Современные направления в исследованиях свертывания крови

Свертывание крови происходит в условиях ее тока и стазиса, оно задействует компоненты клеточного гемостаза и ферментативные каскады реакций, служит для остановки кровотечений и может приводить к возникновению угрожающих жизни тромбов. Несмотря на то, что полный список белков свертывания сформировался несколько десятилетий назад, за последние годы накопилась многочисленная новая информация о его устройстве и регуляции, что привело к созданию новых методов диагностики его нарушений и способов их коррекции. Врожденные и приобретенные нарушения свертывания крови до сих пор остаются острой клинической проблемой. В данном обзоре показаны современные представления об устройстве и функционировании системы свертывания крови в различных условиях.

свертывание крови, регуляция свертывания, фибринолиз

1. Marder V.J., Aird W.C., Bennett J.S., Schulman S., White G.C. II. Hemostasis and Thrombosis: Basic principles and clinical practice. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2013.

2. Panteleev M.A., Dashkevich N.M., Ataullakhanov F.I. Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion. Thromb Res 2015; 136 (4): 699–711. DOI: 10.1016/j.thromres.2015.07.025

3. Conway E.M. Complement-coagulation connections. Blood Coagul Fibrinolysis 2018; 29 (3): 243–51. DOI: 10.1097/MBC.0000000000000720

4. Gaertner F., Massberg S. Blood coagulation in immunothrombosis-At the frontline of intravascular immunity. Semin Immunol 2016; 28 (6): 561–9. DOI: 10.1016/j.smim.2016.10.010

5. Periayah M.H., Halim A.S., Mat Saad A.Z. Mechanism Action of Platelets and Crucial Blood Coagulation Pathways in Hemostasis. Int J Hematol Stem Cell Res 2017; 11 (4): 319–27.

6. Key N.S., Makris M., Lillicrap D. (eds.). Practical Hemostasis and Thrombosis. Third ed. Chichester, West Sussex: John Wiley & Sons; 2017.

7. Davie E.W., Fujikawa K., Kurachi K. The role of serine proteases in the blood coagulation cascade. Adv Enzym Relat Areas Mol Biol 1979; 48: 277–318. DOI: 10.1002/9780470122938.ch6

8. Davie E.W., Fujikawa K., Kisiel W. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 1991; 30 (43): 10363–70. DOI: 10.1021/bi00107a001

9. Zwaal R.F.A. Membrane and lipid involvement in blood coagulation. Biochim Biophys Acta 1978; 515 (2): 163–205. DOI: 10.1016/0304-4157(78)90003-5

10. Takahashi M., Yamashita A., Moriguchi-Goto S., Sugita C., Matsumoto T., Matsuda S., еt al. Inhibition of factor XI reduces thrombus formation in rabbit jugular vein under endothelial denudation and/or blood stasis. Thromb Res 2010; 125 (5): 464–70. DOI: 10.1016/j.thromres.2009.12.013

11. Morrison D.C., Cochrane C.G. Direct evidence for Hageman factor (factor XII) activation by bacterial lipopolysaccharides (endotoxins). J Exp Med 1974; 140 (3): 797–811. DOI: 10.1084/jem.140.3.797

12. Brinkmann V., Reichard U., Goosmann C., Fauler B., Uhlemann Y., Weiss D.S., еt al. Neutrophil extracellular traps kill bacteria. Science 2004; 303 (5663): 1532–5. DOI: 10.1126/science.1092385

13. Urban C.F., Reichard U., Brinkmann V., Zychlinsky A. Neutrophil extracellular traps capture and kill Candida albicans yeast and hyphal forms. Cell Microbiol 2006; 8 (4): 668–76. DOI: 10.1111/j.1462-5822.2005.00659.x

14. Saitoh T., Komano J., Saitoh Y., Misawa T., Takahama M., Kozaki T., еt al. Neutrophil extracellular traps mediate a host defense response to human immunodeficiency virus-1. Cell Host Microbe 2012; 12 (1): 109–16. DOI: 10.1016/j.chom.2012.05.015

