Clinical Physiology of Circulation

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


Evaluation of the natural anticoagulants activity in diagnostic algorithms in cardiac surgery patients

Authors: Rogal’skaya E.A., Rybka M.M., Meshchanov B.V., Esayan G.S., Mumladze K.V., Samsonova N.N.

Company:
Bakoulev National Medical Research Center for Cardiovascular Surgery, Moscow, Russian Federation

E-mail: Сведения доступны для зарегистрированных пользователей.

DOI: https://doi.org/10.24022/1814-6910-2021-18-3-231-240

UDC: 615.273.53:615.38:616.12-089.5-06

Link: Clinical Physiology of Blood Circulaiton. 2021; 3 (18): 231-240

Quote as: Rogal’skaya E.A., Rybka M.M., Meshchanov B.V., Esayan G.S., Mumladze K.V., Samsonova N.N. Evaluation of the natural anticoagulants activity in diagnostic algorithms in cardiac surgery patients. Clinical Physiology of Circulation. 2021; 18 (3): 231–40 (in Russ.). DOI: 10.24022/1814-6910-2021-18-3-231-240

Received / Accepted:  30.03.2021 / 17.06.2021

Full text:
Subscribe 🔒

Abstract

Objective. To study the dynamics of the activity of natural anticoagulants depending on the variant of cardiac pathology in order to search for criteria for inclusion of patients in a cohort with an increased risk of developing intra- and postoperative thrombosis.

Material and methods. The study included 92 patients with a median age of 61 years (range 55; 66) with surgical correction of valvular heart disease, ischemic heart disease (IHD), or their combination under cardiopulmonary bypass. Research stages: before a skin incision, after suturing a surgical wound, 24 hours after the start of an operation; in patients with combined pathology, additionally – after a single dose of warfarin.

Results. All patients have a reduced preoperative antithrombin level, which is further reduced during surgical correction. In patients with pathology of the mitral valve (MVP), both isolated and in combination with IHD, an initially decreased protein C (PC) activity is observed. In accordance with the dynamics of the level of natural anticoagulants, the leading cause of the observed changes is a mitral valve disease. When MVP is combined with IHD, the most pronounced changes are observed: the maximum decrease of PC activity during an operation and not complete recovery by the end of the first operating day. After an administration of warfarin to patients of this study group, the dynamics of recovery is interrupted and the PC decreases again. At the same time, the activity of protein C and S does not reach critically low thrombogenic values.

Conclusion. Patients with a combination of MVP and ischemic heart disease need in a monitoring of an activity of natural anticoagulants to rationalize anticoagulant therapy. Taking into account the lack of results of critically low values of proteins C and S, as well as from the point of view of economic feasibility, to prevent a thrombosis of thin intervascular anastomoses in patients with a combination of MVP and IHD, it is important to include the study of antithrombin activity before surgery, intraoperatively and during the first postoperative days in the algorithm of clinical and laboratory assessment of the state of the hemostasis system.

