Factor VII (FVII) is a vitamin K-dependent protein produced in the liver that plays a role in stopping bleeding. It circulates in the blood plasma as an inactive molecule, or zymogen. FVII is part of the coagulation cascade, a sequence of events that leads to the formation of a stable blood clot. This protein acts as a rapid-response mechanism, ensuring the clotting process is initiated quickly at the site of vascular injury to maintain hemostasis.
The Specific Function of Factor VII in Coagulation
Factor VII is the primary initiator of blood clotting by activating the Tissue Factor Pathway. This process begins the instant a blood vessel is damaged and surrounding cells release Tissue Factor (TF). TF is not normally exposed to circulating blood, but once exposed, it immediately binds to inactive FVII.
This binding converts FVII into its active form, Factor VIIa (FVIIa), creating the enzyme complex known as TF-FVIIa. The TF-FVIIa complex acts as a catalyst, primarily activating Factor X (FX) into Factor Xa (FXa). This step leads into the final common pathway of coagulation, resulting in the production of thrombin and the formation of a fibrin mesh clot. The TF-FVIIa complex also activates Factor IX (FIX) to FIXa, which amplifies the clotting response.
Understanding Factor VII Deficiency
Factor VII deficiency is the most common of the rare, inherited bleeding disorders, affecting an estimated one in 300,000 to 500,000 individuals. The hereditary form is autosomal recessive, meaning an individual must inherit a mutated F7 gene from both parents. Symptom severity is highly variable, often correlating with the amount of functional FVII protein present in the blood.
Symptoms
Symptoms range from mild, such as easy bruising and occasional nosebleeds (epistaxis), to severe, life-threatening hemorrhages. Women frequently experience heavy or prolonged menstrual bleeding (menorrhagia). More severe manifestations include bleeding into joints (hemarthrosis), muscles, the gastrointestinal tract, or the central nervous system.
Acquired Deficiency
The condition can also be acquired later in life due to underlying health issues that interfere with FVII production or function. Acquired forms are associated with severe liver disease, where FVII is synthesized, or with vitamin K deficiency, which is required for the protein’s function. Certain medications, such as blood thinners like warfarin, can also cause an acquired deficiency by inhibiting vitamin K-dependent clotting factors.
Diagnosis and Management
Diagnosis involves blood tests that measure clotting time, particularly the Prothrombin Time (PT) test. A prolonged PT, often with a normal result on the aPTT test, suggests a deficiency in FVII or other extrinsic pathway factors. The diagnosis is confirmed by a specific Factor VII assay, which measures the protein’s level and activity. Management focuses on preventing and controlling bleeding, often requiring therapeutic replacement of the missing factor.
Medical Applications of Recombinant Factor VII
Recombinant activated Factor VII (rFVIIa) is a pharmacological version of the active clotting protein used to control severe bleeding. This synthetic product, often known as NovoSeven, was originally developed to treat patients with hemophilia A or B who developed inhibitors against standard replacement therapies. In these patients, rFVIIa acts as a “bypass agent,” circumventing the blocked part of the coagulation cascade.
When administered intravenously, rFVIIa activates Factor X directly on the surface of activated platelets. This mechanism does not require Factor VIII or Factor IX, making it effective when the standard clotting mechanism is compromised. The medication is also approved for treating bleeding in individuals with congenital FVII deficiency.
rFVIIa is often used in a hospital setting for severe, uncontrolled bleeding related to massive trauma, major surgery, or postpartum hemorrhage. Its use is generally reserved for life-threatening hemorrhages that have not responded to other treatments due to the potential risk of unwanted blood clots (thrombosis) and its high cost.