Интегральные лабораторные тесты гемостаза в диагностике гиперкоагуляции и оценке риска тромбоза. Часть II. Чувствительность интегральных тестов к гиперкоагуляционным состояниям

В данной работе представлен обзор существующих данных относительно способности интегральных тестов, как уже введенных в клиническую практику, так и новых (тест генерации тромбина, тромбоэластография, тромбодинамика, перфузионные камеры), оценивать риск тромбоза при различных патологиях. Мы пришли к выводу, что существующие интегральные тесты могут стать важным инструментом в диагностике гиперкоагуляции. Однако имеющийся в настоящее время недостаток стандартизации препятствует их применению: различные тесты и любые их модификации различаются по чувствительности и специфичности для каждого патологического состояния. Кроме того, даже в тех ситуациях, когда тесты могут достоверно выявлять группы пациентов с различной степенью риска тромбоза, их применение в клинической практике для принятия решений часто затруднительно, так как различия между такими группами статистически достоверны, однако диапазоны норм и пациентов значительно перекрываются

интегральные тесты гемостаза, гиперкоагуляция, тромбоз, активированное частичное тромбопластиновое время, тест генерации тромбина, тромбоэластография, тромбодинамика, онкологические заболевания, беременность, сахарный диабет

1. Brummel-Ziedins K.E., Wolberg A.S. Global assays of hemostasis. Curr Opin Hematol 2014;21:395–403.

2. Dargaud Y., Sorensen B., Shima M. et al. Global haemostasis and point of care testing. Haemophilia 2012;18(4):81–8.

3. van Geffen M., van Heerde W.L. Global haemostasis assays, from bench to bedside. Thromb Res 2012;129:681–7.

4. Miller S.P., Sanchez-Avalos J., Stefanski T., Zuckerman L. Coagulation disorders in cancer. I. Clinical and laboratory studies. Cancer 1967;20:1452–65. 5. G ordon E.M., Ratnoff O.D., Jones P.K. The role of augmented Hageman factor (factor XII) titers in the cold-promoted activation of factor VII and spontaneous shortening of the prothrombin time in women using oral contraceptives. J Lab Clin Med 1982;99:363–9.

5. Le vy J.H., Szlam F., Wolberg A.S., Winkler A. Clinical use of the activated partial thromboplastin time and prothrombin time for screening: a review of the literature and current guidelines for testing. Clin Lab Med 2014;34:453–77.

6. Min a A., Favaloro E.J., Mohammed S., Koutts J. A laboratory evaluation into the short activated partial thromboplastin time. Blood Coagul Fibrinolysis 2010;21:152–7.

7. Ten Boekel E., Bartels P. Abnormally short activated partial thromboplastin times are related to elevated plasma levels of TAT, F1+2, D-dimer and FVIII:C. Pathophysiol Haemost Thromb 2002;32:137–42.

8. Tripo di A., Chantarangkul V., Martinelli I. et al. A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism. Blood 2004;104:3631–4.

9. Hron G., Eichinger S., Weltermann A. et al. Prediction of recurrent venous thromboembolism by the activated partial thromboplastin time. J Thromb Haemost 2006;4:752–6.

10. Legnan i C., Mattarozzi S., Cini M. et al. Abnormally short activated partial thromboplastin time values are associated with increased risk of recurrence of venous thromboembolism after oral anticoagulation withdrawal. Br J Haematol 2006;134: 227–32.

11. Hussain N., Hodson D., Marcus R. et al. The biphasic transmittance waveform: an early marker of sepsis in patients with neutropenia. Thromb Haemost 2008;100:146–8.

12. Toh C.H. , Samis J., Downey C. et al. Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca(++)-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation. Blood 2002;100:2522–9.

13. Curvers J ., Thomassen M.C., Nicolaes G.A. et al. Acquired APC resistance and oral contraceptives: differences between two functional tests. Br J Haematol 1999;105:88–94.

14. Park M.S., Martini W.Z., Dubick M.A. et al. Thromboelastography as a better indicator of hypercoagulable state after injury than prothrombin time or activated partial thromboplastin time. J Trauma 2009;67: 266–75.

15. Schreiber M .A., Differding J., Thorborg P. et al. Hypercoagulability is most prevalent early after injury and in female patients. J Trauma 2005;58:475–80.

16. Kaufmann C.R ., Dwyer K.M., Crews J.D. et al. Usefulness of thrombelastography in assessment of trauma patient coagulation. J Trauma 1997;42:716–20.

