder. It occurs in approximately 1 out of every 5,000 male births and accounts for 80% of all hemophilia cases^[9][12]. The condition affects men and women of all ages, though it is much more common in males due to how it is inherited^[2].

When an injury occurs, your body normally creates a blood clot through a process called hemostasis. Factor VIII is a vital protein involved in this process. During clotting, factor VIII works together with other proteins to generate thrombin, which converts to fibrin and forms a mesh around platelets (small cell fragments in blood) at the site of injury. This stabilizes the clot and stops the bleeding^[6]. Without enough factor VIII, your body generates less thrombin, blood cannot clot properly, and excessive bleeding can occur^[6].

Hemophilia A, Classical hemophilia, Hemophilia A congenital, Factor 8 deficiency congenital

Other Names for This Condition

Healthcare providers and medical literature may refer to this condition by several different names. These include hemophilia A, classical hemophilia, factor 8 deficiency, and congenital factor VIII deficiency^[2][9].

Medical Identification Codes

C1845977
C0019069
Not specified in sources

How Factor VIII Deficiency Is Inherited

Factor VIII deficiency is caused by an inherited X-linked recessive trait, with the changed gene located on the X chromosome. A genetic change accounts for approximately 70% of hemophilia A cases. This change affects the F8 gene, which manages clotting factor VIII^[5][3].

Understanding how this inheritance pattern works helps explain why the condition primarily affects males. Females have two X chromosomes, one from each biological parent. Males have one X chromosome from their mother and one Y chromosome from their father^[3][5].

If a woman has a changed factor VIII gene on one of her X chromosomes, she is considered a carrier. This means the changed gene can be passed down to her children. Boys born to such women have a 50% chance of having hemophilia A. Their daughters have a 50% chance of being a carrier. All female children of men with hemophilia carry the changed gene, whereas male children do not^[3].

Because females have two X chromosomes, if the factor VIII gene on one chromosome does not work, the gene on the other chromosome can often do the job of making enough factor VIII. Males have only one X chromosome, so if the factor VIII gene is missing or not working on a boy’s X chromosome, he will have hemophilia A. For this reason, most people with hemophilia A are male^[3].

Approximately 30% of heterozygous females (women who carry one changed gene) have factor VIII clotting activity below 40% and are at risk for bleeding. Additionally, 25% of heterozygous females with normal factor VIII clotting activity report an increased bleeding tendency^[2]. Some female carriers may have mild hemophilia symptoms, like heavy menstrual periods^[5].

In approximately 30% of cases, people with no family history of clotting or coagulation disorders may have a spontaneous gene mutation that causes hemophilia A^[9].

Signs and Symptoms

The bleeding pattern in factor VIII deficiency is variable, ranging from life-threatening bleeds to mild or no bleeding. People with this condition may experience prolonged bleeding as the main symptom. This is often first seen when an infant is circumcised. Other bleeding problems usually show up when the infant starts crawling and walking^[3].

Mild cases may go unnoticed until later in life. Symptoms may first occur after surgery or injury. Internal bleeding may occur anywhere in the body^[3].

Common symptoms include^[3][5]:

• Excessive bleeding that could be a nosebleed you cannot stop. You may bleed more than expected after surgery, being injured, or after a dental procedure
• Bruises that develop easily from everyday accidents, like bumping into a chair. You may develop painful bruises
• Joint pain and swelling from bleeding into joints. The internal bleeding may make joints swell
• Blood in the urine or stool
• Gastrointestinal tract and urinary tract bleeding
• Bleeding that starts without cause (in moderate to severe forms)

Subcutaneous hematomas (collections of blood under the skin) are characteristic of this condition and can be the first indication of the disease^[15].

People with a mild form of this disease often do not have symptoms unless surgery or dental treatment causes bleeding that does not slow down or stop^[5].

Severity Levels

The age of diagnosis and frequency of bleeding episodes are related to the level of factor VIII clotting activity in the blood^[2]. The amount of factor VIII in your blood is called your “factor activity level.” Everyone’s factor levels are different, and they can change over someone’s lifetime. People with lower factor levels have a greater bleed risk, and people with higher factor levels are better protected from bleeds^[6].

Test results for factor VIII levels are usually reported as a percentage of a “normal” result of 100%. Normal ranges for factor VIII levels are 50% to 150%^[7].

