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Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2019; 18: 112-119

Функциональная активность тромбоцитов: физиология и методы лабораторной диагностики

Пономаренко Е. А., Игнатова А. А., Федорова Д. В., Жарков П. А., Пантелеев М. А.

https://doi.org/10.24287/1726-1708-2019-18-3-112-119

Аннотация

Тромбоциты выполняют многочисленные важные функции не только в процессах нормального функционирования системы гемостаза, но и в других физиологических процессах: регуляции целостности сосудистой стенки, регенерации повреждений, воспалительном ответе. Нарушение их работоспособности происходит при многих заболеваниях и состояниях (включая онкогематологические, воспалительные, аутоиммунные заболевания, солидные опухоли, сепсис), провоцируется травмами, лекарственными препаратами и может вести к опасным последствиям – кровоизлияниям и тромбозам. Однако инструменты для оценки функциональной активности тромбоцитов крайне ограничены, да и представление о том, что такое функциональная активность тромбоцита, не достаточно четкое. В данном обзоре рассмотрены функции тромбоцитов, их нарушения, возможности их оценки существующими методами, а также перспективные направления их развития.

Список литературы

1. Athale U.H., Chan A. Hemorrhagic complications in pediatric hematologic malignancies. Semin Thromb Hemost 2007; 33 (4): 408–15.

2. Yaguchi A., Lobo F.L., Vincent J.L., Pradier O. Platelet function in sepsis. J Thromb Haemost 2004; 2 (12): 2096–102.

3. Ramsey M.T., Fabian T.C., Shahan C.P., Sharpe J.P., Mabry S.E., Weinberg J.A., et al. A prospective study of platelet function in trauma patients. J Trauma Acute Care Surgery 2016; 80 (5): 726–33.

4. Balashova E., Koltsova E., Ignatova A., Polokhov D., Kuprash A., Kirtbaya A., et al. Laboratory Parameters of Blood Coagulation and Platelet Functional Activity in Premature Neonates. Am J Perinatol 2016; 33: A015.

5. Panteleev M.A., Dashkevich N.M., Ataullakhanov F. Hemostasis and throm-bosis beyond biochemistry: roles of geo-metry, flow and diffusion. Thromb Res 2015; 136 (4) 699–711.

6. Rodvien R., Mielke C.H. Role of Platelets in Hemostasis and Thrombosis. West J Med 1976; 125 (3): 181–6.

7. Yoo S.Y., Kwon S.M. Angiogenesis and its therapeutic opportunities. Mediat Inflammation 2013; 1.

8. Thachil J. Platelets in Inflammatory Disorders: A Pathophysiological and Clinical Perspective. Semin Thromb Hemost 2015; 41 (6): 572–81.

9. Walsh T.G., Metharom P., Berndt M. The functional role of platelets in the regulation of angiogenesis. Platelets 2015; 26 (3): 199–11.

10. Ruggeri Z. Mechanisms initiating platelet thrombus formation. Thromb Haemost 1997; 78 (1): 611–6.

11. Ruggeri Z. The role of von Willebrand factor in thrombus formation. Thromb Res 2007; 120 (Suppl 1): S5–9.

12. Nieswandt B., Brakebusch C., Bergmeier W., Schulte V., Bouvard D., Mokhtari-Nejad R., et al. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen. EMBO J 2001; 20 (9): 2120–30.

13. Hou Y., Carrim N., Wang Y., Gallant R.C., Marshall A., Ni H. Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis. J Biomed Res 2015; 30: 29.

14. Golino P., Crea F., Willerson J. How to study the effects of platelet aggregation and thrombosis on coronary vasomotion and their clinical relevance. Ital Hear J 2002; 3 (4): 220–5.

15. Podoplelova N.A., Sveshnikova A.N., Kurasawa J.H., Sarafanov A.G., Chambost H., Vasil’ev S.A., et al. Hysteresis-like binding of coagulation factors X/Xa to procoagulant activated platelets and phospholipids results from multistep association and membrane-dependent multimerization. Biochim Biophys Acta 2016; 1858 (6): 1216–27.

16. Abaeva A.A., Canault M., Kotova Y.N., Obydennyy S.I., Yakimenko A.O., Podoplelova N.A., et al. Procoagulant platelets form an -granule protein-covered “cap” on their surface that promotes their attachment to aggregates. J Biol Chem 2013; 288 (41): 29621–32.