17. Kim H.K., Kim J.E., Park S.H. et al. High coagulation factor levels and low protein C levels contribute to enhanced thrombin generation in patients with diabetes who do not have macrovascular complications. J Diabetes Complications 2014;28:365–9.

18. Tripodi A., Br anchi A., Chantarangkul V. et al. Hypercoagulability in patients with type

19. diabetes mellitus detected by a thrombin generation assay. J Thromb Thrombolysis 2011;31:165–72.

20. Toukh M., Sieme ns D.R., Black A. et al. Thromboelastography identifies hypercoagulability and predicts thromboembolic complications in patients with prostate cancer. Thromb Res 2014;133:88–95.

21. Hammerova L., Ch abada J., Drobny J., Batorova A. Longitudinal evaluation of markers of hemostasis in pregnancy. Bratisl Lek Listy 2014;115:140–4.

22. Othman M., Falcon B.J., Kadir R. Global hemostasis in pregnancy: are we using thromboelastography to its full potential? Semin Thromb Hemost 2010;36:738–46.

23. Hemker H.C., Wield ers S., Kessels H., Beguin S. Continuous registration of thrombin generation in plasma, its use for the determination of the thrombin potential. Thromb Haemost 1993;70:617–24.

24. Mann K.G., Brummel K., Butenas S. What is all that thrombin for? J Thromb Haemost 2003;1:1504–14.

25. Tripodi A., Legnani C., Chantarangkul V. et al. High thrombin generation measured in the presence of thrombomodulin is associated with an increased risk of recurrent venous thromboembolism. J Thromb Haemost 2008;6:1327–33.

26. Besser M., Baglin C., Luddington R. et al. High rate of unprovoked recurrent venous

27. thrombosis is associated with high thrombingenerating potential in a prospective cohort study. J Thromb Haemost 2008;6:1720–5.

28. Hron G., Kollars M., B inder B.R. et al. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 2006;296:397–402.

29. van Hylckama Vlieg A., Christiansen S.C., Luddington R. et al. Elevated endogenous thrombin potential is associated with an increased risk of a first deep venous thrombosis but not with the risk of recurrence. Br J Haematol 2007;138:769–74.

30. Chaireti R., Jennersjo C ., Lindahl T.L. Is thrombin generation at the time of an acute thromboembolic episode a predictor of recurrence? The LInkoping Study on Thrombosis (LIST) – a 7-year follow-up. Thromb Res 2013;131:135–9.

31. Faber C.G., Lodder J., Ke ssels F., Troost J. Thrombin generation in platelet-rich plasma as a tool for the detection of hypercoagulability in young stroke patients. Pathophysiol Haemost Thromb 2003;33:52–8.

32. Carcaillon L., Alhenc-Gela s M., Bejot Y. et al. Increased thrombin generation is associated

33. with acute ischemic stroke but not with coronary heart disease in the elderly: the Three-City cohort study. Arterioscler Thromb Vasc Biol 2011;31:1445–51.

34. Castoldi E., Simioni P., To rmene D. et al. Differential effects of high prothrombin levels on thrombin generation depending on the cause of the hyperprothrombinemia. J Thromb Haemost 2007;5:971–9.

35. Alhenc-Gelas M., Canonico M. , Picard V. Influence of natural SERPINC1 mutations on ex vivo thrombin generation. J Thromb Haemost 2010;8:845–8.

36. Simioni P., Castoldi E., Lung hi B. et al. An underestimated combination of opposites resulting in enhanced thrombotic tendency. Blood 2005;106:2363–5.

37. Castoldi E., Maurissen L.F., T ormene D. et al. Similar hypercoagulable state and thrombosis risk in type I and type III protein S-deficient individuals from families with mixed type I/III protein S deficiency. Haematologica 2010;95:1563–71.

38. Tchaikovski S.N., van Vliet H.A ., Thomassen M.C. et al. Effect of oral contraceptives on thrombin generation measured via calibrated automated thrombography. Thromb Haemost

39. ;98:1350–6.

40. Ay C., Dunkler D., Simanek R. et al. Prediction of venous thromboembolism in patients with cancer by measuring thrombin generation: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2011;29:2099–103.

41. McLean K.C., Bernstein I.M., Brummel-Ziedins K.E. Tissue factor-dependent thrombin generation across pregnancy. Am J Obstet Gynecol 2012;207:131–6.

