Protein C
Biochemistry
| Molecular weight | 62.000 Da |
|---|---|
| Synthesis | Liver |
| Half-life | 6 - 8 hours |
| Plasma-concentration | 3 - 5 µg/ml, 63 nmol/l |
| Primary structure | 1 light (155 amino acids) and 1 heavy (262 amino acids) polypeptide chain connected by one disulfide bridge |
| Normal range | 70 - 120% |
Activated Protein C is a vitamin K-dependent protein and one of the most important coagulation inhibitors. Its inactive precursor, Protein C, is activated by cleavage of a small N-terminal activation peptide (14 amino acids) from the heavy chain. This occurs in vivo by the surface-bound thrombin/thrombomodulin complex on the endothelium. Some snake venoms are also known to activate Protein C. Activated protein C (APC) is a serine protease that in complex with protein S by proteolytic cleavage of the activated coagulation factors Va and VIIIa inactivate the coagulation. This causes down-regulation of the thrombin generation. The activity of APC in plasma is regulated by at least three inhibitors: Protein C inhibitor (PAI-3), α1-antitrypsin and α2-macroglobulin. The inhibition by the Protein C-Inhibitor is heparin dependent.
Clinical Significance
With the autosomally dominant hereditary form of the Protein C deficiency discrimination is made between type I (activity and antigen reduced), and type II (activity reduced). The most frequent clinical manifestation in patients with heterozygous Protein C deficiency is deep vein thrombosis. Thromboembolic diseases usually present at young age, especially in the presence of further risk factors such as pregnancy, surgery, immobilisation or the use of oral contraceptives. A homozygous Protein C deficiency is expressed by the occurrence of a usually fatal thrombosis in new-borns, known as purpura fulminans. An acquired Protein C deficiency can be due to various diseases and medications, e.g. DIC, deep vein thrombosis, liver disease, sepsis, vitamin K-deficiency or a therapy with oral anticoagulants. During the initial phase of an oral anticoagulant therapy a remarkable reduction in the Protein C activity may be observed, which can result in the formation of so-called coumarin necrosis. This applies especially in the presence of a hereditary Protein C deficiency.
Indication
- Suspected hereditary Protein C deficiency (recurring thrombosis, thromboembolic complications at young age, Purpura fulminans, Coumarin necrosis)
- Suspected acquired Protein C deficiency (DIC, liver disease, oral anticoagulants)
- Diagnosis of thrombophilia
Literature
- Faioni EM et al. Resistance to activated protein C mimicking dysfunctional protein C: diagnostic approach. Blood Coag Fibrinol 7, 349-352, 1996.
- Fujita M et al. Effect of Urinary Protein C Inhibitor on LPS-induced Disseminated Intravascular Coagulation in Rats. Thromb Haemost 84, 54-58, 2000.
- Wendel HP et al. Aprotinin in therapeutic doses inhibits chromogenic peptide substrate assays for Protein C. Thromb Res 74, 543-548, 1994.
- Dahlbäck B. The Protein C anticoagulant system: Inherited defects as basis for venous thrombosis. Thromb Res 77, 1-43, 1995.
- Watanabe R et al. Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable states. Am J Hematol 65, 35-40, 2000.
- Bock F, Shahzad K, Vergnolle N, Isermann B. Activated protein C based therapeutic strategies in chronic diseases. Thromb Haemost. Apr 1, 111(4), 610-7, 2014.
- Manco-Johnson MJ, Bomgaars L, Palascak J, Shapiro A, Geil J, Fritsch S, Pavlova BG, Gelmont D. Efficacy and safety of pro-tein C concentrate to treat purpura fulminans and thromboembolic events in severe congenital protein C deficiency. Thromb Haemost. Jul 4, 116(1), 58-6, 2016.