Severe hemophilia A (less than 1% factor activity): More than half of people with hemophilia A have this severe form. Individuals are usually diagnosed during the first two years of life following oral or soft tissue bleeding either with procedures or due to a known family history of hemophilia. Without preventive treatment, individuals may average up to two to five spontaneous bleeding episodes each month including spontaneous joint bleeds or deep-muscle hematomas, and prolonged bleeding or excessive pain and swelling from minor injuries, surgery, and tooth extractions^[2].

Moderate hemophilia A (1% to 5% factor activity): Less frequent spontaneous bleeding, although it varies between individuals. Affected individuals have prolonged or delayed bleeding after relatively minor trauma and are usually diagnosed before age five to six years. The frequency of bleeding episodes varies, usually from once a month to once a year^[2].

Mild hemophilia A (5% to less than 40% factor activity): Individuals generally do not have spontaneous bleeding episodes. However, without pre- and postoperative treatment, abnormal bleeding occurs with surgery or tooth extractions. The frequency of bleeding episodes varies widely, typically from once a year to once every ten years. Individuals with mild hemophilia A are often not diagnosed until later in life^[2].

After major trauma or invasive procedures, prolonged or excessive bleeding usually occurs, regardless of severity^[2].

How Doctors Diagnose This Condition

Severe cases of hemophilia are usually diagnosed within the first year of life. Mild forms might not be apparent until adulthood. Some people learn they have hemophilia after they bleed excessively during a surgical procedure^[13].

If you are the first person in your family to have a suspected bleeding disorder, your healthcare provider will order a series of tests called a coagulation study. Once the specific change has been identified, other people in your family will need tests to diagnose the disorder^[3].

A healthcare provider may do several blood tests. Common tests include^[3][5]:

• Complete blood count (CBC) to measure the amount of hemoglobin in your red blood cells, the size and number of your red blood cells, and the number and type of platelets and white blood cells in your blood
• Prothrombin time (PT) test to measure how long it takes blood to clot
• Partial thromboplastin time (PTT) or activated partial thromboplastin time test to measure how long it takes blood to form clots
• Serum factor VIII activity test to measure the clotting activity of factor VIII

Tests called partial thromboplastin time (PTT) and prothrombin time (PT) are usually the first step in hemophilia testing. These tests focus on clotting pathways. Even if you have hemophilia, the results of your PTT and PT tests may be normal, so the blood test for factor VIII is used to confirm the diagnosis^[7].

If your factor VIII activity level is less than 50%, you may have hemophilia A. But how severe your risk of bleeding is depends on what percentage you have^[7].

If you have a family history of hemophilia, genetic testing might be used to identify carriers to make informed decisions about becoming pregnant. It is also possible to determine during pregnancy if the fetus is affected by hemophilia. However, the testing poses some risks to the fetus^[13].

Treatment Options

Healthcare providers cannot cure this disease, but treatments are available to prevent or reduce bleeding^[5]. The main treatment involves replacing the missing clotting factor^[3][10].

Treatment of patients with hemophilia ideally should be provided through a comprehensive hemophilia care center. These centers follow a multidisciplinary approach, with specialists in hematology, orthopedics, dentistry, and surgery; nurses; physiotherapists; social workers; and related allied health professionals. Patients treated at comprehensive care clinics have been shown to have better access to care, less morbidity, and better overall outcome^[4].

The standard way to treat hemophilia A is to replace the missing blood clotting factor so that the blood can clot properly. One way to do this is by infusing (injecting into a vein) commercially prepared clotting factor concentrates. For hemophilia A, another treatment method is a non-factor product that stands in for, or replaces the function of, the missing factor VIII. This treatment is given by injection under the skin that can be given by people with hemophilia themselves^[10].

Types of clotting factor products include^[10]:

• Plasma-derived factor concentrates: Made from human plasma proteins. All blood and parts of blood are routinely tested for viruses. The plasma goes through several processes to separate it into components, such as clotting factors. The clotting proteins are then made into a freeze-dried product, which is tested and treated to kill any potential viruses before it is packaged for use
• Recombinant factor concentrates: Does not come from human plasma. This concentrate is genetically engineered using DNA technology. These factors do not contain any plasma or albumin, and therefore, cannot spread any bloodborne viruses

How much clotting factor you get depends on the severity of bleeding, the site of bleeding, and your weight and height^[3]. Dose calculations are directed toward achieving a factor VIII activity level of 30-40% for most mild hemorrhages, of at least 50% for severe bleeds or major surgery, and 80-100% for life-threatening hemorrhage^[4].