42. Rosenkranz A., Hiden M., Leschnik B. et al. Calibrated automated thrombin generation in normal uncomplicated pregnancy. Thromb Haemost 2008;99: 331–7.40. Joly B., Barbay V., Borg J.Y., Le C am-Duchez V. Comparison of markers of coagulation activation and thrombin generation test in uncomplicated pregnancies. Thromb Res 2013;132:386–91.

43. Debaugnies F., Azerad M.A., Noubouos sie D. et al. Evaluation of the procoagulant activity in the plasma of cancer patients using a thrombin generation assay. Thromb Res 2010;126:531–5.

44. Ollivier V., Wang J., Manly D. et al. Detection of endogenous tissue factor levels in plasma using the calibrated automated thrombogram assay. Thromb Res 2010;125: 90–6.

45. Dielis A.W., Castoldi E., Spronk H.M. et al. Coagulation factors and the protein C system as determinants of thrombin generation in a normal population. J Thromb Haemost 2008;6:125–31.

46. van Veen J.J., Gatt A., Cooper P.C. et al. Corn trypsin inhibitor in fluorogenic thrombingeneration measurements is only necessary at low tissue factor concentrations and

47. influences the relationship between factor VIII coagulant activity and thrombogram parameters. Blood Coagul Fibrinolysis 2008;19:183–9.

48. Dargaud Y., Trzeciak M.C., Bordet J.C. e t al. Use of calibrated automated thrombinography +/– thrombomodulin to recognise the prothrombotic phenotype. Thromb Haemost 2006;96:562–7.

49. Ninivaggi M., Apitz-Castro R., Dargaud Y. et al. Whole-blood thrombin generation monitored with a calibrated automated thrombogram-based assay. Clin Chem 2012;58:1252–9.

50. Hincker A., Feit J., Sladen R.N., Wagener G. Rotational thromboelastometry predicts thromboembolic complications after major non-cardiac surgery. Crit Care 2014;18:549.

51. Dai Y., Lee A., Critchley L.A., White P.F. Does thromboelastography predict postoperative thromboembolic events? A systematic review of the literature. Anesth Analg 2009;108:734–42.

52. Yao X., Dong Q., Song Y.et al. Thrombelasto graphy Maximal Clot Strength Could Predict One-Year Functional Outcome in Patients with Ischemic Stroke. Cerebrovasc Dis 2014;38:182–90.

53. Kashuk J.L., Moore E.E., Sabel A. et al. Rap id thrombelastography (r-TEG) identifies hypercoagulability and predicts thromboembolic events in surgical patients. Surgery 2009;146:764–72.

54. McCrath D.J., Cerboni E., Frumento R.J. et al . Thromboelastography maximum amplitude predicts postoperative thrombotic complications including myocardial infarction. Anesth Analg 2005;100:1576–83.

55. Kang Y.G., Martin D.J., Marquez J. et al. Int raoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation. Anesth Analg 1985;64:888–96.

56. Francis J.L., Francis D.A., Gunathilagan G.J. A ssessment of hypercoagulability in patients with cancer using the Sonoclot Analyzer and thromboelastography. Thromb Res 1994;74:335–46.

57. Akay O.M., Ustuner Z., Canturk Z. et al. Laborato ry investigation of hypercoagulability in cancer patients using rotation thrombelastography. Med Oncol 2009;26:358–64.

58. Spiezia L., Marchioro P., Radu C. et al. Whole bl ood coagulation assessment using rotation thrombelastogram thromboelastometry in patients with acute deep vein thrombosis. Blood Coagul Fibrinolysis 2008;19:355–60.

59. Koopman K., Uyttenboogaart M., Hendriks H.G. et al . Thromboelastography in patients with cerebral venous thrombosis. Thromb Res 2009;124:185–8.

60. O'Donnell J., Riddell A., Owens D. et al. Role of t he Thrombelastograph as an adjunctive test in thrombophilia screening. Blood Coagul Fibrinolysis 2004;15:207–11.

61. Miall F.M., Deol P.S., Barnes T.A. et al. Coagulatio n status and complications of pregnancy. Thromb Res 2005;115:461–7.

62. Della Rocca G., Dogareschi T., Cecconet T. et al. Coa gulation assessment in normal pregnancy: thrombelastography with citrated non activated samples. Minerva Anestesiol 2012;78:1357–64.

63. Sharma S.K., Philip J., Wiley J. Thromboelastographic changes in healthy parturients and postpartum women. Anesth Analg 1997;85:94–8.

64. Steer P.L., Krantz H.B. Thromboelastography and Sonoclo t analysis in the healthy parturient. J Clin Anesth 1993;5:419–24.