17. Zakharova N.V., Artemenko E.O., Podoplelova N.A., Sveshnikova A.N., Demina I.A., Ataullakhanov F.I., et al. Platelet surface-associated activation and secretion-mediated inhibition of coagulation factor XII. PLoS One 2015; 20 (1): e0116665.

18. Clemetson K. Platelets and primary haemostasis. Thromb Res Elsevier Ltd 2012; 129 (3): 220–4.

19. Brass L.F., Tomaiuolo M., Stalker T. Harnessing the platelet signaling network to produce an optimal hemostatic response. Hematol Oncol Clin North Am 2013; 27 (3): 381–09.

20. Varga-Szabo D., Pleines I., Nieswandt B. Cell adhesion mechanisms in platelets. Arter Thromb Vasc Biol 2008; 28 (3): 403–12.

21. Nurden A.T., Freson K., Seligsohn U. Inherited platelet disorders. Haemophilia 2012; 18 (Suppl 4): 154–60.

22. Luu S., Gardiner E.E., Andrews R. Bone Marrow Defects and Platelet Function: A Focus on MDS and CLL. Cancers (Basel) 2018; 10 (5): pii: E147.

23. Winqvist M., Asklid A., Andersson P.O., Karlsson K., Karlsson C., Lauri B., et al. Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group. Haematologica 2016; 101 (12): 1573–80.

24. Bye A.P., Unsworth A.J., Vaiyapuri S., Stainer A.R., Fry M.J., Gibbins J. Ibrutinib Inhibits Platelet Integrin IIb3 Outside-In Signaling and Thrombus Stability But Not Adhesion to Collagen. Arter Thromb Vasc Biol 2015; 35 (11): 2326–35.

25. Levade M., David E., Garcia C., Laurent P.A., Cadot S., Michallet A.S., et al. Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions. Blood 2024; 124 (26): 3991–5.

26. Born G. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927–9.

27. Gadisseur A., Hermans C., Berneman Z., Schroyens W., Deckmyn H., Michiels J. Laboratory diagnosis and molecular classification of von Willebrand disease. Acta Haematol 2009; 121 (2–3): 71–84.

28. Jennings L.K., McCabe White M. Platelet aggregation. Platelets/ed. Michelson. Boston: Academic Press, 2007, 495–507.

29. Филиппова О.И., Колосков А.В., Столица А.А. Методы исследования функциональной активности тромбоцитов (обзор литературы). Трансфузиология 2012; 13: 493–514.

30. Chan M.V., Armstrong P.C.J., Papalia F., Kirkby N.S., Warner T. Optical multi-channel (optimul) platelet aggregometry in 96-well plates as an additional method of platelet reactivity testing. Platelets 2011; 22 (7): 485–94.

31. Armstrong P.C., Leadbeater P.D., Chan M.V., Kirkby N.S., Jakubowski J.A., Mitchell J.A., et al. In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation. J Thromb Haemost 2011; 9 (3): 552–61.

32. Cattaneo M., Hayward C.P., Moffat K.A., Pugliano M.T., Liu Y., Michelson A. Results of a worldwide survey on the assessment of platelet function by light transmission aggregometry: a report from the platelet physiology subcommittee of the SSC of the ISTH. J Thromb Haemost 2009; 7 (6): 1029.

33. Cardinal D.C., Flower R. The electronic aggregometer: a novel device for asse-ssing platelet behavior in blood. J Pharmacol Methods 1980; 3 (2): 135–58.

34. Smith J.W., Steinhubl S.R., Lincoff A.M., Coleman J.C., Lee T.T., Hillman R.S., et al. Rapid platelet-function assay: an automated and quantitative cartridge-based method. Circulation 1999; 99 (5): 620–5.

35. Campbell J., Ridgway H., Carville D. Plateletworks: a novel point of care platelet function screen. Mol Diagn Ther 2008; 12 (4): 253–8.

36. Lennon M.J., Gibbs N.M., Weightman W.M., McGuire D., Michalopoulos N. A comparison of Plateletworks and platelet aggregometry for the assessment of aspirin-related platelet dysfunction in cardiac surgical patients. J Cardiothorac Vasc Anesth 2004; 18 (2): 136–40.

37. Craft R.M., Chavez J.J., Snider C.C., Muenchen R.A., Carroll R. Comparison of modified Thrombelastograph and Plateletworks whole blood assays to optical platelet aggregation for monitoring reversal of clopidogrel inhibition in elective surgery patients. J Lab Clin Med 2005; 145 (6): 309–15.

38. Favaloro E.J., Mohammed S. Platelet function testing: auditing local practice and broader implications. Clin Lab Sci 2010; 23 (1): 21–31.

