Global tests in patients with Ph-negative myeloproliferative neoplasms
https://doi.org/10.35754/0234-5730-2023-68-3-374-381
Abstract
Introduction: A frequent clinical manifestation of Ph-negative myeloproliferative neoplasms (MPN) is the development of thrombosis. To identify the state of hypercoagulation it is relevant and promising to introduce global tests for evaluating the hemostasis — the thrombin generation test (TGT) and thromboelastography (TEG).
Aim: to evaluate the parameters of thrombin generation and thromboelastography in patients with Ph-negative MPN.
Material and methods. In total, 62 patients with MNP were included in the study: 27 with polycythemia vera (PV), 14 with essential thrombocythemia (ET) and 21 with primary myelofibrosis (PMF). The control group included 55 practically healthy individuals, comparable in gender and age (19 people in the study of TEG, 36 people in the study of TGT). The TEG was performed using a “TEG 5000” thromboelastograph. TGT was measured with Calibrated Automated Thrombinography.
Results: Ly30 and Ly60 in TEG in patients were significantly lower (0.35 (0.20–0.48), 0.00 (0.00–0.40) and 0.00 (0.00 — 0.43) and 3.15 (2.45–3.60), 1.25 (0.10–3.58) and 0.60 (0.00–3.05) respectively), than in the control (1.60 (1.05–2.75) and 6.20 (4.15–8.30), respectively), which indicates the ineffectiveness of fibrinolysis. The values of MA and G in patients with ET and PV significantly exceeded the control (69.15 (67.98–70.78) mm and 65.20 (59.65–63.83) mm versus 62.00 (57.75–6.75) mm and 11.20 (10.60–12.15) din/cm2 and 9.40 (7.40–11.60) din/cm2 versus 8.20 (6.85–8.75) din/cm2, respectively. The most pronounced change in sensitivity to TM was observed in patients with ET (27.94 (17.35–43.58) % and 13.29 (-3.48–23.60) %, respectively; p < 0.05). A significant decrease in ETP was observed in patients with PV and PMF.
Conclusion. The study of hemostasis in patients with MPN using TEG and TGT revealed the presence of multidirectional changes associated with the disease. The TEG showed that an increase in the time required for the onset of fibrin formation is combined with increased clot strength and inhibited fibrinolysis, which are risk factors for the development of thromboembolic complications. The study of TGT determined a decrease in the quantitative characteristics of thrombin generation and at the same time the failure of the anticoagulant system of protein C, leading to the development of hypercoagulation.
Keywords
About the Authors
N. N. SilinaRussian Federation
Natalia N. Silina, Cand. Sci. (Med.), Leading Researcher
Research Department of Hemostasis Pathology
191024
St. Petersburg
N. E. Korsakova
Russian Federation
Natalia E. Korsakova, Cand. Sci. (Biol.), Researcher
Research Department of Hemostasis Pathology
191024
St. Petersburg
O. G. Golovina
Russian Federation
Olga G. Golovina, Cand. Sci. (Biol.), Leading Researcher
Research Department of Hemostasis Pathology
191024
St. Petersburg
O. U. Matvienko
Russian Federation
Olesya U. Matvienko, Cand. Sci. (Med.), Leading Researcher
Research Department of Hemostasis Pathology
191024
St. Petersburg
L. R. Tarkovskaya
Russian Federation
Lana R. Tarkovskaya, Cand. Sci. (Biol.), Senior Researcher
Research Department of Hemostasis Pathology
191024
St. Petersburg
E. V. Efremova
Russian Federation
Elizaveta V. Efremova, Hematologist
Research Department of Chemotherapy of Hemoblastoses, Depressions of Hematopoiesis and Bone Marrow Transplantation with the ICU
191024
St. Petersburg
S V. Voloshin
Russian Federation
Sergey V. Voloshin, Cand. Sci. (Med.), Deputy Chief Physician for Medical Work
191024
St. Petersburg
References
1. Abdulkadyrov K. M., Shuvaev V.A., Martynkevich I.S. Modern approaches to the diagnosis and treatment of essential thrombocytemia: literature review and own data. Klinicheskaya onkogematologiya. 2015; 8(3): 235–47 (In Russian).
