Factor VII is a protein found in the blood that plays a role in blood clotting. It is one of several coagulation factors that work together to form a stable blood clot and stop bleeding following an injury. This protein is produced in the liver and its activity depends on vitamin K. Factor VII is crucial for hemostasis, the body’s natural response to prevent blood loss.
Factor VII’s Role in Blood Clotting
Factor VII holds a key role within the coagulation cascade, initiating the extrinsic pathway. When a blood vessel is injured, tissue factor (TF), a protein normally found outside blood vessels, becomes exposed to the bloodstream. Circulating Factor VII binds to this exposed tissue factor, forming a complex that activates Factor VII to its active form, Factor VIIa.
The Factor VIIa-tissue factor complex activates Factor X into Factor Xa. This activation of Factor X is a key step, as Factor Xa leads to the conversion of prothrombin into thrombin. Thrombin is an enzyme that transforms fibrinogen into fibrin strands, essential for forming the meshwork of a blood clot. This process initiates clotting rapidly at the site of injury.
The extrinsic pathway, initiated by Factor VII and tissue factor, generates activated Factor X. While the primary mechanism involves tissue factor, high concentrations of Factor VIIa can also activate Factor X independently. This dual action highlights Factor VII’s role in forming a hemostatic plug to control bleeding.
Conditions Linked to Factor VII Imbalance
Imbalances in Factor VII levels or activity can lead to health issues. Factor VII deficiency, also known as Alexander’s disease or proconvertin deficiency, is a rare inherited blood disorder where the body produces insufficient or non-functional Factor VII. This condition is typically inherited in an autosomal recessive manner, meaning an individual must inherit a defective gene from both parents. It is the most common of the rare congenital coagulation disorders, affecting approximately 1 in 300,000 to 500,000 people worldwide.
Symptoms of Factor VII deficiency vary from mild to severe, with some individuals experiencing no bleeding problems. Common signs include easy bruising, frequent nosebleeds (epistaxis), bleeding gums, and prolonged bleeding after minor injuries, dental procedures, or surgery. Women with the condition often experience heavy or prolonged menstrual bleeding (menorrhagia). More severe, though less frequent, manifestations can involve bleeding into joints (hemarthrosis), muscles, or life-threatening internal bleeds such as intracranial hemorrhage or gastrointestinal bleeding.
While deficiency is the more common concern, elevated levels of Factor VII activity are also associated with health risks. Higher Factor VII activity has been linked to an increased risk of arterial thrombosis (clot formation in arteries). Elevated Factor VII levels are also associated with an increased risk of venous thromboembolism (VTE). These elevated levels can be influenced by genetic variations or environmental factors such as obesity and estrogen therapy.
Therapeutic Applications of Factor VII
Recombinant Factor VIIa (rFVIIa), often known by brand names like NovoSeven, is a therapeutic application of Factor VII. This manufactured form of activated Factor VII treats bleeding episodes and prevents bleeding during surgical procedures in certain patient populations. It was initially developed for patients with hemophilia A or B who have developed inhibitors, antibodies that make standard clotting factor replacement therapies ineffective.
Recombinant Factor VIIa works by activating Factor X directly, bypassing the need for Factor VIII or Factor IX. This mechanism enables clot formation at the site of bleeding, even when natural clotting factors are reduced or not functioning properly. Beyond hemophilia with inhibitors, rFVIIa also manages severe bleeding in individuals with congenital Factor VII deficiency and in non-hemophiliac patients experiencing uncontrollable hemorrhage due to trauma, surgery, or other conditions. Its ability to promote hemostasis in diverse bleeding scenarios highlights its role as a hemostatic agent.
Living with Factor VII-Related Conditions
Diagnosing Factor VII deficiency involves blood tests assessing clotting ability and Factor VII levels. A prothrombin time (PT/INR) test, which measures how quickly blood clots, shows a prolonged clotting time in individuals with Factor VII deficiency. A specific Factor VII assay confirms the diagnosis by measuring the amount and function of Factor VII protein. For severe cases, diagnosis may occur shortly after birth due to bleeding from the umbilical cord or after circumcision.
Management strategies for Factor VII deficiency vary based on the severity and frequency of bleeding. For mild bleeding, local pressure or antifibrinolytic agents may be sufficient. For more significant bleeding episodes or surgical interventions, Factor VII replacement therapy is often necessary. Options include fresh frozen plasma (FFP), which contains Factor VII and other clotting factors, or Factor VII concentrates. However, FFP has drawbacks like fluid overload risk due to large volumes and Factor VII’s short half-life, necessitating frequent dosing.
Recombinant Factor VIIa (rFVIIa) is an accepted therapeutic option for inherited Factor VII deficiency, used for both spontaneous bleeding and in surgical settings. Its use is often preferred due to its efficacy and the absence of risks associated with blood-derived products. The dosage and frequency of treatment depend on the individual’s Factor VII levels, the type and severity of bleeding, and whether it’s for acute treatment or prophylaxis. Regular monitoring and collaboration with a hematologist are important for individuals living with Factor VII-related conditions to optimize management and prevent complications.