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This article is focused on the pathophysiology, prevalence , clinical manifestations, diagnosis, and treatment C deficiency with increased risk of thrombosis. Activated protein C (aPC) exerts its anticoagulant activity through inactivation of coagulation factors Va and VIIIa. Aside its anticoagulant property, aPC demonstrates anti-inflammatory and cytoprotectiveeffects, which are mediated through the endothelial protein C receptor and the protease-activated receptor-I (PAR-1). Studying and understanding the biological function of APS makes it possible to control coagulation and inflammation and to apply protein C preparations as anticoagulant and cytoprotective drugs in a physicians clinical

About the Author

I. A. Mikhaylidi
The State Education Institution of Higher Professional Training The First Sechenov Moscow State Medical University under Ministry of Health of the Russian Federation
Russian Federation


1. Alonso A., Soto I., Urgelles M.F. et al. Acquired and inherited thrombophilia in women with unexplained fetal losses. Am. J. Obstet. Gynecol. 2002; 187: 1337-1342.

2. Ananth C.V., Nath C.A., Philipp C. The Normal anticoagulant system and risk of placental abruption: protein C, protein S and resistance to activated protein C. J. Matern. Fetal. Neonatal. Med. 2010. 23 (12): 1377-83.

3. Andersson H.M., Arantes M.J., Crawley J.T. et al. Activated protein C cofactor function of protein S: a critical role for Asp95 in the EGF1– like domain. Blood. 2010; 115 (23): 4878-85.

4. Barie P.S., Hydo L.J., Shou J. et al. Efficacy of therapy with recombinant human activated protein C of critically ill surgical patients with infection complicated by septic shock and multiple organ dysfunction syndrome. Surg. Infect. (Larchmt). 2011; 12 (6): 443-9.

5. Bergrem A., Dahm A.E., Jacobsen A.F., Mowinckel M.C. Resistance to activated protein C is a risk factor for pregnancy–related venous thrombosis in the absence of the F5 rs6025 (factor V Leiden) polymorphism. Br. J. Haematol. 2011; 154 (2): 241-7.

6. Dawood F., Farquharson R., Quenby S., Toh C.H. Acquired activated protein C resistance may be a risk factor for recurrent fetal loss. Fertil. Steril. 2003; 80 (3): 649-50.

7. Esmon C.T. Inflammation and the activated protein C anticoagulant pathway. Semin. Thromb. Hemost. 2006; 1: 49-60.

8. Gorbacheva L., Pinelis V., Ishiwata S., Strukova S. et al. Activated protein C prevents glutamate – and thrombin-induced activation of nuclear factor – kappaB in cultured hippocampal neurons. Neuroscience. 2010; 165 (4): 1138-46.

9. Gorbacheva L.R., Storozhevykh T.P., Pinelis V.G. et al. Activated protein C via PAR1 receptor regulates survival of neurons under conditions of glutamate excitotoxicity. Biochemistry (Mosc). 2008; 73 (6): 717-24. 10. Griffin J.H., Fernandez J.A., Gale A.J. et al. Activated protein C. J. Thromb. Haemost. 2007; 1: 73-80.

10. Hackeng T.M., Rosing J. Protein S as cofactor for TFPI. Arterioscler. Thromb. Vasc. Biol. 2009; 29 (12): 2015-20.

11. Hussein A.S., Darwish H., Shelbayeh K. Association between factor V Leiden mutation and poor pregnancy outcomes among Palestinian women. Thromb. Res. 2010; 126 (2): 78-82.

12. Ivanov P., Komsa–Penkova R., Konova E., Gecheva S. Combined thrombophilic factors among women with late recurrent spontaneous abortions. Akush. Ginekol. (Sofiia). 2011; 50 (3): 8-12.

13. Underwood J., Regan L. Genetic thrombophilic mutations among couples with recurrent miscarriage. Human Reproduction. 2006; 21 (5): 1161-1165.

14. Mille-Baker B., Rezende S.M., Simmonds R.E. et al. Deletion or replacement of the second EGF – like domain of protein S results in loss of APC cofactor activity Blood. 2003; 101 (4): 1416-8.

15. Mohamed M.A., El Moaty M.A., El Kholy A.F., Mohamed S.A. et al. Thrombophilic gene mutations in women with repeated spontaneous miscarriage. Genet. Test. Mol. Biomarkers. 2010; 14 (5): 593-7.

