What does low factor 8 activity mean? A guide to causes and management

According to the CDC, hemophilia A is the most common type of hemophilia and is caused by a deficiency of clotting factor VIII. This critical component of the blood clotting process explains what low factor 8 activity means for your health and bleeding risk.

Quick Summary

Low factor 8 activity indicates a deficiency of a critical blood clotting protein, often pointing to hemophilia A, an inherited bleeding disorder that causes prolonged or spontaneous bleeding, joint damage, and other health issues.

Key Points

• Core Meaning: Low factor 8 activity indicates a deficiency in a vital blood clotting protein, often signifying a bleeding disorder like hemophilia A.

• Main Causes: The most common causes are inherited hemophilia A, acquired hemophilia from autoantibodies, and von Willebrand disease.

• Risk of Bleeding: Symptoms range from easy bruising and prolonged bleeding to serious joint and muscle hemorrhages, with severity correlating to the activity level.

• Diagnosis is Key: Accurate diagnosis involves blood tests, including factor VIII assays and mixing studies, and sometimes genetic testing to determine the underlying cause.

• Modern Treatment: Contemporary treatment options include intravenous factor replacement therapy, novel non-factor therapies like emicizumab, and in some cases, gene therapy.

• Improved Prognosis: Thanks to modern therapies and proactive management, people with low factor 8 activity can achieve near-normal life expectancy.

Understanding the Blood Clotting Process

To understand what low factor 8 activity means, it's helpful to first grasp the basic mechanism of blood clotting. When a blood vessel is injured, a complex series of chemical reactions, known as the coagulation cascade, is triggered. In this cascade, various proteins called clotting factors work together to form a stable blood clot and stop the bleeding. Factor VIII (FVIII) is a crucial component of this process. It functions as a co-factor for another clotting factor (factor IX), helping to amplify the signal to produce a stable clot. When factor VIII activity is insufficient, the cascade is disrupted, leading to prolonged or excessive bleeding.

Factor VIII levels are typically measured as a percentage of normal. A normal range is generally considered to be 50% to 150%. A level below 50% indicates a deficiency, and the severity is classified based on how low the activity level is. The lower the level, the more severe the bleeding phenotype, which includes the onset, frequency, and severity of bleeding episodes. Modern medicine, including prophylactic treatments, has significantly improved the prognosis and life expectancy for individuals with factor VIII deficiency.

Primary Causes of Low Factor 8 Activity

Low factor 8 activity is not a condition in itself but rather a symptom of an underlying issue. The most common causes are:

• Hemophilia A (Congenital): This is the most widely known cause and is an inherited X-linked recessive disorder, primarily affecting males. It is caused by genetic mutations in the F8 gene that lead to either a dysfunctional factor VIII protein or an insufficient amount of it. Females are typically carriers, but some may have low factor VIII levels and experience bleeding symptoms due to skewed X-chromosome inactivation. Around one-third of hemophilia A cases are caused by new, or de novo, gene mutations.
• Acquired Hemophilia A (AHA): This rare autoimmune disorder occurs when the body's immune system mistakenly produces autoantibodies (called inhibitors) that attack and neutralize factor VIII. Unlike the congenital form, AHA typically emerges in adulthood and affects both men and women equally. It is sometimes associated with pregnancy, autoimmune diseases, cancer, or drug reactions, though often the cause is unknown.
• Von Willebrand Disease (VWD): As the most common inherited bleeding disorder, VWD is caused by a deficiency or defect of von Willebrand factor (VWF). VWF is a protein that serves to bind to and stabilize factor VIII, protecting it from being broken down in the bloodstream. Therefore, defects in VWF can indirectly lead to low factor VIII activity, even if the FVIII gene is normal.
• Disseminated Intravascular Coagulation (DIC): In DIC, the proteins that control blood clotting become abnormally overactive throughout the body. This process consumes clotting factors, including factor VIII, at a rapid pace, leading to widespread bleeding and potentially organ damage.

Signs and Symptoms to Watch For

Recognizing the signs of a factor VIII deficiency is critical for early diagnosis and management. The severity of symptoms often correlates with the level of factor VIII activity.

• Easy or excessive bruising: Bruising can occur from even minor bumps, with large hematomas (buildups of blood under the skin) being common.
• Prolonged or spontaneous bleeding: This can manifest as persistent bleeding from minor cuts, nosebleeds, or internal bleeding without an obvious injury.
• Joint bleeds (hemarthrosis): This is a hallmark symptom, especially in severe cases, where bleeding into the joints can cause pain, swelling, and lead to chronic, debilitating arthritis if untreated.
• Muscle bleeds: Bleeding into the muscles can cause swelling, pain, and potentially permanent nerve damage.
• Intracranial hemorrhage: The most serious and life-threatening complication, where bleeding occurs in or around the brain, even from a minor head injury.
• Heavy menstrual bleeding: For women with low factor VIII activity, heavy and prolonged menstrual periods are a common symptom.

Diagnosing a Factor 8 Deficiency

If a bleeding disorder is suspected based on personal or family history, a healthcare provider will conduct several diagnostic tests.

1. Factor VIII Assay: This blood test directly measures the activity level of factor VIII in the blood. The result, expressed as a percentage, helps determine the severity of the deficiency. For example, severe hemophilia A is defined as having less than 1% activity.
2. Mixing Study: This test is performed when the initial blood test, the activated partial thromboplastin time (APTT), is prolonged. The patient's plasma is mixed with normal plasma. If the APTT corrects, it indicates a factor deficiency. If it doesn't correct, it suggests the presence of an inhibitor (antibody) against factor VIII, pointing toward acquired hemophilia.
3. Von Willebrand Factor (VWF) Assays: Since VWD can cause low factor VIII levels, testing for VWF activity and antigen levels is crucial to differentiate between hemophilia A and VWD.
4. Genetic Testing: Molecular genetic testing can identify the specific mutation in the F8 gene, confirming a diagnosis of inherited hemophilia A and aiding in family counseling.