15. Fuchs T.A., Brill A., Duerschmied D., Schatzberg D., Monestier M., Myers D.D., еt al. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA 2010; 107 (36): 15880–5. DOI: 10.1073/pnas.1005743107

16. Massberg S., Grahl L., von Bruehl M.L., Manukyan D., Pfeiler S., Goosmann C., еt al. Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med 2010; 16 (8): 887–96. DOI: 10.1038/nm.2184

17. Ammollo C.T., Semeraro F., Xu J., Esmon N.L., Esmon C.T. Extracellular histones increase plasma thrombin generation by impairing thrombomodulin-dependent protein C activation. J Thromb Haemost 2011; 9 (9): 1795–803. DOI: 10.1111/j.1538-7836.2011.04422.x

18. von Brühl M.L., Stark K., Steinhart A., Chandraratne S., Konrad I., Lorenz M., et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 2012; 209 (4): 819–35. DOI: 10.1084/jem.20112322

19. Brill A., Fuchs T.A., Savchenko A.S., Thomas G.M., Martinod K., De Meyer S.F., et al. Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost 2012; 10 (1): 136–44. DOI: 10.1111/j.1538-7836.2011.04544.x

20. Levin E.G., Marzec U., Anderson J., Harker L.A. Thrombin stimulates tissue plasminogen activator release from cultured human endothelial cells. J Clin Invest 1984; 74 (6): 1988–95. DOI: 10.1172/JCI111620

21. Booth N.A., Simpson A.J., Croll A., Bennett B., MacGregor I.R. Plasminogen activator inhibitor (PAI-1) in plasma and platelets. Br J Haematol 1988; 70 (3): 327–33. DOI: 10.1111/j.1365-2141.1988.tb02490.x

22. Brogren H., Wallmark K., Deinum J., Karlsson L., Jern S. Platelets Retain High Levels of Active Plasminogen Activator Inhibitor 1. PLoS One 2011; 6 (11): e26762. DOI: 10.1371/journal.pone.0026762

23. Carr M.E. Development of platelet contractile force as a research and clinical measure of platelet function. Cell Biochem Biophys 2003; 38 (1): 55–78. DOI: 10.1385/CBB:38:1:55

24. Fox J.E. The platelet cytoskeleton. Thromb Haemost 1993; 70 (6): 884–93.

25. Phillips D.R., Charo I.F, Scarborough R.M. GPIIb–IIIa: the responsive integrin. Cell 1991; 65 (3): 359–62. DOI: 10.1016/0092-8674(91)90451-4

26. Murrell M., Oakes P.W., Lenz M., Gardel M.L. Forcing cells into shape: the mechanics of actomyosin contractility. Nat Rev Mol Cell Biol 2015; 16 (8): 486– 98. DOI: 10.1038/nrm4012

27. Schoenwaelder S.M., Ono A., Nesbitt W.S., Lim J., Jarman K., Jackson S.P. Phosphoinositide 3-Kinase p110b Regulates Integrin a IIb b 3 Avidity and the Cellular Transmission of Contractile Forces. J Biol Chem 2010; 285 (4): 2886–96. DOI: 10.1074/jbc.M109.029132

28. Wufsus A.R., Rana K., Brown A., Dorgan J.R., Liberatore M.W., Neeves K.B. Elastic behavior and platelet retraction in low- and high-density fibrin gels. Biophys J 2015; 108 (1): 173–83. DOI: 10.1016/j. bpj.2014.11.007

29. Stalker T.J., Welsh J.D., Tomaiuolo M., Wu J., Colace T.V., Diamond S.L., Brass L.F. A systems approach to hemostasis: 3. Thrombus consolidation regulates intrathrombus solute transport and local thrombin activity. Blood 2014; 124 (11): 1824– 31. DOI: 10.1182/blood-2014-01-550319

30. Weisel J.W. Biophysics. Enigmas of blood clot elasticity. Science 2008; 320 (5875): 456–7. DOI: 10.1126/science.1154210

31. Kunitada S., FitzGerald G.A., Fitzgerald D.J. Inhibition of clot lysis and decreased binding of tissue-type plasminogen activator as a consequence of clot retraction. Blood 1992; 79 (6): 1420–7.

