Coagulation Factor VIII is a blood protein that plays a key role in stopping bleeding. Also known as anti-hemophilic factor (AHF), it is encoded by the F8 gene. This protein is essential for forming blood clots, the body’s natural defense against excessive blood loss after injury. Its proper function is important for maintaining hemostasis, the process that prevents and stops bleeding.
Role in Blood Clotting
Factor VIII functions as a co-factor in the blood coagulation cascade, the process leading to clot formation. In its inactive form, Factor VIII circulates in the bloodstream bound to von Willebrand factor, another plasma protein. Upon injury, Factor VIII activates and separates from von Willebrand factor.
The activated form, Factor VIIIa, works with Factor IXa to activate Factor X. This interaction, requiring calcium ions and phospholipids, forms the tenase complex. The activation of Factor X into Factor Xa is an important step, as Factor Xa then activates prothrombin into thrombin. Thrombin ultimately converts fibrinogen into fibrin, forming the meshwork of a stable blood clot. Factor VIII itself lacks enzymatic activity but significantly increases the rate of Factor X activation by Factor IXa.
When Factor VIII is Deficient
A primary condition linked to insufficient Factor VIII is Hemophilia A, also known as classic hemophilia or Factor VIII deficiency. This inherited genetic disorder involves mutations in the F8 gene, leading to reduced production or an abnormal version of Factor VIII. Hemophilia A follows an X-linked recessive inheritance pattern, meaning males are more frequently and severely affected due to having only one X chromosome. Females have two X chromosomes; if one carries the mutation, the other often provides enough functional Factor VIII to prevent severe symptoms, though they can be carriers and may experience milder bleeding.
About one-third of individuals diagnosed with hemophilia A have no prior family history, occurring due to a new or spontaneous genetic alteration. In addition to the inherited form, a rarer condition is acquired Factor VIII deficiency. This autoimmune disorder involves the body producing antibodies against its own Factor VIII, often presenting with significant hematomas and potentially life-threatening bleeding.
Symptoms of Factor VIII deficiency vary based on the percentage of Factor VIII activity in the blood. Individuals with severe hemophilia A (less than 1% activity) often experience frequent spontaneous bleeding, particularly into joints and muscles. These joint bleeds can cause pain, swelling, and long-term damage. Those with moderate hemophilia A (1% to 5% activity) tend to bleed after injuries, while mild hemophilia A (over 5% activity) may only result in prolonged bleeding after significant injury or surgery. Other common bleeding manifestations include:
Easy bruising
Prolonged bleeding from minor cuts
Nosebleeds that are hard to stop
Blood in urine or stool
Managing Factor VIII Deficiency
Diagnosing Factor VIII deficiency involves specific blood tests, with Factor VIII activity assays being key to confirming the diagnosis and determining severity. While a complete blood count and coagulation studies like prothrombin time are normal, the activated partial thromboplastin time (aPTT) is often prolonged, especially in severe cases. Factor VIII levels are compared to a normal pooled-plasma standard, designated as 100% activity. Specialized tests, such as one-stage and two-stage clotting assays or chromogenic assays, measure the clotting activity of Factor VIII.
Management of Factor VIII deficiency primarily involves replacement therapy, which provides the missing clotting factor. This is achieved through intravenous infusions of concentrated Factor VIII products, derived from human plasma or produced using recombinant DNA technology. These infusions can be given on-demand to treat bleeding episodes or as a prophylactic measure to prevent future bleeds. The goal of prophylaxis is to maintain Factor VIII levels sufficient to reduce bleeding frequency and improve quality of life.
Beyond replacement therapy, other non-factor therapies are available, and gene therapy is emerging as a long-term solution. Gene therapy for hemophilia introduces a functional F8 gene into the patient’s cells, often using a modified virus as a carrier, allowing the body to produce its own Factor VIII. This approach aims to achieve sustained Factor VIII expression and reduce the need for frequent infusions. While gene therapy for hemophilia A is currently offered in clinical trials for severe cases, it represents an important advancement in reducing the treatment burden for affected individuals. Ongoing medical care and a comprehensive treatment plan, often involving a team of specialists, are important for managing Factor VIII deficiency effectively.