Protein C is a key enzyme in the regulation of coagulation and inflammatory response. Activated protein C inactivates factor Va and VIIIa, thereby inhibiting thrombin formation and coagulation. In addition, protein C exhibits direct and indirect anti-inflammatory activities. Protein C deficiency is inherited in an autosomal dominant manner and characterized by variable penetrance.
Protein C is encoded by the PROC gene consisting of 9 exons. Heterozygous carriers of PROC variants with plasma protein C concentrations that are 25-70% of the standard level occur in the general population at a frequency of 1:200-500, but they are symptomatic in only 1:16,000 cases. Homozygous or combined heterozygous patients with plasma protein C concentrations below 25% sometimes develop purpura fulminans, skin necrosis, and intravascular disseminating coagulation at birth, while others experience thrombosis first in adulthood. Heterozygous carriers have an increased risk of venous thrombosis from childhood.
Two types of protein C deficiency can be distinguished:
- Type I: with a simultaneous reduction in concentration and function
- Type II: with a normal or increased concentration and reduced function
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