References

  1. Бокерия Л.А. (ред.). Сердечно-сосудистая хирургия – 2019. М.: НМИЦ ССХ им. А.Н. Бакулева МЗ РФ; 2020.
  2. Рыбка М.М., Рогальская Е.А., Мещанов Б.В., Самсонова Н.Н., Климович Л.Г., Хинчагов Д.Я. и др. Оценка уровня естественных антикоагулянтов у пациентов с ИБС в сочетании с патологией митрального клапана в периоперационном периоде. Анестезиология и реаниматология. 2017; 62 (5): 342–6. DOI: 10.18821/0201-7563-2017-62-5-342-346
  3. Рыбка М.М., Рогальская Е.А., Мещанов Б.В., Самсонова Н.Н., Климович Л.Г., Хинчагов Д.Я. и др. Периоперационная динамика активности антитромбина у пациентов с ишемической болезнью сердца в сочетании с патологией митрального клапана. Клиническая физиология кровообращения. 2017; 14 (2): 91–5. DOI: 10.24022/1814-6910-2017-14-2-91-95
  4. Самсонова Н.Н., Климович Л.Г. Интерактивные проблемы кардиологии: современные представления о системе гемостаза. В кн.: Бокерия Л.А., Голухова Е.З. (ред.). Клиническая кардиология: диагностика и лечение. Т. 3. М.: НЦССХ им. А.Н. Бакулева РАМН; 2011.
  5. Maclean P.S., Tait R.C. Hereditary and acquired antithrombin deficiency. Drugs. 2007; 67: 1429–40. DOI: 10.2165/00003495-200767100-00005
  6. Brown M.E., Gallagher J.M., Armitage J.M. The use of human antithrombin III concentrate for treatment of heparin resistance during cardiopulmonary bypass. J. Extra-corp. Technol. 2000; 32 (2): 75–8.
  7. Рыбка М.М., Рогальская Е.А., Мещанов Б.В., Лагутина О.В., Мумладзе К.В. Коррекция дефицита антитромбина в периоперационном периоде у кардиохирургических пациентов. Тромбоз, гемостаз и реология. 2020; 3: 39–46. DOI: 10.25555/THR. 2020.3.0927
  8. Ланг Т.А., Сесик М. (ред.). Как описывать статистику в медицине. Аннотированное руководство для авторов, редакторов и рецензентов. М.: Практическая медицина; 2011.
  9. Sniecinski R., Szlam F., Chen E.P., Bader S.O., Stephen O. et al. Antithrombin deficiency increases thrombin activity after prolonged cardiopulmonary bypass. Anesth. Analg. 2008; 106 (3): 713–8. DOI: 10.1213/ane. 0b013e3181608f7c
  10. Sokol J., Timp J.F., Le Cessie S., van Hylckama-Vlieg А., Rosendaal F.R., Kubisz P. et al. Mild antithrombin deficiency and risk of recurrent venous thromboembolism: results from the MEGA follow-up study. J. Thromb. Haemost. 2018; 16: 680–8. DOI: 10.1111/jth.13960
  11. Галстян Г.М., Денисова Е.Н., Куприкова А.И., Орел Е.Б., Бирюкова Л.С. Применение препарата антитромбина III для системной антикоагуляции при проведении процедур с использованием экстракорпорального контура. Вестник анестезиологии и реаниматологии. 2013; 10 (5): 36–46.
  12. Ryerson L.M., Lequier L.L. Anticoagulation management and monitoring during pediatric extracorporeal life support: a review of current issues. Front Pediatr. 2016; 4: 67. DOI: 10.3389/fped.2016.00067
  13. Ranucci M., Baryshnikova E., Crapelli G.B., Woodward M.K., Paez A., Pelissero G. et al. Preoperative antithrombin supplementation in cardiac surgery: a randomized controlled trial. J. Thorac. Cardiovasc. Surg. 2013; 145 (5): 1393–9. DOI: 10.1016/j.jtcvs.2012. 09.061
  14. Raphael J., Mazer C.D., Wilkey A., Subramani S., Schroeder A., Abdalla M. et al. Corrigendum to 'Society of Cardiovascular Anesthesiologists (SCA) Clinical Practice Improvement (CPI) Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients'. J. Cardiothorac. Vasc. Anesth. 2019; 33: 2887–99. DOI: 10.1053/j.jvca.2019. 11.004
  15. Селюн Ю.А., Валентюкевич А.В., Колядко М.Г., Островский Ю.П. Дефицит активности антитромбина III и его коррекция у кардиохирургического пациента. Медицинские новости. 2018; 4 (283): 46–50.
