**8.2 Protein C and protein S deficiency**

Protein C is a vitamin K dependent anticoagulant protein that, once activated by thrombin, will inactivate factors Va and VIIIa, thereby inhibiting the generation of thrombin.83 Additionally, activated protein C stimulates the release of t-PA. It is produced in the liver and is the dominant endogenous anticoagulant with an eight-hour half-life. Protein C deficiency has a prevalence of 1 in 200–300 with more than 150 mutations and an autosomal dominant inheritance.83,84

Protein S is also a vitamin K dependent anticoagulant protein that is a cofactor to activated protein C. The actions of protein S are regulated by complement C4b binding protein and only the free form of protein S serves as an activated protein C cofactor.85 Additionally, protein S appears to have independent anticoagulant function by directly inhibiting procoagulant enzyme complexes.84,86 The prevalence of protein S defi ciency is about 1 : 500 with an autosomal dominant inheritance.

Clinically, protein C and S deficiencies are essentially identical. With homozygous protein C and S defi ciencies, infants typically will succumb to purpura fulminans, a state of unrestricted clotting and fi brinolysis. In heterozygotes, venous thromboses may occur at an early age especially in the lower extremity.87 Thrombosis may also occur in mesenteric, renal, and cerebral veins.