32. Tutwiler V., Peshkova A.D., Le Minh G., Zaitsev S., Litvinov R.I., Cines D.B., Weisel J.W. Blood clot contraction differentially modulates internal and external fibrinolysis. J Thromb Haemost 2019; 17 (2): 361–70. DOI: 10.1111/jth.14370

33. Huber-Lang M., Sarma J.V., Zetoune F.S., Rittirsch D., Neff T.A., McGuire S.R., et al. Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med 2006; 12 (6): 682–7. DOI: 10.1038/nm1419

34. Davis A.E. Biological effects of C1 inhibitor. Drug News Perspect 2004; 17 (7): 439–46. DOI: 10.1358/dnp.2004.17.7.863703

35. Ikeda K., Nagasawa K., Horiuchi T., Tsuru T., Nishizaka H., Niho Y. C5a induces tissue factor activity on endothelial cells. Thromb Haemost 1997; 77 (2): 394–8.

36. Bosmann M., Grailer J.J., Ruemmler R., Russkamp N.F., Zetoune F.S., Sarma J.V., еt al. Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury. FASEB J 2013; 27 (12): 5010– 21. DOI: 10.1096/fj.13-236380

37. Wojta J., Huber K., Valent P. New aspects in thrombotic research: complement induced switch in mast cells from a profibrinolytic to a prothrombotic phenotype. Pathophysiol Haemost Thromb 2004; 33 (5–6): 438–41. DOI: 10.1159/000083842

38. Martel C., Cointe S., Maurice P., Matar S., Ghitescu M., Théroux P., Bonnefoy A. Requirements for membrane attack complex formation and anaphylatoxins binding to collagen-activated platelets. PLoS One 2011; 6 (4): e18812. DOI: 10.1371/journal.pone.0018812

39. Del Conde I., Crúz M.A., Zhang H., López J.A., Afshar-Kharghan V. Platelet activation leads to activation and propagation of the complement system. J Exp Med 2005; 201 (6): 871–9. DOI: 10.1084/jem.20041497

40. Antoniak S., Mackman N. Multiple roles of the coagulation protease cascade during virus infection. Blood 2014; 123 (17): 2605–13. DOI: 10.1182/blood-2013-09-526277

41. Nhu Q.M., Shirey K., Teijaro J.R., Farber D.L., Netzel-Arnett S., Antalis T.M., еt al. Novel signaling interactions between proteinase-activated receptor 2 and Tolllike receptors in vitro and in vivo. Mucosal Immunol 2010; 3 (1): 29–39. DOI: 10.1038/mi.2009.120

42. Antoniak S., Tatsumi K., Bode M., Vanja S., Williams J.C., Mackman N. Protease-Activated Receptor 1 Enhances Poly I:C Induction of the Antiviral Response in Macrophages and Mice. J Innate Immun 2017; 9 (2): 181–92. DOI: 10.1159/000450853

43. Verschoor A., Neuenhahn M., Navarini A.A., Graef P., Plaumann A., Seidlmeier A., et al. A platelet-mediated system for shuttling blood-borne bacteria to CD8a+ dendritic cells depends on glycoprotein GPIb and complement C3. Nat Immunol 2011; 12 (12): 1194–201. DOI: 10.1038/ni.2140

44. Guidotti L.G., Inverso D., Sironi L., Di Lucia P., Fioravanti J., Ganzer L., et аl. Immunosurveillance of the liver by intravascular effector CD8(+) T cells. Cell 2015; 161 (3): 486–500. DOI: 10.1016/j.cell.2015.03.005

45. Maugeri N., Brambilla M., Camera M., Carbone A., Tremoli E., Donati M.B., et al. Human polymorphonuclear leukocytes produce and express functional tissue factor upon stimulation. J Thromb Haemost 2006; 4 (6): 1323–30. DOI: 10.1111/j.1538-7836.2006.01968.x