  16. Garvin S., Muehlschlegel J.D., Perry T.E., Chen J., Liu К.Y., Fox A.A. et al. Postoperative activity, but not preoperative activity, of antithrombin is associated with major adverse cardiac events after coronary artery bypass graft surgery. Anesth. Analg. 2010; 111 (4): 862–9. DOI: 10.1213/ANE.0b013e3181b7908c
  17. Paparella D., Cappabianca G., Scrascia G., Fiore G., Paramythiotis A., Di Bari N. et al. Antithrombin after cardiac surgery: implications on short and mid-term outcome. J. Thromb. Thrombolysis. 2009; 27 (1): 105–14. DOI: 10.1007/s11239-007-0191-9
  18. Dinarvand P., Moser K.A. Protein C Deficiency. Arch. Pathol. Lab. Med. 2019; 143 (10): 1281–5. DOI: 10.5858/arpa.2017-0403-RS
  19. Moster M.L. Coagulopathies and arterial stroke. J. Neuroophthalmol. 2003; 23 (1): 63–71. DOI: 10.1097/ 00041327-200303000-00012
  20. Walenga J.M., Torres T.A., Jeske W.P., Schwartz J., Escalante V., Newman J.D., Bakhos M. Protein C pathway, inflammation, and pump thrombosis in patients with left ventricular assist devices. Clin. Appl. Thromb. Hemost. 2020. DOI: 10.1177/ 1076029620959724
  21. Oshima Y., Yamasaki K., Otsuki A., Nakasone M., Endo R., Moriyama N. et al. Peripartum myocardial infarction associated with coronary spasm and acquired protein S deficiency: a case report. Medicine Анестезиология и реанимация 239 Клиническая физиология кровообращения. 2021; 18 (3). DOI: 10.24022/1814-6910-2021-18-3-231-240 (Baltimore). 2019; 98 (48): e18108. DOI: 10.1097/MD.0000000000018108
  22. Massoudy P., Thielmann M., Müller-Beissenhirtz H., Aleksic I., Marggraf G., Dietrich W., Jakob H. Thrombophilia in cardiac surgery – patients with protein S deficiency. Ann. Thorac. Surg. 2006; 82 (6): 2187–91. DOI: 10.1016/j.athoracsur.2006.06.066
  23. Прасолов Н.В., Шулутко Е.М., Буланов А.Ю., Яцков К.В., Щербакова О.В. Экстренная терапия кровотечений у пациентов, принимающих варфарин. Анестезиология и реаниматология. 2015; 60 (2): 72–6.
  24. Pourdeyhimi N., Bullard Z. Warfarin-induced skin necrosis. Hosp. Pharm. 2014; 49 (11): 1044–8. DOI: 10.1310/ hjp4911-1044 26. Akbayrak H. Warfarin-induced skin necrosis after coronary artery bypass grafting. Tex. Heart Inst. J. 2020; 47 (4): 333–4. DOI: 10.14503/THIJ-18-6616
  25. Инструкция по медицинскому применению препарата Варфарин Канон. Регистрационный номер: LSR-006276/09. http://www.canonpharma.ru/ru/drugs/cardiology/varfarin (дата обращения 20.02.2021).
  26. Binymin K.A., Nasher M., Patel D. Warfarin-induced deep vein thrombosis. Int. Med. Case Rep. J. 2014; 7: 123–5. DOI: 10.2147/IMCRJ.S62100
  27. Minford A., Behnisch W., Brons P., David M., Gomez Gomez N., Hertfelder H.J. et al. Subcutaneous protein C concentrate in the management of severe protein C deficiency – experience from 12 centres. Br. J. Haematol. 2014; 164 (3): 414–21. DOI: 10.1111/ bjh.12640
  28. De Kort E.H.M., Vrancken S.L.A.G., van Heijst A.F.J., Binkhorst M., Cuppen M.P.J.M., Brons P.P.T. et al. Longterm subcutaneous protein C replacement in neonatal severe protein C deficiency. Pediatrics. 2011; 127: e1338–42. DOI: 10.1542/peds2009-2913
****
  1. Bockeria L.A. (Ed.). Cardiovascular surgery – 2019. Moscow; 2020 (in Russ.).
  2. Rybka M.M., Rogalskaya E.A., Meshchanov B.V., Samsonova N.N., Klimovich L.G., Khinchagov D.Ya. et al. Assessment of the natural anticoagulants level in patients with coronary heart disease with pathology of the mitral valve in the perioperative period. Russian Journal of Аnaesthesiology and Reanimatology. 2017; 62 (5): 342–6 (in Russ.). DOI: 10.18821/0201-7563-2017-62-5-342-346
  3. Rybka M.M., Rogal’skaya E.A., Meshchanov B.V., Samsonova N.N., Klimovich L.G., Khinchagov D.Ya. et al. Perioperative antithrombin activity in patients with coronary heart disease combined with pathology of the mitral valve. Сlinical Physiology of Сirculation. 2017; 14 (2): 91–5 (in Russ.). DOI: 10.24022/1814-6910- 2017-14-2-91-95
