Activated protein C

Inhibits platelet aggregation by increasing levels of cAMP Binds protein C, which is then cleaved by thrombin to yield activated protein C this in combination with protein S degrades factors Va and Villa, limiting their actions Activates plasminogen to plas-min, which digests fibrin the action of t-PA is opposed by plasminogen activator inhibitor- (PAI-1)... 

Protein C, protein S, antithrombin III, activated protein C resistance, lipoprotein(a) anticardiolipin antibodies, lupus anticoagulant, prothrombin gene mutation 20210a... 

The inflammatory process in sepsis is linked to the coagulation system. Pro-inflammatory mediators maybe procoagulant and antifibrinolytic, whereas anti-inflammatory mediators may be fibrinolytic. A key factor in the inflammation of sepsis is activated protein C, which enhances fibrinolysis and inhibits inflammation. Protein C levels are decreased in septic patients. 

Activated protein C in patients with severe sepsis and high risk of death (Acute Physiology, Age, and Chronic Health Evaluation II [APACHE II] score greater than 25). 

Bernard GR, Vincent JL, Laterre PF, et al. Recombinant Human Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001 344 699-709. 

F16. De Fouw, N. J., Van Hinsbergh, V. W. M., De Jong, Y. F Haverkate, F., and Bertina, R. M., The interaction of activated protein C and thrombin with the plasminogen activator inhibitor released from human endothelial cells. Thromb. Haemost. 57, 176-182 (1987). 

A type I transmembrane protein called endothelial cell protein C receptor (EPCR), which is expressed at high levels exclusively on a subset of endothelial cells, has also been identified. EPCR has a role in the protein C pathway (30). EPCR binds to both protein C and activated protein C (APC) with equal affinity. Activation of protein C presumably requires interaction of the protein C-EPCR complex with the thrombin-thrombomodulin complex. APC that is formed as a result of this interaction is reversibly bound to EPCR until it dissociates to react subsequently with protein S. The APC-protein S complex inactivates activated factor V (Va). 

Although the fibrinolytic pathway is activated when thrombin binds to thrombomodulin, the thrombin-thrombomodulin complex, in addition to activating protein C (APC), activates a fibrinolysis inhibitor called the thrombin-activatable fibrinolysis inhibitor (TAFIa). Thus plasmin generation and, in turn, fibrinolysis are... 

Other plasminogen activator inhibitors are PAI-3, which is believed to be identical to the activated protein C inhibitor, and proteinase nexin 1, found in the renal epithelial cells, cytosol of fibroblasts, and cardiac myocytes (37, 42, 44, 45). 

Dahlback B. Resistance to activated protein C, the Arg506 to Gin mutation in the factor V gene and venous thrombosis. Functional tests and DNA based assays, pros and cons. Thromb Haemost, 1995 73,739-42. 

Thrombomodulin is a protein on the endothelium that (1) binds with thrombin, reducing its availability for the clotting process and (2) activates protein C, which acts as an anticoagulant by inactivating factors V and VIII. 

Yegneswaran, S., Kojima, Y., Nguyen, P.M., Gale, A.J., Heeb, M.J., and Griffin, J.H. (2007) Factor Va residues 311-325 represent an activated protein C binding region./. Biol. Chem. 10.1074/jbc.M704316200. 

Hypercoagulable states include malignancy activated protein C resistance deficiency of protein C, protein S, or antithrombin factor VIII or XI excess antiphospholipid antibodies and other situations. Estrogens and selective estrogen receptor modulators have been linked to venous thrombosis, perhaps due in part to increased serum clotting factor concentrations. Although a thrombus can form in any part of the venous circulation, the majority of thrombi begin in the lower extremities. Once formed, a venous... 

Proinflammatory mechanisms in sepsis are also procoagulant and antifibrinolytic. Levels of activated protein C, a fibrinolytic and antiinflammatory substance, are decreased in sepsis. 

Protein S The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors Villa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH]... 

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