Factor VII (FVII) is a plasma protein and a member of the coagulation factor family, involved in hemostasis, or stopping bleeding. It is a serine protease enzyme that facilitates the breakdown of proteins, a necessary action for the cascade of events leading to clot formation. FVII is continuously produced by the body and plays a specialized role in ensuring blood remains fluid until a vessel injury occurs. When activated, it serves as an immediate trigger for the body’s rapid response system to prevent blood loss.
The Role of Factor VII in Blood Clotting
Factor VII initiates the coagulation cascade through the extrinsic pathway, which is the body’s swift, localized response to trauma and tissue damage. FVII circulates in an inactive form but rapidly activates upon encountering a protein called tissue factor (TF).
TF is an integral membrane protein typically found outside of blood vessels. When a blood vessel wall is breached, underlying cells expose TF to the bloodstream, which acts as a receptor for FVII. The binding of FVII to exposed TF instantly converts the inactive FVII into its active form, Factor VIIa (FVIIa).
The resulting FVIIa-TF complex is the most potent initiator of the entire clotting process. This complex acts as an enzyme, converting two other inactive clotting factors, Factor IX and Factor X, into their active forms, Factor IXa and Factor Xa. The activation of Factor X is particularly significant because it merges the extrinsic pathway into the common pathway of coagulation, leading directly to the formation of thrombin and the final fibrin clot.
This mechanism ensures that clotting is rapid and highly localized, starting only at the precise site of injury where tissue factor has been exposed. FVII is regarded as the “on switch” for the coagulation system, providing the initial burst of activity necessary to form a temporary plug quickly. Its short half-life in the bloodstream (approximately three to six hours) means the initiating signal is quickly downregulated, helping to control the spread of the clot.
Regulation and Production of Factor VII
Factor VII synthesis occurs almost exclusively within the liver, where it is produced as an inactive single-chain molecule. FVII, along with several other coagulation factors, belongs to the group of Vitamin K-dependent proteins, meaning Vitamin K is required for the protein to become biologically functional.
Vitamin K acts as a cofactor for the enzyme gamma-glutamyl carboxylase, which chemically modifies FVII. This modification involves adding a carboxyl group to specific amino acid residues, a step necessary for FVII to properly bind calcium ions. Without this calcium-binding ability, FVII cannot correctly interact with tissue factor and cell surfaces at the injury site, rendering the protein ineffective.
Interference with Vitamin K metabolism directly impacts FVII function. Medications like warfarin, a common blood thinner, block the recycling of Vitamin K, preventing the proper carboxylation and activation of FVII and the other dependent factors. FVII has the shortest half-life among these factors and is the first to show reduced activity when Vitamin K availability is low.
Consequences of Factor VII Deficiency
A deficiency in Factor VII leads to a bleeding disorder because the initial trigger for the coagulation cascade is weakened or absent. This condition is categorized as either inherited (a rare autosomal recessive genetic disorder) or acquired, with varying degrees of severity.
The clinical presentation of low FVII levels is highly variable, ranging from asymptomatic individuals to those who experience severe, life-threatening hemorrhages.
Symptoms of Deficiency
Common, less severe symptoms include frequent nosebleeds, easy bruising, and prolonged bleeding from minor cuts or dental procedures. Women with the condition often experience menorrhagia (heavy and long menstrual bleeding).
More severe presentations involve spontaneous bleeding into muscles, joints, or the gastrointestinal tract. In the most serious cases, particularly in newborns with severe deficiency, intracranial hemorrhage (bleeding into the brain) can occur.
Acquired FVII deficiency is more common and often develops due to underlying medical conditions. These include severe liver disease, which impairs protein synthesis, severe nutritional deficiency of Vitamin K, or as a side effect of anticoagulant therapy.
Therapeutic Use of Activated Factor VII
The pharmaceutical application of Factor VII involves a synthetic version called recombinant activated Factor VII, or rFVIIa. This product is used to treat patients with congenital FVII deficiency, effectively replacing the missing protein to restore normal clotting function.
The most widespread therapeutic use of rFVIIa is as a “bypass agent” for patients with severe hemophilia. Hemophilia A and B are bleeding disorders characterized by deficiencies in Factor VIII and Factor IX. A significant number of these patients develop inhibitors (antibodies) that neutralize standard replacement factors.
When conventional factor replacement therapy is ineffective, rFVIIa is administered to bypass the blocked pathway. The drug works by activating the coagulation cascade further down the line, independent of the inhibited factors. When administered at high concentrations, rFVIIa directly activates Factor X on the surface of activated platelets at the site of a bleed. This high-dose approach skips the initial steps involving Factor VIII and Factor IX, generating a burst of thrombin to form a stable clot and control the hemorrhage.