Treatment Options for Managing the Condition

Treatment for low factor 8 activity depends on the underlying cause and severity.

1. Replacement Therapy: This is the standard treatment for hemophilia A, involving infusing commercially prepared factor VIII concentrates directly into a vein. It can be done on-demand to stop a bleed or as regular prophylactic treatment to prevent bleeding episodes. Recombinant factors (not derived from human plasma) have significantly improved safety by eliminating the risk of transmitting blood-borne viruses.
2. Non-Factor Therapies: Newer treatments, such as the monoclonal antibody emicizumab (Hemlibra®), mimic the function of factor VIII by bringing factors IXa and X together. This provides a non-factor replacement option, administered via a subcutaneous injection, which can be highly effective in reducing bleeding frequency.
3. Desmopressin (DDAVP): For individuals with mild to some moderate cases of hemophilia A or certain types of VWD, DDAVP can be used. It releases stored factor VIII and VWF from the body's tissues, raising their levels to help with clotting.
4. Gene Therapy: A significant advance, gene therapy like Roctavian® involves a one-time intravenous injection to deliver a working copy of the F8 gene to liver cells, enabling the body to produce its own factor VIII. It is currently approved for severe hemophilia A in adult patients.

Comparing Hemophilia A and Von Willebrand Disease

Feature	Hemophilia A	Von Willebrand Disease (VWD)
Cause	Deficiency or defect in clotting factor VIII.	Deficiency or defect in von Willebrand factor (VWF).
Inheritance	X-linked recessive, primarily affecting males.	Autosomal inheritance pattern, affecting both males and females equally.
Symptom Profile	Deep bleeds into joints and muscles are characteristic.	Typically involves mucosal bleeding (nosebleeds, heavy periods), easy bruising, and surgical bleeding.
Prevalence	Approximately 1 in 5,000 male births worldwide.	Most common inherited bleeding disorder, affecting 1% to 3% of the population.

Daily Life with a Factor 8 Disorder

Managing a bleeding disorder effectively allows individuals to lead full and productive lives. This involves a combination of medical treatment and lifestyle adjustments.

• Regular Exercise: Safe physical activity is important for protecting joints and overall health. Your healthcare provider can recommend suitable exercises like swimming, biking, or yoga and advise on necessary precautions, such as infusing factor before a more strenuous activity.
• Good Dental Hygiene: Regular dental care is crucial. Consistent brushing and flossing help prevent gum bleeding and reduce the need for more invasive dental procedures. The World Federation of Hemophilia recommends consistent, thorough oral hygiene practices.
• Home Infusions: Patients on prophylactic therapy can learn to self-administer factor infusions at home, which allows for faster treatment of bleeds and fewer side effects from prolonged bleeding episodes.
• Injury Prevention: Avoiding high-impact sports, wearing protective gear, and taking care to prevent injuries can minimize bleeding risks.

Outlook and Prognosis

With modern diagnosis and treatment, the prognosis for individuals with factor VIII deficiencies has dramatically improved. Life expectancy is now much closer to that of the general population, especially for those receiving prophylactic treatment from a young age. However, complications like joint damage or the development of inhibitors can still occur and require careful management. Ongoing research into novel therapies, including gene therapy and other non-factor treatments, promises to further enhance the quality of life for those affected.

Conclusion

In short, a finding of low factor 8 activity means your blood has a reduced ability to clot effectively, putting you at risk for prolonged or spontaneous bleeding. This condition can be inherited as hemophilia A, acquired through an autoimmune response, or linked to another disorder like von Willebrand disease. A prompt diagnosis via a combination of blood and genetic tests is essential for starting the correct treatment, which may include factor replacement therapy, non-factor therapies, or gene therapy. With proper medical management and lifestyle adjustments, individuals with this condition can lead healthy and active lives.

For more detailed information on living with this condition, you can refer to the Centers for Disease Control and Prevention's guide on hemophilia.

Frequently Asked Questions

What is the normal range for factor VIII activity?

The normal range for factor VIII activity is typically 50% to 150%. A level below 50% is considered deficient and can lead to bleeding problems.

What is the difference between inherited and acquired low factor 8 activity?

Inherited low factor 8 activity is known as hemophilia A, caused by a genetic mutation in the F8 gene and passed down through families. Acquired low factor 8 activity is a rare autoimmune disorder where the body develops antibodies that attack factor VIII, typically in adulthood.

Can females have low factor 8 activity?

Yes. While hemophilia A primarily affects males, females who are carriers can have low factor VIII levels and experience bleeding symptoms. This is sometimes due to a process called skewed X-inactivation.

How are mild, moderate, and severe hemophilia A classified?

The classification depends on the percentage of factor VIII activity. Severe is less than 1%, moderate is 1% to 5%, and mild is greater than 5% to less than 40%.

What are inhibitors in the context of low factor 8 activity?

Inhibitors are antibodies that the body's immune system produces to attack and neutralize factor VIII, making replacement therapy less effective. They are the cause of acquired hemophilia A.

Is low factor 8 activity related to von Willebrand disease?

Yes. Von Willebrand factor helps protect factor VIII from being broken down in the blood. Therefore, a defect or deficiency in von Willebrand factor can indirectly cause low factor VIII activity, even if factor VIII itself is normal.

What is prophylactic treatment for low factor 8 activity?

Prophylactic treatment involves regular, scheduled infusions of factor VIII to maintain clotting factor levels and prevent bleeding episodes from occurring, especially for individuals with severe hemophilia A.