Protein and Coagulation

What is the role of Protein C in blood coagulation?

Effective blood coagulation depends on the correct balance and interaction of different pro- and anti-coagulation factors, as well as vessel wall elements and cellular components of the blood.¹

Protein C (PC), a naturally occurring vitamin K-dependent anti-coagulant, is an important component of the coagulation cascade.^1,2 Its primary role is to regulate the activity of the coagulant thrombin, which, once activated, leads to fibrin formation and blood clotting.^1.2

Overview of the activation and role of protein C

PC is synthesized in the liver as an inactive enzyme precursor known as a zymogen.¹
PC is converted to its active form by forming a complex with the thrombin-thrombomodulin complex on the surface of endothelial cells, facilitated by binding to the endothelial PC receptor (EPCR).¹
Activated PC (APC) inactivates the procoagulation factors V_a (FV_a) and VIII_a (FVIII_a) that promote the generation of thrombin from its precursor molecule prothrombin.¹
PC activation ultimately leads to thrombin inactivation, thereby inhibiting blood clotting. This inactivation occurs at the location of thrombin formation.^1,4
PC also has an indirect pro-fibrinolytic (i.e., clot breakdown) function as it binds to plasminogen activation inhibitor-1 (PAI-1), thereby increasing the activity of tissue type plasminogen activator (tPA).³
Due to reduced thrombin generation, the activation of thrombin activatable fibrinolysis inhibitor (TAFI; an inhibitor of plasmin) is diminished as a result of PC activity, thus resulting in increased clot breakdown.^1,3
PC also has anti-inflammatory and cytoprotective functions.^1,3
The half-life of APC in plasma is about 20 minutes. Once formed, it is immediately degraded by the protein C inhibitor (PCI) and α¹-antitrypsin and, to a lesser extent, α²-macroglobulin and α²-antiplasmin.¹

References:

Mosnier LO, et al. Protein C, Protein S, Thrombomodulin, and the Endothelial Protein C Receptor Pathways. In: Marder, VJ, et al. (eds.) Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 6th ed. Philadelphia, PA, USA: Wolters Kluwer Health; 2012.
Goldenberg N, Manco-Johnson M. Protein C deficiency. Haemophilia. 2008;14(6):1214–1221.
Knoebl PN. Human protein C concentrates for replacement therapy in congenital and acquired protein C deficiency. Drugs of Today. 2008;44(6):429-441.
Gale KD. Continuing Education Course #2: Current Understanding of Hemostasis. Toxicol Pathol. 2011;39(1):273-280.

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Protein and Coagulation

Overview of the activation and role of protein C

Interested in Severe Congenital Protein CDeficiency (SCPCD) and its management?Sign up below!

Interested in Severe Congenital Protein C
Deficiency (SCPCD) and its management?
Sign up below!