(See also Overview of Thrombotic Disorders Overview of Thrombotic Disorders In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces. Numerous genetic, acquired, and environmental factors can tip... read more .)
Protein C is a vitamin K–dependent protein, as are coagulation factors VII, IX, and X; prothrombin; and proteins S and Z. Because activated protein C (APC) degrades factors Va and VIIIa, APC is a natural plasma anticoagulant. Decreased protein C due to a genetic or an acquired abnormality predisposes to venous thrombosis Deep Venous Thrombosis (DVT) Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more .
Heterozygous deficiency of plasma protein C has a prevalence of 0.2 to 0.5%; about 75% of people with this defect experience a venous thromboembolism (50% by age 50).
Homozygous or doubly heterozygous deficiency causes neonatal purpura fulminans, ie, a severe neonatal type of disseminated intravascular coagulation (DIC), which manifests with ecchymoses and extensive venous and arterial thromboses, usually on the first day of life.
Acquired decreases in protein C occur in patients with liver disease or disseminated intravascular coagulation (DIC) Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation... read more , and during warfarin therapy.
Diagnosis is based on antigenic and functional plasma assays of protein C.
Treatment of Protein C Deficiency
Patients with symptomatic thrombosis require anticoagulation with heparin or low molecular weight heparin, followed by warfarin. Use of the vitamin K antagonist, warfarin, as initial therapy occasionally causes thrombotic skin infarction by lowering vitamin K–dependent protein C levels before a therapeutic decrease has occurred in vitamin K–dependent coagulation factors.
It is probable, but not yet certain, that the direct oral anticoagulant (DOAC) inhibitors Treatment In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces. Numerous genetic, acquired, and environmental factors can tip... read more of either thrombin (dabigatran) or factor Xa (eg, rivaroxaban, apixaban) can be used in place of other anticoagulants for this disorder.
Neonatal purpura fulminans is fatal without replacement of protein C (using normal plasma or purified concentrate), along with anticoagulation with heparin or low molecular weight heparin.