Protein C is a plasma protein that regulates blood clotting. It is a zymogen, synthesized in the liver and dependent on Vitamin K for activity. Protein C balances preventing excessive bleeding and uncontrolled clotting. Its primary role is to brake the coagulation system, ensuring clotting does not spread once a clot is formed.
The Anticoagulant Mechanism
The anticoagulant action of Protein C begins when it is converted into Activated Protein C (APC). Activation occurs on the surface of endothelial cells. Thrombin binds to the receptor thrombomodulin to form a complex, which efficiently converts inactive Protein C into active APC.
Once formed, APC functions as a serine protease. APC targets and irreversibly inactivates two key pro-coagulant factors: Factor Va and Factor VIIIa. These factors accelerate thrombin production necessary for clot formation. By inactivating them, APC slows down the amplification phase of coagulation.
The effectiveness of APC is enhanced by Protein S, a vitamin K-dependent cofactor. Protein S helps APC bind to cell surfaces where clotting factors are assembled, controlling the extent of clot formation.
Understanding Protein C Deficiency
A deficiency in Protein C disrupts the natural anticoagulant system, leading to thrombophilia, an increased risk for abnormal blood clot formation. This deficiency is categorized as either inherited or acquired.
Inherited deficiency is a genetic condition caused by mutations in the PROC gene, often passed down in an autosomal dominant pattern. One copy results in a mild, heterozygous deficiency; two copies result in a severe, homozygous deficiency.
The primary consequence is an elevated risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE). Heterozygous individuals often remain asymptomatic, but their VTE risk is higher, especially during surgery or prolonged immobilization.
The most severe form is neonatal purpura fulminans, a rare, life-threatening condition. It occurs in newborns with the severe deficiency, causing widespread clotting in small vessels shortly after birth. This leads to skin lesions, tissue death, and rapid consumption of clotting factors.
Acquired deficiency is more common, resulting from medical conditions that impair liver production, such as severe liver disease. It can also be acquired through Vitamin K deficiency, severe systemic infection, or Warfarin initiation.
Diagnosing and Managing Low Protein C Levels
Diagnosis relies on specific laboratory tests performed on a plasma sample. The most common method is a functional assay, which measures the protein’s actual activity. Functional tests detect both quantitative (low amount) and qualitative (poor function) deficiencies. An antigenic assay, measuring the total amount of Protein C present, may also be used.
Management depends on the deficiency’s severity and whether the patient has previously experienced a clot. For mild, heterozygous deficiency without prior clotting, treatment may not be necessary unless clotting risk is significantly increased, such as during surgery.
Patients who have experienced a VTE are managed with long-term anticoagulation therapy to reduce recurrence. Standard treatment involves blood-thinning medications, such as Warfarin or Direct Oral Anticoagulants (DOACs). For acute, severe thrombotic events, especially in newborns with purpura fulminans, a purified Protein C concentrate can be administered to rapidly restore anticoagulant function.