What is Factor VIII (8)?
Factor 8 (VIII) is a specialized protein called a coagulation, or clotting, factor. People who have a deficiency or defect in factor VIII experience excessive bleeding because their blood does not clot properly, a medical condition called hemophilia A. (Hemophilia B, which is even rarer, is caused by a deficiency or defect in another clotting factor called factor IX.)
Hemophilia A and Factor 8
Hemophilia A is a rare inherited bleeding disorder that typically affects males more than females. According to the National Hemophilia Foundation, roughly one in five thousand males are born with the disorder. An estimated twenty thousand people in the United States are currently living with hemophilia A.
Hemophilia A: Inherited or Developed
While most people with hemophilia A are born with the disorder, roughly one third of all cases are caused by spontaneous genetic changes. Females with hemophilia A are usually carriers, meaning that they can pass down the specific mutation to their children, but do not usually have the disorder themselves.
Roughly 20% of carriers however, do have lower levels of factor VIII than normal. This can cause symptoms akin to those of mild hemophilia. In female carriers, symptoms can include vaginal mucosal bleeding, easy bruising and soft tissue bleeds. If factor VIII is low, there is also an increased risk of excessive bleeding following trauma or during surgery.
100% is the Standard Clotting Factor VIII Level
Healthy people who do not have a bleeding disorder usually have 100% of the factors they need to clot normally. (Technically speaking, someone can have between 50-200% of a given clotting factor and still be considered to be within normal ranges per the Hemophilia, von Willebrand Disease & Platelet Disorders Handbook.)
When someone does not have enough, or has a defect in a given clotting factor, their body cannot correct it on its own by manufacturing more.
Mild, Moderate, and Severe Hemophilia A Factor 8 Levels
According to the National Hemophilia Foundation:
• Mild hemophilia is associated with 6% to 50% factor VIII levels.
• Moderate hemophilia is associated with 1% to 5% factor VIII levels.
• Severe hemophilia is associated with less than 1% factor VIII levels.
Severe hemophilia A
People with severe hemophilia typically experience frequent bleeding events, including bleeding into soft tissues such as muscles, or joints, as often as one to twice per week or more, with or without, an obvious cause or injury. People with severe hemophilia can also develop significant joint damage due to frequent bleeds involving joints. While damage tends to accumulate over time, it can be somewhat mitigated by aggressive treatment.
Bleeding Episodes for Severe, Moderate, and Mild Hemophilia
Those with moderate hemophilia typically experience bleeding episodes with even minor injuries. They may experience a bleeding event as often as once a month or more. They may also experience joint problems due to hemarthrosis (bleeding into joint spaces). Mild hemophilia, on the other hand, rarely causes obvious bleeding into joint spaces.
Bleeding episodes are usually related to obvious trauma, surgery, dental work, or injections (shots). Someone can have mild hemophilia and never experience a serious bleeding issue.
Clotting Factor 8 and the Clotting Cascade
When there is damage to a blood vessel the body protects itself from excessive blood loss by triggering a complex response called a clotting cascade. The clotting cascade seals off the blood vessel, first with a soft clot, then a much stronger one called a fibrin clot, which is later reabsorbed by the body when the tissues have been repaired.
Factor VIII is one of 13 clotting (coagulation) factors. (Clotting factors do not occur in numerical sequence; they are named in order of their discovery, not in the order they work in the clotting cascade.)
Factor VIII is primarily produced in the liver and circulates in the bloodstream in a dormant form. In its inactive state, it is bound up tightly with another clotting protein called the von Willebrand factor until activated by an injury to a blood vessel.
When an injury occurs, factor 8 separates from the von Willebrand factor and interacts with a factor called IX (9). The coagulation cascade is not only extremely complicated, it is also interrelated and interdependent.
This means that if it is stalled at any point due to a defect or deficiency in a given factor, the entire clotting process stops; bleeding continues because a stable clot is not formed.
The Clotting Pathways Explained
Clotting can take one of two pathways: the intrinsic (contact activation) or the extrinsic (tissue) pathway. Both pathways, meet at factor 10 where other key interactions including thrombin and fibrin activate other steps in the process.
The intrinsic pathway is activated when a blood vessel is injured, exposing the underlying collagen to platelets circulating in the blood, hence the name contact pathway. The extrinsic pathway, on the other hand, can be activated by injury, inflammation, outside tissue damage, a malignancy or other causes.
Factor Replacement Therapy
The standard treatment for moderate to severe hemophilia is replacement infusion therapy, which replaces the missing or defective with plasma-derived or recombinant factor VIII. Replacement therapy can be administered in response to a bleeding episode or injury, or prophylactically (as a preventative measure) to reduce the chance of a bleed.
Replacement clotting factor though, does not stay in the body until it is used up. If someone requires factor replacement therapy, they may require infusions as much as two to three times per week because the half-life (time it takes for the body to use or eliminate half of a dose) for factor VIII is, on average, 8 to 12 hours. (Some FVIII products have up to a 19-hour half-life.)
Replacement Factor Therapy and Half-Life
The goal of replacement therapy is to raise the percentage of factor VIII in the blood. For example, if someone with hemophilia A is given replacement factor to raise their levels up to 40% at 9 a.m. on Monday, 12 hours later (9 p.m.), the replacement factor will have dropped back to 20%. This number represents half of the percentage the replacement factor had provided. In another 12 hours, it will have dropped by half again.
Taking Factor Replacement Therapy as Directed
If you have hemophilia, you need to make sure to follow the treatment protocols outlined by your (HTC) hemophilia treatment center, or hemophilia healthcare provider.
Used properly, factor replacement therapy can reduce the number or treatments you need, as well as lowering your overall risk of complications and or permanent damage to organs and joints as you age.
Hemophilia A is a challenging, but treatable disorder. Please click here for more information on how ASP Cares is advancing care for people living with hemophilia.
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This content does not represent medical and or legal advice. It is not meant to diagnose or treat any condition. It is not intended as a substitute for the advice of a qualified medical provider.