https://pubmed.ncbi.nlm.nih.gov/2959034/ C T Esmon et al. Adv Exp Med Biol. 1987 Abstract Proteins C and S are two vitamin K-dependent plasma proteins that work in concert as a natural anticoagulant system. Activated protein C is the proteolytic component of the complex and protein S serves as an activated protein C binding protein that is essential for assembly of the anticoagulant complex on cell surfaces. The anticoagulant activity is expressed through the selective inactivation of Factors Va and VIIIa. Many patients deficient in proteins C and S have been described and have an associated thrombotic tendency, but not all heterozygous protein C and S deficient individuals experience thrombotic complications. Multiple mechanisms and/or drugs can lead to acquired deficiencies of these proteins: oral anticoagulation, liver disease, DIC and in the case of protein S, lupus erythematosus, nephrotic syndrome, pregnancy and certain hormones. The anticoagulant activity of protein C decreases rapidly after administration of warfarin (i.e., with a time course similar to Factor VII). This rapid decrease may lead to a transient imbalance and contribute to coumarin induced skin necrosis. Protein S antigen levels do not decrease as rapidly, but protein S functional levels are often low in patients with an acute thrombus. The discrepancy between antigen and function results from elevations in C4b-binding protein, which complexes reversibly with protein S. Unlike free protein S, the complex does not function in the anticoagulant pathway. The available information all suggest that deficiency of protein C and protein S should be considered a risk factor contributing to recurrent thrombotic disease and that the function of these proteins is altered by many common clinical conditions which have associated an increased risk of thrombosis.