39. Hayward C.P., Harrison P., Cattaneo M., Ortel T.L., Rao A.K. Platelet Physiology Subcommittee of the Scientific and Standartization Committee of the International Society of Thrombosis and Haemostasis. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost 2006; 4 (2): 312–9.

40. Homoncik M., Jilma B., Hergovich N., Stohlawetz P., Panzer S., Speiser W. Monitoring of aspirin (ASA) pharmacodynamics with the platelet function analyzer PFA-100. Thromb Haemost 2000; 83 (2): 316–21.

41. Varon D., Dardik R., Shenkman B., Kotev-Emeth S., Farzame N., Tamarin I., et al. A new method for quantitative analysis of whole blood platelet interaction with extracellular matrix under flow conditions. Thromb Res 1997; 85 (4): 283–94.

42. Sakariassen K.S., Hanson S.R., Cadroy Y. Methods and models to evaluate shear-dependent and surface reactivity-dependent antithrombotic efficacy. Thromb Res 2001; 104 (3): 149–74.

43. Heemskerk J.W., Sakariassen K.S., Zwaginga J.J., Brass L.F., Jackson S.P., Farndale R.W., et al. Collagen surfaces to measure thrombus formation under flow: possibilities for standardization. J Thromb Haemost 2011; 9 (4): 856–8.

44. Cosemans J.M., Kuijpers M.J., Lecut C., Loubele S.T., Heeneman S., Jandrot-Perrus M., et al. Contribution of platelet glycoprotein VI to the thrombogenic effect of collagens in fibrous atherosclerotic lesions. Atherosclerosis 2005; 181 (1): 19–27.

45. Jackson S.P., Nesbitt W.S., Westein E. Dynamics of platelet thrombus forma-tion. J Thromb Haemost 2009: 7 (Suppl 1): 17–20.

46. Cosemans J.M., Iserbyt B.F., Deckmyn H., Heemskerk J. Multiple ways to switch platelet integrins on and off. J Thromb Haemost 2008; 6 (8): 1253–61.

47. Jackson S. The growing complexity of platelet aggregation. Blood 2007; 109 (12): 5087–95.

48. Roest M., Reininger A., Zwaginga J.J., King M.R., Heemskerk J.W. Biorheology Subcomittee of the SSC of the ICTH. Flow chamber-based assays to mea-sure thrombus formation in vitro: requirements for standardization. J Thromb Haemost 2011; 9 (11): 2322–4.

49. Van Kruchten R., Cosemans J.M., Heemskerk J. Measurement of whole blood thrombus formation using parallel-plate flow chambers – a practical guide. Platelets 2012: 23 (3): 229–42.

50. Сироткина О.В., Боганькова Н.А., Ласковец А.Б., Кухарчик Г.А., Гайковая Л.Б., Вавилова Т.В. Иммунологические методы в оценке функциональной активности тромбоцитов у больных с сердечно-сосудистыми заболеваниями. Медицинская иммунология 2010: 12 (3): 213–8.

51. Brown M., Wittwer C. Flow cytometry: principles and clinical applications in hematology. Clin Chem 2000; 46 (8, рt. 2): 1221–9.

52. Södergren A.L., Ramström S. Platelet subpopulations remain despite strong dual agonist stimulation and can be characterised using a novel six-colour flow cytometry protocol. Sci Rep 2018; 8 (1): 1441.

53. Michelson A.D., Barnard M.R., Krueger L.A., Frelinger A.L. 3rd F.M. Evaluation of platelet function by flow cytometry. Methods 2000; 21 (3): 259–70.

54. Rochat S., Alberio L. Formaldehyde-fixation of platelets for flow cytometric measurement of phosphatidylserine exposure is feasible. Cytom A 2015; 87 (1): 32–6.

55. Ignatova A.A., Ponomarenko E.A., Polo-khov D.M., Suntsova E.V., Zharkov P.A., Fedorova D.V., et al. Flow cytometry for pediatric platelets. Platelets 2018; 4: 1–10.

56. Федорова Д.В., Жарков П.А., Игнатова A.А., Федотов А.Ю., Полохов Д.М., Полетаев А.В. и соавт. Диагностика тромбоцитопатий у детей: корреляции исследования функциональной активности тромбоцитов с клинической картиной и результатами агрегометрии. Вопросы гематологии/онкологии и иммунопатологии в педиатрии 2018; 17 (1): 16–22.

