DOI QR코드

DOI QR Code

Benefits of Thromboelastography and Thrombin Generation Assay for Bleeding Prediction in Patients With Thrombocytopenia or Hematologic Malignancies

  • Kim, Seon Young (Department of Laboratory Medicine, Seoul National University College of Medicine) ;
  • Gu, Ja Yoon (Department of Laboratory Medicine, Seoul National University College of Medicine) ;
  • Yoo, Hyun Ju (Department of Laboratory Medicine, Seoul National University College of Medicine) ;
  • Kim, Ji-Eun (Department of Laboratory Medicine, Seoul National University College of Medicine) ;
  • Jang, Seonpyo (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Choe, Sooyeon (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Koh, Youngil (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Kim, Inho (Department of Internal Medicine, Seoul National University College of Medicine) ;
  • Kim, Hyun Kyung (Department of Laboratory Medicine, Seoul National University College of Medicine)
  • Received : 2017.01.03
  • Accepted : 2017.07.10
  • Published : 2017.11.01

Abstract

Background: Thromboelastography (TEG) provides comprehensive information on the whole blood clot formation phases, whereas thrombin generation assay (TGA) reveals the endogenous thrombin levels in plasma. We investigated the potential significance of TEG and TGA parameters for prediction of clinical bleeding in hematologic patients on the basis of the patient's platelet levels. Methods: TEG and TGA were performed in 126 patients with thrombocytopenia or hematologic malignancies. The bleeding tendencies were stratified on the basis of the World Health Organization bleeding grade. Results: Maximum amplitude (MA) and clot formation in TEG and endogenous thrombin potential (ETP) in TGA showed significant associations with high bleeding grades (P =0.001 and P =0.011, respectively). In patients with platelet counts ${\leq}10{\times}10^9/L$, low MA values were strongly associated with a high bleeding risk. For bleeding prediction, the area under the curve (AUC) of MA (0.857) and ETP (0.809) in patients with severe thrombocytopenia tended to be higher than that of platelets (0.740) in all patients. Patients with platelet counts ${\leq}10{\times}10^9/L$ displayed the highest AUC of the combined MA and ETP (0.929). Conclusions: Both TEG and TGA were considered to be good predictors of clinical bleeding in patients with severe thrombocytopenia. Combination of the ETP and MA values resulted in a more sensitive bleeding risk prediction in those with severe thrombocytopenia.

Acknowledgement

Supported by : NRF, SNUH

References

  1. DeLoughery TG. Management of acquired bleeding problems in cancer patients. Hematol Oncol Clin North Am 2010;24:603-24. https://doi.org/10.1016/j.hoc.2010.03.008
  2. Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010;115:168-86. https://doi.org/10.1182/blood-2009-06-225565
  3. Estcourt LJ, Stanworth SJ, Harrison P, Powter G, McClure M, Murphy MF, et al. Prospective observational cohort study of the association between thromboelastometry, coagulation and platelet parameters and bleeding in patients with haematological malignancies- the ATHENA study. Br J Haematol 2014;166:581-91. https://doi.org/10.1111/bjh.12928
  4. Slichter SJ. Relationship between platelet count and bleeding risk in thrombocytopenic patients. Transfus Med Rev 2004;18:153-67. https://doi.org/10.1016/j.tmrv.2004.03.003
  5. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011;117:4190-207. https://doi.org/10.1182/blood-2010-08-302984
  6. Greene LA, Chen S, Seery C, Imahiyerobo AM, Bussel JB. Beyond the platelet count: immature platelet fraction and thromboelastometry correlate with bleeding in patients with immune thrombocytopenia. Br J Haematol 2014;166:592-600. https://doi.org/10.1111/bjh.12929
  7. Zia AN, Chitlur M, Rajpurkar M, Ozgonenel B, Lusher J, Callaghan JH, et al. Thromboelastography identifies children with rare bleeding disorders and predicts bleeding phenotype. Haemophilia 2015;21:124-32. https://doi.org/10.1111/hae.12481
  8. Gunduz E, Akay OM, Bal C, Gulbas Z. Can thrombelastography be a new tool to assess bleeding risk in patients with idiopathic thrombocytopenic purpura? Platelets 2011;22:516-20. https://doi.org/10.3109/09537104.2011.571317
  9. Tran HT, Tjonnfjord GE, Holme PA. Use of thromboelastography and thrombin generation assay to predict clinical phenotype in patients with severe FVII deficiency. Haemophilia 2014;20:141-6. https://doi.org/10.1111/hae.12256
  10. Green D. Management of bleeding complications of hematologic malignancies. Semin Thromb Hemost 2007;33:427-34. https://doi.org/10.1055/s-2007-976178
  11. Kitchens CS. To bleed or not to bleed? Is that the question for the PTT? J Thromb Haemost 2005;3:2607-11. https://doi.org/10.1111/j.1538-7836.2005.01552.x
  12. Al Dieri R, Peyvandi F, Santagostino E, Giansily M, Mannucci PM, Schved JF, et al. The thrombogram in rare inherited coagulation disorders: its relation to clinical bleeding. Thromb Haemost 2002;88:576-82. https://doi.org/10.1055/s-0037-1613258
  13. Dargaud Y, Beguin S, Lienhart A, Al Dieri R, Trzeciak C, Bordet JC, et al. Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B. Thromb Haemost 2005;93:475-80. https://doi.org/10.1160/TH04-10-0706
  14. Kim SY, Kim JE, Kim HK, Kim I, Yoon SS, Park S. Influence of coagulation and anticoagulant factors on global coagulation assays in healthy adults. Am J Clin Pathol 2013;139:370-9. https://doi.org/10.1309/AJCPC5C4AGFRDKMX
  15. Josephson CD, Granger S, Assmann SF, Castillejo MI, Strauss RG, Slichter SJ, et al. Bleeding risks are higher in children versus adults given prophylactic platelet transfusions for treatment-induced hypoproliferative thrombocytopenia. Blood 2012;120:748-60. https://doi.org/10.1182/blood-2011-11-389569
  16. Hemker HC, Giesen P, Al Dieri R, Regnault V, de Smedt E, Wagenvoord R, et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003;33:4-15. https://doi.org/10.1159/000071636
  17. Hanley JA and McNeil BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 1983;148:839-43. https://doi.org/10.1148/radiology.148.3.6878708
  18. Holly P, Lisa L, Plamenova I, Dobrotova M, Kubisz P. Recombinant activated factor VII as an additional agent in the management of bleeding in patients with chemotherapy-induced thrombocytopenia. Blood Transfus 2013;11:466-8.
  19. Gerotziafas GT, Chakroun T, Depasse F, Arzoglou P, Samama MM, Elalamy I. The role of platelets and recombinant factor VIIa on thrombin generation, platelet activation and clot formation. Thromb Haemost 2004;91:977-85. https://doi.org/10.1160/TH03-10-0638
  20. Nielsen VG, Cohen BM, Cohen E. Effects of coagulation factor deficiency on plasma coagulation kinetics determined via thrombelastography: critical roles of fibrinogen and factors II, VII, X and XII. Acta Anaesthesiol Scand 2005;49:222-31. https://doi.org/10.1111/j.1399-6576.2005.00602.x