16. Mosnier L.O., Zlokovic B.V., Griffin J.H. The cytoprotective protein C pathway. Blood. 2007;109: 3161-3172.

17. Murakami M.T., Arni R.K. Thrombomodulin–independent activation of protein C and specificity of hemostatically active snake venom serine proteinases: crystal structures of native and inhibited Agkistrodon contortrix contortrix protein C activator. J. Biol. Chem. 2005; 280 (47): 39309-15.

18. Nojima J., Iwatani Y., Ichihara K., Tsuneoka H. et all Acquired activated protein C resistance is associated with IgG antibodies to protein S in patients with systemic lupus erythematosus. Thromb. Res. 2009; 124 (1): 127-31.

19. Nojima J., Kuratsune H., Suehisa E., Iwatani Y. et all. Acquired activated protein C resistance associated with IgG antibodies against beta2–glycoprotein I and prothrombin as a strong risk factor for venous thromboembolism. Clin. Chem. 2005; 51 (3): 545-52.

20. Norström E., Thorelli E., Dahlbäck B. Functional haracterization of recombinant FV Hong Kong and FV Cambridge. Blood. 2002; 100 (2): 524-30.

21. Olivieri O., Friso S., Manzato F. et all. Resistance to activated protein C in healthy women taking oral contraceptives. Br. J. Haematol. 1995; 91: 465-470.

22. Procházka M., Lubuský M., Slavík L., Hrachovec P., Zielina P. et all Frequency of selected thrombophilias in women with placental abruption. Aust. N. Z. J. Obstet. Gynaecol. 2007; 47 (4): 297-301.

23. Rai R., Shlebak A., Cohen H., Backos M. et all. Factor V Leiden and acquired activated protein C resistance among 1000 women with recurrent miscarriage. Human Reproduction. 2001; 16 (5): 961-965.

24. Rey E., Kahn S.R., David M., Shrier I. Thrombophilic disorders and fetal loss: a metaanalysis. Lancet. 2003; 361: 901-908.

25. Rezaie A.R. Regulation of the protein C anticoagulant and nti-inflammatory pathways. Curr. Med. Chem. 2010; 17: 2059-2069.

26. Rosendorff A., Dorfman D.M. Activated protein c resistance and factor V Leiden: a review. Arch. Pathol. Lab. Med. 2007; 131: 866-71.

27. Saposnik B., Borgel D., Aiach M. et al. Functional properties of the sex–hormone–binding globulin (SHBG)–like domain of the anticoagulant protein S. Eur. J. Biochem. 2003; 270 (3): 545-55.

28. Sarangi P.P., Lee H.W., Kim M. Activated protein C action in inflammation. Br. J. Haematol. 2010; 148 (6): 817-33.

29. Sedano-Balb´ as S., Lyons M., Cleary B., Murray all. Acquired activated protein c resistance, thrombophilia and adverse pregnancy outcomes: a study performed in an irish cohort of pregnantwomen. J. Pregnancy. 2011; 1-9.

30. Sedano–Balbás S., Lyons M., Cleary B., Murray M. et all. APCR, factor V gene known and novel SNPs and adverse pregnancy outcomes in an Irish cohort of pregnant women. Pregnancy Childbirth. 2010; 10 (11): 1-8.

31. Sotiriadis A., Vartholomatos G., Pavlou M. et al. Combined thrombophilic mutations in women with unexplained recurrent miscarriage. Am. J. Reprod. Immunol. 2007; 57: 133-41.

32. Strukova S.M. Role of platelets and serine proteinases in coupling of blood coagulation and inflammation. Biochemistry. 2004; 69 (10): 1067-81.

33. Tchaikovski S.N., Thomassen M.C., Costa S.D., Peeters L.L., Rosing J. Role of protein S and tissue factor pathway inhibitor in the development of activated protein C resistance early in pregnancy in women with a history of preeclampsia. Thromb. Haemost. 2011; 106 (5): 914-21.

34. Tran S., Dahlback B. Novel APC-cleavage sites in FVa provide insights into mechanisms of action of APC and its cofactor protein S. J. Thromb. Haemost. 2010; 8: 129-136.

35. Weiler H. Multiple receptor–mediated functions of activated protein C. Hämostaseologie. 2011; 31: 185-195.

36. Zangari M., Berno T., Zhan F. et al. Activated protein C resistance as measured by residual factor V after Russell's viper venom and activated protein C treatment analyzed as a continuous variable in multiple myeloma and normal controls. Blood Coagul Fibrinolysis. 2011; 22 (5): 420-3.



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