2. Barbui T., Vannucchi A.M., Guglielmelli P., et al. An agenda for future research projects in polycythemia vera and essential thrombocythemia. Haematologica. 2020; 105(8): 1999–2003. DOI: 10.3324/haematol.2019.246207.
3. Tefferi A. Myeloproliferative neoplasms: A decade of discoveries and treatment advances. Am J Hematol. 2016; 91(1): 50–8. DOI: 10.1002/ajh.24221.
4. Lussana F., Carobbio A., Salmoiraghi S., et al. Driver mutations (JAK2V617F, MPLW515L/K or CALR), pentraxin-3 and C-reactive protein in essential thrombocythemia and polycythemia vera. J Hematol Oncol. 2017; 10: 54–61. DOI: 10.1186/s13045-017-0425-z.
5. Duchemin J., Ugo V., Ianotto J-C., et al. Increased circulating procoagulant activity and thrombin generation in patients with myeloproliferative neoplasms. Thromb Res. 2010; 126: 238–42. DOI: 10.1016/j.thromres.2010.06.025.
6. Dentali F., Pegoraro S., Barco S., et al. Clinical course of isolated distal deep vein thrombosis in patients with active cancer: a multicenter cohort study. J Thromb Haemost. 2017; 15: 1757–63. DOI: 10.1111/jth.13761.
7. Landolfi R., Di Gennaro L. Pathophysiology of thrombosis in myeloproliferative neoplasms. Haematologica. 2011; 96(2): 183–6. DOI: 10.3324/haematol.2010.038299.
8. De Stefano V., Ruggeri M., Cervantes F., et al. High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists. Leukemia. 2016; 30: 2032–8. DOI: 10.1038/leu.2016.85.
9. Hemker H.C., Giesen P., Al Dieri R. et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thrombo. 2003; 33(1): 4–15 DOI: 10.1159/000071636.
10. Efremova O.V., Mamaev A.N., Elykomov V.A., et al. Bleeding and features of thromboelastography indicators in patients with chronic myeloid leukemia. Novosibirskii gosudarstvennyi meditsinskii universitet. 2014; 6: 30 (In Russian).
11. Smirnova O.A. New technologies in the evaluation of replacement therapy for hemophilia. Tromboz, gemostaz i reologiya. 2016; 3(67): 394–5 (In Russian).
12. Barrowcliffe W., Cattaneo M, Podda G.M., et al. New approaches for measuring coagulation. Haemophilia. 2006; 12(3): 76–81. DOI: 10.1111/j.1365-2516.2006.01262.x.
13. Lance M.D. A general review of major global coagulation assays: thromboelastography, thrombin generation test and clot waveform analysis. Thromb J. 2015; 13: 1. DOI: 10.1186/1477-9560-13-1.
14. Arber D.A., Orazi A., Hasserjian R., et al. The 2016 revision of the World Health Organization classifi cation of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20): 2391–405. DOI: 10.1182/blood-2016-03-643544.
15. Lipets E.N., Ataullakhanov F.I., Panteleev M.A. Integral laboratory tests of hemostasis in the diagnosis of hypercoagulation and risk assessment of thrombosis. Onkogematologiya. 2015; 10(3): 73–91 (In Russian). URL: https://oncohematology.abvpress.ru/ongm/article/viewFile/157/171.
16. Brummel-Ziedins K.E., Wolberg A.S. Global assays of hemostasis. Curr Opin Hematol. 2014; 21: 395–403. DOI: 10.1097/MOH.0000000000000074.
17. Dargaud Y., Sorensen B., Shima M., et al. Global haemostasis and point of care testing. Haemophilia. 2012; 18(4): 81–8. DOI: 10.1111/j.1365-2516.2012.02855.x.
18. van Geffen M., van Heerde W.L. Global haemostasis assays, from bench to bedside. Thromb Res. 2012; 129: 681–7. DOI: 10.1016/j.thromres.2011.12.006.
Review
For citations:
Silina N.N., Korsakova N.E., Golovina O.G., Matvienko O.U., Tarkovskaya L.R., Efremova E.V., Voloshin S.V. Global tests in patients with Ph-negative myeloproliferative neoplasms. Russian journal of hematology and transfusiology. 2023;68(3):374-381. (In Russ.) https://doi.org/10.35754/0234-5730-2023-68-3-374-381