Healthcare providers typically prescribe treatment products for episodic care or prophylactic care. Episodic care is used to stop bleeding episodes; prophylactic care is used to prevent bleeding episodes from occurring^[10].

People with hemophilia can learn how to perform infusions themselves so that they can stop bleeding episodes and, by performing the infusions on a regular basis, can even prevent most bleeding episodes. Giving factor treatment products at home means that bleeds can be treated more quickly, resulting in less serious bleeding and fewer side effects^[10].

Preventive therapy started early in childhood, as compared with on-demand treatment, can reduce total bleeds and bleeding into joints, resulting in decreased overall joint deterioration and improved quality of life^[4].

Other treatment options include^[3][13]:

• Desmopressin (DDAVP): In some forms of mild hemophilia, this hormone can stimulate the body to release more clotting factor. It can be injected slowly into a vein or used as a nasal spray. Mild hemophilia may be treated with desmopressin to help the body release factor VIII that is stored within the lining of blood vessels
• Emicizumab (Hemlibra): A newer drug that does not include clotting factors. This drug can help prevent bleeding episodes in people with hemophilia A
• Clot-preserving medications: Also known as anti-fibrinolytics, these medications help prevent clots from breaking down

Some people who infuse with clotting factor concentrates may develop an inhibitor. Inhibitors are antibodies in the blood that attack and deactivate factor VIII. Inhibitors make it more difficult to stop a bleeding episode because they prevent the treatment from working^[10].

To prevent a bleeding crisis, people with hemophilia and their families can be taught to give factor VIII concentrates at home at the first signs of bleeding. People with severe forms of the disease may need regular preventive treatment^[3].

You should get the hepatitis B vaccine. People with hemophilia are more likely to get hepatitis B because they may receive blood products^[3].

Possible Complications

People with hemophilia A may have an increased risk of several complications^[5]:

• Bleeding into the brain: This is a life-threatening condition. You should get medical care right away if you have symptoms like double vision or a severe headache that does not go away
• Anxiety and depression
• Chronic pain
• Increased risk of heart disease

Without proper treatment, joint bleeds can lead to chronic arthropathy (joint disease) and deformities. Prompt and appropriate treatment of hemorrhage is important to prevent long-term complications and disability^[4].

Living With Factor VIII Deficiency

With treatment, most people with hemophilia A are able to lead a fairly normal life^[3]. Living with hemophilia means more than periodic visits to the doctor and taking regular medication. The condition requires people to take intentional steps in their lives to reduce the risk of complications and live as healthy a life as possible^[22].

Getting high-quality care: Approximately 100 hemophilia treatment centers exist throughout the United States and Canada. These centers let patients receive all their hemophilia-related healthcare in one place. Research has shown that people with hemophilia who receive care at a hemophilia treatment center have better long-term health outcomes^[22].

Physical activity: Regular exercise can help reduce the risk of joint bleeds and improve overall well-being. Physical activity is crucial for maintaining muscle strength and joint health, which are essential for individuals with bleeding disorders. However, it is important to choose activities that are safe and suitable for your condition^[18].

Factor levels can impact lifestyle and activity. You may choose to make lifestyle adjustments or engage in less physical activities to reduce the risk of bleeding and pain associated with hemophilia. The lower a person’s factor VIII activity levels are, the lower their level of physical activity tends to be^[6].

Emergency preparedness: Having the necessary supplies on hand in case of a bleed can significantly reduce stress and provide peace of mind. Put together a hemophilia emergency kit that you can carry with you. It might be helpful to keep a small kit with you at all times and store extra supplies in your car for emergencies^[17].

Diet and nutrition: Diet plays a crucial role in managing bleeding disorders. Maintaining iron levels is particularly important for people with hemophilia. Iron-rich foods include liver, lean red meat, poultry, leafy green vegetables such as spinach, broccoli, dried beans, grains, and raisins^[19].

Medication adherence: Adhering to your medication regimen is vital for managing bleeding disorders effectively. Missing doses can lead to increased risk of bleeding episodes and other complications^[18].

Support and community: You may have hemophilia, but you do not have to face it alone. Connecting with others who share similar experiences can make a world of difference. Both children and adults can benefit from spending time with others who also live with hemophilia, perhaps in an in-person or online support group^[17].

If you are considering dietary supplements, discuss your choices with your doctor before taking any supplements, as some might increase bleeding tendency or clotting times. Some supplements — such as vitamin E, fish oil, gingko biloba, bromelain, flax seed, garlic, or ginger — may need to be avoided altogether^[8].