Thromboelastometry to assess the effect of low-molecular-weight heparin prophylactic doses: 616.151.55
Тромбоз, гемостаз и реология

Tromboz, Gemostaz I Reologiya
scientific and practical journal

ISSN 2078–1008 (Print); ISSN 2687-1483 (online)

Keywords

Yudin D. V.
Shulutko E. M.
Savushkin A. V. Thromboelastometry to assess the effect of low-molecular-weight heparin prophylactic doses. Tromboz
gemostaz i reologiya. 2024;(4):36–45. (In Russ.).

Abstract

Summary. Aim: to determine the thromboelastometric criteria for screening of prophylactic doses effect of low molecular weight heparins (LMWHs) and to evaluate the possibilities of their use in patients with acquired antithrombin III (AT-III) deficiency. Materials and Methods.
A prospective observational single-center study was conducted. During the first stage, 14 patients without heparin resistance factors (hyperfibrinogenemia and AT-III deficiency) underwent a NATEM thromboelastometry blood sample test without an anticoagulant. Additionally, three blood samples with in vitro nadroparin calcium activity (0.2, 0.3, and 0.4 IU/mL) were collected. During the second stage, the NATEM test was conducted on 45 patients who had undergone liver resections. The test was performed both before and after the prophylactic doses of nadroparin calcium. Fibrinogen concentration and AT-III activity were determined in all patients. The ROC-analysis was performed to determine the sensitivity and specificity of AT-III activity in relation to the upper limits of normal CT and CFT intervals following the use of an anticoagulant. Results. The thromboelastometry parameters observed during the first study stage significantly depended on anti- Xa activity level in vitro. The CT interval was found to exceed the norm in 95.2% of the cases, while the CFT interval exceeded the norm in 90.5%.
The results of the second study stage, in which an anticoagulant with normal AT-III activity was used, demonstrated no significant diffe rence from the initial parameters. During this stage, the CT interval exceeded the norm in 97% of the cases, while the CFT interval exceeded the norm in 90.3%. The correlation between AT-III activity and CT and CFT intervals was 0.401 (p < 0.01) and 0.246 (p < 0.05), respectively. AT-IIIactivity level greater than 50% for a CT interval above the normal upper limit had a sensitivity of 82.28% and a specificity of 71.43%. AT-III activity level of 70% or greater had a sensitivity of 39.24% and a specificity of 92.86%. Conclusion. The upper normal limit of the CT NATEM interval represents the optimal criterion for screening LMWHs effect. Screening will allow identifying patients with a high risk of thrombotic complications and personalizing prevention strategies for venous thromboembolic complications in patients with AT-III deficiency.

For citation: Yudin D. V., Shulutko E. M., Savushkin A. V. Thromboelastometry to assess the effect of low-molecular-weight heparin prophylactic doses. Tromboz, gemostaz i reologiya. 2024;(4):36–45. (In Russ.).

