Protein C Immunologic
Differentiating congenital Type I protein C deficiency from Type II deficiency.
Evaluating the significance of decreased functional protein C, especially when decreased protein C activity might be congenital rather than acquired (eg, due to oral anticoagulant effect, vitamin K deficiency, liver disease, or intravascular coagulation and fibrinolysis/disseminated intravascular coagulation)
Not useful for predicting a thrombotic event.
Protein C is a vitamin K-dependent anticoagulant proenzyme. It is synthesized in the liver and circulates in the plasma. The biological half-life of plasma protein C is approximately 6 to 10 hours, similar to the relatively short half-life of coagulation factor VII.
Protein C is activated by thrombin, in the presence of an endothelial cell cofactor (thrombomodulin), to form the active enzyme, activated protein C (APC). APC functions as an anticoagulant by proteolytically inactivating the activated forms of coagulation factors V and VIII (factors Va and VIIIa). APC also enhances fibrinolysis by inactivating plasminogen activator inhibitor (PAI-1).
Expression of the anticoagulant activity of APC is enhanced by a cofactor, protein S, another vitamin K-dependent plasma protein.
Congenital homozygous protein C deficiency results in a severe thrombotic diathesis, evident in the neonatal period and resembling purpura fulminans. Congenital heterozygous protein C deficiency may predispose to thrombotic events, primarily venous thromboembolism. Arterial thrombosis (stroke, myocardial infarction, etc) may occur. Some individuals with hereditary heterozygous protein C deficiency may have no personal or family history of thrombosis and may or may not be at increased risk.
The 2 types of hereditary heterozygous protein C deficiencies that are recognized are:
-Type I (concordantly decreased protein C function and antigen)
-Type II (decreased protein C function with normal antigen)
Acquired deficiency of protein C may occur in association with:
-Vitamin K deficiency
-Oral anticoagulation with Coumadin compounds
-Intravascular coagulation and fibrinolysis/disseminated intravascular coagulation (ICF/DIC)
Values <70% to 75% may represent a congenital deficiency state, if acquired deficiencies can be excluded.
Protein C antigen and activities generally are undetectable in individuals with severe, homozygous protein C deficiency.
Acquired protein C deficiency is of uncertain clinical hemostatic significance.
Clinical significance of increased protein C is unknown.