protein c

Protein C is a major physiological anticoagulant. It is a vitamin K-dependant serine protease enzyme (EC 3.4.21.69) that is activated by thrombin into activated protein C (APC). The activated form (with protein S as a cofactor) degrades Factor Va and Factor VIIIa.

Genetics

The PROC gene is located on the second chromosome (2q13-q14).

Role in disease

Protein C deficiency is a rare genetic disorder that predisposes to venous thrombosis and habitual abortion. If homozygous, this presents with a form of disseminated intravascular coagulation in newborns termed purpura fulminans; it is treated by replacing the defective protein C. Activated protein C resistance is the inability of protein C to cleave factors V and/or VIII. This may be hereditary or acquired. The best known and most common hereditary form is Factor V Leiden. Acquired forms occur in the presence of elevated Factor VIII concentrations. Warfarin necrosis is acquired protein C deficiency due to treatment with the vitamin K inhibitor anticoagulant warfarin. In initial stages of action, inhibition of protein C may be stronger than inhibition of the vitamin K-dependant coagulation factors (II, VII, IX and X), leading to paradoxical activation of coagulation and necrosis of skin areas.

Pharmacology

Drotrecogin alpha (activated) is recombinant activated protein C. It is used in the treatment of sepsis and disseminated intravascular coagulation.

External link

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