Protein C is a specialized protein produced in the liver that regulates the body’s blood clotting system, known as the coagulation cascade. It is classified as a vitamin K-dependent plasma protein, meaning its synthesis requires Vitamin K. Protein C circulates in the bloodstream as an inactive precursor, waiting for a signal that clotting has occurred and now needs to be controlled. Its primary function is to provide a necessary biological brake to prevent the clotting process from becoming excessive or widespread throughout the body.
How Protein C Regulates Blood Flow
Protein C acts as a powerful natural anticoagulant, ensuring that blood clots form only where needed. It circulates as an inactive enzyme until it encounters a specific complex on the inner lining of blood vessels, the endothelium. This activation is initiated when the clot-forming enzyme, thrombin, binds to a receptor called thrombomodulin on the endothelial surface.
The binding of thrombin to thrombomodulin dramatically changes thrombin’s function from a pro-coagulant to a catalyst that activates Protein C, turning it into Activated Protein C (APC). This newly formed APC then works with its cofactor, Protein S, to neutralize key components of the clotting machinery. Specifically, APC targets and breaks down two activated coagulation factors, Factor V (Va) and Factor VIII (VIIIa), through a process called proteolysis.
Factors V and VIII are cofactors that significantly amplify the production of thrombin, accelerating clot formation. By inactivating Factors Va and VIIIa, APC dismantles the core complex responsible for mass production of the clot-forming enzyme. This mechanism prevents the coagulation cascade from running unchecked, maintaining blood fluidity and preventing widespread clot formation.
Causes and Risks of Protein C Deficiency
When the body has insufficient levels or activity of Protein C, the natural anticoagulant brake fails, leading to an increased and often life-long risk of blood clots. This condition is broadly categorized into two main types: hereditary and acquired deficiency. Hereditary Protein C deficiency results from a mutation in the PROC gene, which provides the instructions for making the protein.
Individuals who inherit a single copy of the mutated gene typically have a mild deficiency, which increases their risk for venous thromboembolism (VTE). VTE includes deep vein thrombosis (DVT) and pulmonary embolism (PE). In rare, severe cases where an infant inherits two mutated copies of the gene, a life-threatening condition called purpura fulminans can develop shortly after birth, characterized by rapid, widespread clotting and tissue death.
Acquired Protein C deficiency is not genetic but develops due to underlying medical conditions or treatments. Severe liver disease or failure can significantly reduce production since the protein is made in the liver. Other causes include severe bacterial infections, Vitamin K deficiency, and the initiation of certain blood-thinning medications like Warfarin.
Testing and Treatment Approaches
Protein C levels are measured through a blood test, often ordered after an unexplained clotting event or if there is a strong family history of thrombosis. The most common method is a functional assay, which determines the actual activity of the protein. This test reveals if the protein is non-functional (Type II deficiency) or deficient in amount (Type I deficiency).
Management of diagnosed Protein C deficiency focuses primarily on preventing dangerous blood clots. For most people with hereditary deficiency who experience a thrombotic event, the standard long-term treatment involves anticoagulation therapy, often with medications like Warfarin or direct oral anticoagulants (DOACs). These medications help restore the balance between clot formation and breakdown, reducing the risk of recurrence.
In acute, severe cases, such as neonatal purpura fulminans or a severe thrombotic event, more aggressive intervention is necessary. This involves the immediate replacement of the missing protein using concentrated Protein C products or fresh frozen plasma. This replacement therapy rapidly restores the anticoagulant balance, which can be lifesaving in critical situations.