57. Жарков П.А., Демина И.А., Пантелеев М.А. Использование метода функциональной активности тромбоцитов для диагностики тромбоцитопатий у детей. Вопросы гематологии/онкологии и иммунопатологии в педиатрии 2016; 15 (2): 40–6.

58. Suntsova E.V., Demina I.M., Ignatova A.A., Ershov N.M., Trubina N.M., Dobrynina J., et al. Bleeding tendency and platelet function during treatment with romiplostim in children with severe immune thrombocytopenic purpura. Int J Hematol 2017; 105 (6): 841–8.

59. Ignatova A.A., Karpova O.V., Trakhtman P.E., Rumiantsev S.A., Panteleev M.A. Functional characteristics and clinical effectiveness of platelet concentrates treated with riboflavin and ultraviolet light in plasma and in platelet additive solution. Vox Sang 2016; 110 (3): 244–52.

Pediatric Hematology/Oncology and Immunopathology. 2019; 18: 112-119

Platelet functional activity: physiology and laboratory diagnostic methods

Ponomarenko E. A., Ignatova A. A., Fedorova D. V., Zharkov P. A., Panteleev M. A.

https://doi.org/10.24287/1726-1708-2019-18-3-112-119

Abstract

Platelets perform numerous important functions not only in the process of normal functioning of hemostatic system, but also in other physiological processes, such as: vessel wall integrity regulation, wound healing, inflammatory response. Its malfunction can be found in various diseases and conditions (including oncohematological disorders, solid tumors, inflammatory diseases, sepsis, autoimmune disorders), is triggered by injury or medications and can lead to dangerous consequences, such as bleeding and thrombosis. However, platelets functional activity quantity assessment tools are extremely limited, the perception what platelet functional activity is about is also quite unclear. This review considers platelets function, its' abnormalities, possibilities for its' assessment by existing methods as well as promising directions for their development.

References

1. Athale U.H., Chan A. Hemorrhagic complications in pediatric hematologic malignancies. Semin Thromb Hemost 2007; 33 (4): 408–15.

2. Yaguchi A., Lobo F.L., Vincent J.L., Pradier O. Platelet function in sepsis. J Thromb Haemost 2004; 2 (12): 2096–102.

3. Ramsey M.T., Fabian T.C., Shahan C.P., Sharpe J.P., Mabry S.E., Weinberg J.A., et al. A prospective study of platelet function in trauma patients. J Trauma Acute Care Surgery 2016; 80 (5): 726–33.

4. Balashova E., Koltsova E., Ignatova A., Polokhov D., Kuprash A., Kirtbaya A., et al. Laboratory Parameters of Blood Coagulation and Platelet Functional Activity in Premature Neonates. Am J Perinatol 2016; 33: A015.

5. Panteleev M.A., Dashkevich N.M., Ataullakhanov F. Hemostasis and throm-bosis beyond biochemistry: roles of geo-metry, flow and diffusion. Thromb Res 2015; 136 (4) 699–711.

6. Rodvien R., Mielke C.H. Role of Platelets in Hemostasis and Thrombosis. West J Med 1976; 125 (3): 181–6.

7. Yoo S.Y., Kwon S.M. Angiogenesis and its therapeutic opportunities. Mediat Inflammation 2013; 1.

8. Thachil J. Platelets in Inflammatory Disorders: A Pathophysiological and Clinical Perspective. Semin Thromb Hemost 2015; 41 (6): 572–81.

9. Walsh T.G., Metharom P., Berndt M. The functional role of platelets in the regulation of angiogenesis. Platelets 2015; 26 (3): 199–11.

10. Ruggeri Z. Mechanisms initiating platelet thrombus formation. Thromb Haemost 1997; 78 (1): 611–6.

11. Ruggeri Z. The role of von Willebrand factor in thrombus formation. Thromb Res 2007; 120 (Suppl 1): S5–9.

12. Nieswandt B., Brakebusch C., Bergmeier W., Schulte V., Bouvard D., Mokhtari-Nejad R., et al. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen. EMBO J 2001; 20 (9): 2120–30.

13. Hou Y., Carrim N., Wang Y., Gallant R.C., Marshall A., Ni H. Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis. J Biomed Res 2015; 30: 29.

14. Golino P., Crea F., Willerson J. How to study the effects of platelet aggregation and thrombosis on coronary vasomotion and their clinical relevance. Ital Hear J 2002; 3 (4): 220–5.

