Protein C is a normally occurring vitamin K-dependent anticoagulation protein produced by the liver. Protein C deficiency causes increased risk of venous thromboembolism (VTE), mostly in deep veins of the legs (ie, deep vein thrombosis), mesenteric veins, and pulmonary vessels (in the form of pulmonary embolism). Other sites may be affected as well (cerebral vein, portal vein, etc). The incidence of protein C deficiency is approximately 0.2%-0.5% in the general population and approximately 2%-5% in patients with VTE.

Two subtypes are described. Type 1 deficiency refers to reduced protein C antigen and activity levels due to mutation in the PROC gene. Type 2 deficiency refers to a qualitative defect (reduced protein C function with normal antigen levels) also caused by mutation in the PROC gene.

Most cases are heterozygous, although rare cases of homozygous or compound heterozygous mutation have been described. If a mutant allele is inherited from both parents, the results can be severe deficiency of protein C, causing neonatal purpura fulminans at birth.

Acquired cases of protein C deficiency can develop in a variety of scenarios, including hepatic congestion in the setting of right heart failure, severe liver disease, vitamin K deficiency, sepsis, bacterial infection, uremia, acute thrombosis, warfarin or vitamin K antagonist use, certain chemotherapy agents, and disseminated intravascular coagulation.

Patients with protein C deficiency are at an increased risk of developing VTE due to immobility, surgery, trauma, pregnancy, oral contraceptive use, or cancer.