65. Evans P.A., Hawkins K., Lawrence M. et al. Rheometry and associated techniques for blood coagulation studies. Med Eng Phys 2008;30:671–9.

66. Antovic A. The overall hemostasis potential: a laboratory tool for the investigation of global hemostasis. Semin Thromb Hemost 2010;36:772–9.

67. Matsumoto T., Nogami K., Shima M. Simultaneous measurement of thrombin and plasmin generation to assess the interplay between coagulation and fibrinolysis. Thromb Haemost 2013;110:761–8.

68. Simpson M.L., Goldenberg N.A., Jacobson L.J. et al. Simulta neous thrombin and plasmin generation capacities in normal and abnormal states of coagulation and fibrinolysis in children and adults. Thromb Res 2011;127:317–23.

69. Fadeeva O.A., Panteleev M.A., Karamzin S.S. et al. Thrombopl astin immobilized on polystyrene surface exhibits kinetic characteristics close to those for the native protein and activates in vitro blood coagulation similarly to thromboplastin on fibroblasts. Biochemistry (Mosc) 2010;75:734–43.

70. Dashkevich N.M., Ovanesov M.V., Balandina A.N. et al. Thrombi n activity propagates in space during blood coagulation as an excitation wave. Biophys J 2012;103:2233–40.

71. Ovanesov M.V., Ananyeva N.M., Panteleev M.A. et al. Initiation and propagation of coagulation from tissue factorbearing cell monolayers to plasma: initiator cells do not regulate spatial growth rate. J Thromb Haemost 2005;3:321–31.

72. Panteleev M.A., Ovanesov M.V., Kireev D.A. et al. Spatial propa gation and localization of blood coagulation are regulated by intrinsic and protein C pathways, respectively. Biophys J 2006;90:1489–500.

73. Lipets E., Vlasova O., Urnova E. et al. Circulating contact-path way-activating microparticles together with factors IXa and XIa induce spontaneous clotting in plasma of hematology and cardiologic patients. PLoS One 2014;9:e87692.

74. Dashkevich N.M., Vuimo T.A., Ovsepyan R.A. et al. Effect of pre- analytical conditions on the thrombodynamics assay. Thromb Res 2014;133:472–6.

75. Soshitova N.P., Karamzin S.S., Balandina A.N. et al. Predicting p rothrombotic tendencies in sepsis using spatial clot growth dynamics. Blood Coagul Fibrinolysis 2012;23:498–507.

76. Urnova E.S., Pokrovskaia O.S., Gracheva M.A. et al. [Hypercoagulat ion syndrome in multiple myeloma]. Ter Arkh 2014;86:73–9.

77. Seregina E.A., Nikulina O.F., Tsvetaeva N.V. et al. Laboratory test s for coagulation system monitoring in a patient with beta-thalassemia. Int J Hematol 2014;99:588–96.

78. Westein E., de Witt S., Lamers M. et al. Monitoring in vitro thrombu s formation with novel microfluidic devices. Platelets 2012;23:501–9.

79. Gorog D.A., Kovacs I.B. Thrombotic status analyser. Measurement of pl atelet-rich thrombus formation and lysis in native blood. Thromb Haemost 1995;73:514–20.

80. Shechter M., Merz C.N., Paul-Labrador M.J., Kaul S. Blood glucose and platelet-dependent thrombosis in patients with coronary artery disease. J Am Coll Cardiol 2000;35:300–7.

81. Suades R., Padro T., Vilahur G., Badimon L. Circulating and platelet-de rived microparticles in human blood enhance thrombosis on atherosclerotic plaques. Thromb Haemost 2012;108:1208–19.

82. Roest M., Reininger A., Zwaginga J.J. Flow chamber-based assays to measure thrombus formation in vitro: requirements for standardization. J Thromb Haemost 2011;9:2322–4.

83. Dargaud Y., Wolberg A.S., Luddington R. et al. Evaluation of a standardiz ed protocol for thrombin generation measurement using the calibrated automated thrombogram: an international multicentre study. Thromb Res 2012;130:929–34.

84. Loeffen R., Kleinegris M.C., Loubele S.T. et al. Preanalytic variables of thrombin generation: towards a standard procedure and validation of the method. J Thromb Haemost 2012;10:2544–54.

85. Woodle S.A., Shibeko A.M., Lee T.K., Ovanesov M.V. Determining the impact of instrument variation and automated software algorithms on the TGT in hemophilia and normalized plasma. Thromb Res 2013;132:374–80.