15. Podoplelova N.A., Sveshnikova A.N., Kurasawa J.H., Sarafanov A.G., Chambost H., Vasil’ev S.A., et al. Hysteresis-like binding of coagulation factors X/Xa to procoagulant activated platelets and phospholipids results from multistep association and membrane-dependent multimerization. Biochim Biophys Acta 2016; 1858 (6): 1216–27.

16. Abaeva A.A., Canault M., Kotova Y.N., Obydennyy S.I., Yakimenko A.O., Podoplelova N.A., et al. Procoagulant platelets form an -granule protein-covered “cap” on their surface that promotes their attachment to aggregates. J Biol Chem 2013; 288 (41): 29621–32.

17. Zakharova N.V., Artemenko E.O., Podoplelova N.A., Sveshnikova A.N., Demina I.A., Ataullakhanov F.I., et al. Platelet surface-associated activation and secretion-mediated inhibition of coagulation factor XII. PLoS One 2015; 20 (1): e0116665.

18. Clemetson K. Platelets and primary haemostasis. Thromb Res Elsevier Ltd 2012; 129 (3): 220–4.

19. Brass L.F., Tomaiuolo M., Stalker T. Harnessing the platelet signaling network to produce an optimal hemostatic response. Hematol Oncol Clin North Am 2013; 27 (3): 381–09.

20. Varga-Szabo D., Pleines I., Nieswandt B. Cell adhesion mechanisms in platelets. Arter Thromb Vasc Biol 2008; 28 (3): 403–12.

21. Nurden A.T., Freson K., Seligsohn U. Inherited platelet disorders. Haemophilia 2012; 18 (Suppl 4): 154–60.

22. Luu S., Gardiner E.E., Andrews R. Bone Marrow Defects and Platelet Function: A Focus on MDS and CLL. Cancers (Basel) 2018; 10 (5): pii: E147.

23. Winqvist M., Asklid A., Andersson P.O., Karlsson K., Karlsson C., Lauri B., et al. Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group. Haematologica 2016; 101 (12): 1573–80.

24. Bye A.P., Unsworth A.J., Vaiyapuri S., Stainer A.R., Fry M.J., Gibbins J. Ibrutinib Inhibits Platelet Integrin IIb3 Outside-In Signaling and Thrombus Stability But Not Adhesion to Collagen. Arter Thromb Vasc Biol 2015; 35 (11): 2326–35.

25. Levade M., David E., Garcia C., Laurent P.A., Cadot S., Michallet A.S., et al. Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions. Blood 2024; 124 (26): 3991–5.

26. Born G. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927–9.

27. Gadisseur A., Hermans C., Berneman Z., Schroyens W., Deckmyn H., Michiels J. Laboratory diagnosis and molecular classification of von Willebrand disease. Acta Haematol 2009; 121 (2–3): 71–84.

28. Jennings L.K., McCabe White M. Platelet aggregation. Platelets/ed. Michelson. Boston: Academic Press, 2007, 495–507.

29. Filippova O.I., Koloskov A.V., Stolitsa A.A. Metody issledovaniya funktsional'noĭ aktivnosti trombotsitov (obzor literatury). Transfuziologiya 2012; 13: 493–514.

30. Chan M.V., Armstrong P.C.J., Papalia F., Kirkby N.S., Warner T. Optical multi-channel (optimul) platelet aggregometry in 96-well plates as an additional method of platelet reactivity testing. Platelets 2011; 22 (7): 485–94.

31. Armstrong P.C., Leadbeater P.D., Chan M.V., Kirkby N.S., Jakubowski J.A., Mitchell J.A., et al. In the presence of strong P2Y12 receptor blockade, aspirin provides little additional inhibition of platelet aggregation. J Thromb Haemost 2011; 9 (3): 552–61.

32. Cattaneo M., Hayward C.P., Moffat K.A., Pugliano M.T., Liu Y., Michelson A. Results of a worldwide survey on the assessment of platelet function by light transmission aggregometry: a report from the platelet physiology subcommittee of the SSC of the ISTH. J Thromb Haemost 2009; 7 (6): 1029.

33. Cardinal D.C., Flower R. The electronic aggregometer: a novel device for asse-ssing platelet behavior in blood. J Pharmacol Methods 1980; 3 (2): 135–58.

34. Smith J.W., Steinhubl S.R., Lincoff A.M., Coleman J.C., Lee T.T., Hillman R.S., et al. Rapid platelet-function assay: an automated and quantitative cartridge-based method. Circulation 1999; 99 (5): 620–5.

