Because activated protein C degrades clotting factors Va and VIIIa, deficiency of protein C predisposes to venous thrombosis.

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 from genetic or acquired causes promotes venous thrombosis. 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, severe neonatal disseminated intravascular coagulation (DIC). Acquired decreases occur in patients with liver disease or DIC, during cancer chemotherapy (including l-asparaginase administration), and during warfarin therapy.

Diagnosis is based on antigenic and functional plasma assays.

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 most vitamin K–dependent clotting factors. Neonatal purpura fulminans is fatal without replacement of protein C (using normal plasma or purified concentrate) and anticoagulation with heparin or low molecular weight heparin.

Last full review/revision January 2013 by Joel L. Moake, MD