References

  1. Kuznetsova N. K., Klychnikova E. V., Zhuravel S. V. et al. Antithrom bin III in the prevention of thrombotic complications in high risk patients undergoing liver transplantation. Transplantologiya. 2019;11(3):209–17. (In Russ.). DOI: 10.23873/20740506201911 3209217.
  2. Kirienko I. S., Bulanov A.Yu., Simarova I. B., Dzyuba S. V. Experience with the use of Antithrombin III concentrate in a multidisciplinary clinic. Vestnik intensivnoj terapii imeni A. I. Saltanova. 2018;(2):46– 50. (In Russ.). DOI: 10.21320/1818474X201824650.
  3. Croles F. N., BorjasH oward J., Nasserinejad K. et al. Risk of venous thrombosis in antithrombin deficiency: a systematic review and Bayesian metaanalysis. Semin Thromb Hemost. 2018;44(4):315–26. DOI: 10.1055/s00381625983.
  4. Teien A. N., Lie M., Abildgaard U. Assay of heparin in plasma using a chromogenic substrate for activated factor X. Thromb Res. 1976;8(3):413–6. DOI: 10.1016/00493848(76)900347..
  5. Teien A. N., Lie M. Evaluation of an amidolytic heparin assay method: increased sensitivity by adding purified antithrombin III. Thromb Res. 1977;10(3):399–410. DOI: 10.1016/00493848(77 )901505.
  6. Morozov Yu. A. Antithrombin III and effectiveness of traditional antiplatelet therapy. Tromboz, gemostaz i reologiya. 2012;(4):28– 32. (In Russ.).
  7. Vera Aguilera J., Yousef H., Beltran Melgarejo D. et al. Clinical scenarios for discordant anti-Xa. Adv Hematol. 2016;2016:4054806. DOI: 10.1155/2016/4054806.
  8. Gehrie E., Laposata M. Test of the month: The chromogenicantifactor Xa assay. Am J Hematol. 2012;87(2):194–6. DOI: 10.1002/ ajh.22222.
  9. Croles F. N., Lukens M. V., Mulder R. et al. Monitoring of heparins in antithrombin-deficient patients. Thromb Res. 2019;175:8–12. DOI: 10.1016/j.thromres.2019.01.007.
  10. Lisman T., Porte R. J. Towards a rational use of low-molecularweight heparin in patients with cirrhosis. Liver Int. 2011;31(7):1063. DOI: 10.1111/j.14783231.2011.02489.x.
  11. Potze W., Arshad F., Adelmeijer J., et al. Routine coagulation assays underestimate levels of antithrombin-dependent drugs but not of direct anticoagulant drugs in plasma from patients with cirrhosis. Br J Haematol. 2013;163(5):666–73. DOI: 10.1111/bjh.12593.
  12. White H., Sosnowski K., Bird R. et al. The utility of thromboelas-tography in monitoring low molecular weight heparin therapy in the coronary care unit. Blood Coagul Fibrinolysis. 2012;23(4):304– 10. DOI: 10.1097/MBC.0b013e32835274c0.
  13. Poletaev A. V., Balandina A. N., Rabotinskiy S. E. et al. The use of global hemostasis assays to monitor the effectiveness of low molecular weight heparins. Vestnik poslediplomnogo medicinskogo obrazovaniya. 2013;(3):45. (In Russ.).
  14. Tekkesin N., Tekkesin M., Kaso G. Thromboelastography for the monitoring of the antithrombotic effect of low-molecular weight heparin after major orthopedic surgery. Anatol J Cardiol. 2015;15(11):932–7. DOI: 10.5152/akd.2014.5723.
  15. Chow L., Carr A., MacKenzie L. et al. The effect of dalteparin on thromboelastography in pregnancy: an in vitro study. Int J Obstet Anesth. 2016;28:22–7. DOI: 10.1016/j.ijoa.2016.08.002.
  16. Feuring M., Wehling M., Schultz A. Dalteparin dose-dependently increases ROTEM(®) thrombelastography parameters only at supratherapeutic anti-factor Xa levels: an in vitro study. Clin Exp Pharma col Physiol. 2011;38(11):783–6. DOI: 10.1111/j.14401681.2011.05593.x.
  17. Harenberg J. Thrombelastometer and low molecular weight he parin. Anaesthesia. 2009;64(8):920–1. DOI: 10.1111/j.13652044. 2009.06025.x.
  18. Yudin D. V., Shulutko E. M., Valetova V. V. et al. The choice among thromboelastometry tests to assess effects of low molecular weight heparins administered in prevention doses. Tromboz, gemostaz i reologiya. 2020;(4):71–7. (In Russ.). DOI: 10.25555/THR.2020.4.0948.
  19. Georgiadou P., Sokou R., Tsantes A. G. et al. The non-activated thromboelastometry (NATEM) assay’s application among adults and neonatal/pediatric population: a systematic review. Diagnostics (Basel). 2022;12(3):658. DOI: 10.3390/diagnostics12030658.
  20. Bozhkova S. A., Bulanov A.Yu., Vavilova T. V. et al. National stan dard of the Russian Federation GOST R 56377–2015. Clinical re commendations (Protocols for patient’s cure). Prevention of thromboembolic syndromes. Problemy standartizacii v zdra voohranenii. 2015;(7–8):28–68. (In Russ.).
  21. Bulanov A.Yu., Prasolov N. V., Yatskov K. V. Thromboelastography in the practice of anesthesia and intensive care in obstetrics. Clinical recommendations. Treatment protocols. Rossijskij universitet druzhby narodov. Gorodskaya klinicheskaya bol’nica № 52 DZM. 2014;52:460–8. (In Russ.). Available at: https://www.arfpoint. ru/wpcontent/uploads/2014/06/24_Glava_24.pdf. [Accessed: 20.01.2024].
  22. Bulanov A.Yu., Gatsolaeva D. S., Bulanov E. L., Dobrova N. V. TEG control of oral anticoagulants — direct inhibitors. Tromboz, gemostaz i reologiya. 2016;(S3):82–3. (In Russ.).
  23. Connelly C. R., Van P. Y., Hart K. D. et al. Thrombelastographybased dosing of enoxaparin for thromboprophylaxis in trauma and surgical patients: a randomized clinical trial. JAMA Surg. 2016;151(10): e162069. DOI: 10.1001/jamasurg.2016.2069.
  24. Artang R., Frandsen N. J., Nielsen J. D. Application of basic and composite thrombelastography parameters in monitoring of the antithrombotic effect of the low molecular weight heparin dalteparin: an in vivo study. Thromb J. 2009;7:14. DOI: 10.1186/14779560714.