35. Campbell J., Ridgway H., Carville D. Plateletworks: a novel point of care platelet function screen. Mol Diagn Ther 2008; 12 (4): 253–8.

36. Lennon M.J., Gibbs N.M., Weightman W.M., McGuire D., Michalopoulos N. A comparison of Plateletworks and platelet aggregometry for the assessment of aspirin-related platelet dysfunction in cardiac surgical patients. J Cardiothorac Vasc Anesth 2004; 18 (2): 136–40.

37. Craft R.M., Chavez J.J., Snider C.C., Muenchen R.A., Carroll R. Comparison of modified Thrombelastograph and Plateletworks whole blood assays to optical platelet aggregation for monitoring reversal of clopidogrel inhibition in elective surgery patients. J Lab Clin Med 2005; 145 (6): 309–15.

38. Favaloro E.J., Mohammed S. Platelet function testing: auditing local practice and broader implications. Clin Lab Sci 2010; 23 (1): 21–31.

39. Hayward C.P., Harrison P., Cattaneo M., Ortel T.L., Rao A.K. Platelet Physiology Subcommittee of the Scientific and Standartization Committee of the International Society of Thrombosis and Haemostasis. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost 2006; 4 (2): 312–9.

40. Homoncik M., Jilma B., Hergovich N., Stohlawetz P., Panzer S., Speiser W. Monitoring of aspirin (ASA) pharmacodynamics with the platelet function analyzer PFA-100. Thromb Haemost 2000; 83 (2): 316–21.

41. Varon D., Dardik R., Shenkman B., Kotev-Emeth S., Farzame N., Tamarin I., et al. A new method for quantitative analysis of whole blood platelet interaction with extracellular matrix under flow conditions. Thromb Res 1997; 85 (4): 283–94.

42. Sakariassen K.S., Hanson S.R., Cadroy Y. Methods and models to evaluate shear-dependent and surface reactivity-dependent antithrombotic efficacy. Thromb Res 2001; 104 (3): 149–74.

43. Heemskerk J.W., Sakariassen K.S., Zwaginga J.J., Brass L.F., Jackson S.P., Farndale R.W., et al. Collagen surfaces to measure thrombus formation under flow: possibilities for standardization. J Thromb Haemost 2011; 9 (4): 856–8.

44. Cosemans J.M., Kuijpers M.J., Lecut C., Loubele S.T., Heeneman S., Jandrot-Perrus M., et al. Contribution of platelet glycoprotein VI to the thrombogenic effect of collagens in fibrous atherosclerotic lesions. Atherosclerosis 2005; 181 (1): 19–27.

45. Jackson S.P., Nesbitt W.S., Westein E. Dynamics of platelet thrombus forma-tion. J Thromb Haemost 2009: 7 (Suppl 1): 17–20.

46. Cosemans J.M., Iserbyt B.F., Deckmyn H., Heemskerk J. Multiple ways to switch platelet integrins on and off. J Thromb Haemost 2008; 6 (8): 1253–61.

47. Jackson S. The growing complexity of platelet aggregation. Blood 2007; 109 (12): 5087–95.

48. Roest M., Reininger A., Zwaginga J.J., King M.R., Heemskerk J.W. Biorheology Subcomittee of the SSC of the ICTH. Flow chamber-based assays to mea-sure thrombus formation in vitro: requirements for standardization. J Thromb Haemost 2011; 9 (11): 2322–4.

49. Van Kruchten R., Cosemans J.M., Heemskerk J. Measurement of whole blood thrombus formation using parallel-plate flow chambers – a practical guide. Platelets 2012: 23 (3): 229–42.

50. Sirotkina O.V., Bogan'kova N.A., Laskovets A.B., Kukharchik G.A., Gaikovaya L.B., Vavilova T.V. Immunologicheskie metody v otsenke funktsional'noi aktivnosti trombotsitov u bol'nykh s serdechno-sosudistymi zabolevaniyami. Meditsinskaya immunologiya 2010: 12 (3): 213–8.

51. Brown M., Wittwer C. Flow cytometry: principles and clinical applications in hematology. Clin Chem 2000; 46 (8, rt. 2): 1221–9.

52. Södergren A.L., Ramström S. Platelet subpopulations remain despite strong dual agonist stimulation and can be characterised using a novel six-colour flow cytometry protocol. Sci Rep 2018; 8 (1): 1441.

53. Michelson A.D., Barnard M.R., Krueger L.A., Frelinger A.L. 3rd F.M. Evaluation of platelet function by flow cytometry. Methods 2000; 21 (3): 259–70.

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