46. Parry G.C., Mackman N. Transcriptional regulation of tissue factor expression in human endothelial cells. Arterioscler Thromb Vasc Biol 1995; 15 (5): 612–21. DOI: 10.1161/01.atv.15.5.612

47. Houston P., Dickson M.C., Ludbrook V., White B., Schwachtgen J.L., McVey J.H., et al. Fluid shear stress induction of the tissue factor promoter in vitro and in vivo is mediated by Egr-1. Arterioscler Thromb Vasc Biol 1999; 19 (2): 281–9. DOI: 10.1161/01.atv.19.2.281

48. Slupsky J.R., Kalbas M., Willuweit A., Henn V., Kroczek R.A., Müller-Berghaus G. Activated platelets induce tissue factor expression on human umbilical vein endothelial cells by ligation of CD40. Thromb Haemost 1998; 80 (6): 1008–14.

49. Semeraro N., Triggiani R., Montemurro P., Cavallo L.G., Colucci M. Enhanced endothelial tissue factor but normal thrombomodulin in endotoxin-treated rabbits. Thromb Res 1993; 71 (6): 479–86. DOI: 10.1016/0049-3848(93)90121-4

50. Erlich J., Fearns C., Mathison J., Ulevitch R.J., Mackman N. Lipopolysaccharide induction of tissue factor expression in rabbits. Infect Immun 1999; 67 (5): 2540–6.

51. Dittman W.A., Majerus P.W. Structure and function of thrombomodulin: a natural anticoagulant. Blood 1990; 75 (2): 329–36.

52. Girard T.J., Tuley E., Broze G.J. TFPIb is the GPI-anchored TFPI isoform on human endothelial cells and placental microsomes. Blood 2012; 119 (5): 1256–62. DOI: 10.1182/blood-2011-10-388512

53. Turner N., Nolasco L., Tao Z., Dong J.F., Moake J. Human endothelial cells synthesize and release ADAMTS-13. J Thromb Haemost 2006; 4 (6): 1396–404.

54. Everett L.A., Cleuren A.C.A., Khoriaty R.N., Ginsburg D. Murine coagulation factor VIII is synthesized in endothelial cells. Blood 2014; 123 (24): 3697–705. DOI: 10.1182/ blood-2014-02-554501

55. Pan J., Dinh T.T., Rajaraman A., Lee M., Scholz A., Czupalla C.J., et аl. Patterns of expression of factor VIII and von Willebrand factor by endothelial cell subsets in vivo. Blood 2016; 128 (1): 104–9. DOI: 10.1182/blood-2015-12-684688

56. Jha N.K., Shestopal S.A., Gourley M.J., Woodle S.A., Liang Y., Sarafanov A.G.,et al. Optimization of the thrombin generation test components to measure potency of factor VIII concentrates. Haemophilia 2016; 22 (5): 780–9. DOI: 10.1111/ hae.12943

57. Ovanesov M.V., Krasotkina J.V., Ul’yanova L.I., Abushinova K.V., Plyushch O.P., Domogatskii S.P., et al. Hemophilia A and B are associated with abnormal spatial dynamics of clot growth. Biochim Biophys Acta 2002; 1572 (1): 45–57. DOI: 10.1016/s0304-4165(02)00278-7

58. Shibeko A.M., Lobanova E.S., Panteleev M.A., Ataullakhanov F.I. Blood flow controls coagulation onset via the positive feedback of factor VII activation by factor Xa. BMC Syst Biol 2010; 4: 5. DOI: 10.1186/1752-0509-4-5

59. Ataullakhanov F.I., Guriia G.T. Spatial aspects of the dynamics of blood coagulation. I. Hypothesis. Biofizika 1994; 39 (1): 89–96.

60. Zhalyalov A.S., Panteleev M.A., Gracheva M.A., Ataullakhanov F.I., Shibeko A.M. Co-ordinated spatial propagation of blood plasma clotting and fibrinolytic fronts. PLoS One 2017; 12 (7): e0180668. DOI: 10.1371/journal.pone.0180668