  4. Samsonova N.N., Klimovich L.G. Interactive problems of cardiology: modern concepts of the hemostasis system. In: Bockeria L.A., Golukhova E.Z. (Eds.) Clinical cardiology: diagnosis and treatment. Vol. 3. Moscow; 2011 (in Russ.).
  5. Nishimura Y., Takagi Y. Strategy for cardiovascular surgery in patients with antithrombin III deficiency. Ann. Thorac. Cardiovasc. Surg. 2018; 24 (4): 187–92. DOI: 10.5761/atcs.oa.18-00030
  6. Maclean P.S., Tait R.C. Hereditary and acquired antithrombin deficiency. Drugs. 2007; 67: 1429–40. DOI: 10.2165/00003495-200767100-00005
  7. Brown M.E., Gallagher J.M., Armitage J.M. The use of human antithrombin III concentrate for treatment of heparin resistance during cardiopulmonary bypass. J. Extra-corp. Technol. 2000; 32 (2): 75–8.
  8. Rybka M.M., Rogalskaya E.A., Meshchanov B.V., Lagutina O.V., Mumladze K.V. Correction of antithrombin deficiency in perioperative period in cardiac surgery patients. Thrombosis, Hemostasis and Rheology. 2020; 3: 39–46 (in Russ.). DOI: 10.25555/THR.2020.3.0927
  9. Lang T.A., Sesik M. (Eds). How to report statistics in medicine. Annotated Guidelines for authors, editors, and reviewers. Moscow; 2011 (in Russ.).
  10. Sniecinski R., Szlam F., Chen E.P., Bader S.O., Stephen O. et al. Antithrombin deficiency increases thrombin activity after prolonged cardiopulmonary bypass. Anesth. Analg. 2008; 106 (3): 713–8. DOI: 10.1213/ane. 0b013e3181608f7c
  11. Sokol J., Timp J.F., Le Cessie S., van Hylckama-Vlieg А., Rosendaal F.R., Kubisz P. et al. Mild antithrombin deficiency and risk of recurrent venous thromboembolism: results from the MEGA follow-up study. J. Thromb. Haemost. 2018; 16: 680–8. DOI: 10.1111/jth.13960
  12. Galstyan G.M., Denisova E.N., Kuprikova A.I., Orel E.B., Biryukova L.S. Use of an antithrombim III preparation for systemic anticoagulation during procedures using an extracorporeal circuit. Messenger of Anesthesiology and Resuscitation. 2013; 10 (5): 36–46 (in Russ.).
  13. Ryerson L.M., Lequier L.L. Anticoagulation management and monitoring during pediatric extracorporeal life support: a review of current issues. Front Pediatr. 2016; 4: 67. DOI: 10.3389/fped.2016.00067
  14. Ranucci M., Baryshnikova E., Crapelli G.B., Woodward M.K., Paez A., Pelissero G. et al. Preoperative antithrombin supplementation in cardiac surgery: a randomized controlled trial. J. Thorac. Cardiovasc. Surg. 2013; 145 (5): 1393–9. DOI: 10.1016/j.jtcvs.2012. 09.061
  15. Raphael J., Mazer C.D., Wilkey A., Subramani S., Schroeder A., Abdalla M. et al. Corrigendum to 'Society of Cardiovascular Anesthesiologists (SCA) Clinical Practice Improvement (CPI) Advisory for Management of Perioperative Bleeding and Hemostasis in Cardiac Surgery Patients'. J. Cardiothorac. Vasc. Anesth. 2019; 33: 2887–99. DOI: 10.1053/j.jvca.2019. 11.004
  16. Seliun Yu.A., Valentsiukevich A.V., Kolyadko M.G., Ostrovsky Yu.P. Deficiency of antithrombin III activity and its correction in a cardiosurgical patient. Medicinskie Novosti. 2018; 4 (283): 46–50 (in Russ.).
  17. Garvin S., Muehlschlegel J.D., Perry T.E., Chen J., Liu К.Y., Fox A.A. et al. Postoperative activity, but not preoperative activity, of antithrombin is associated with major adverse cardiac events after coronary artery bypass graft surgery. Anesth. Analg. 2010; 111 (4): 862–9. DOI: 10.1213/ANE.0b013e3181b7908c
  18. Paparella D., Cappabianca G., Scrascia G., Fiore G., Paramythiotis A., Di Bari N. et al. Antithrombin after cardiac surgery: implications on short and mid-term outcome. J. Thromb. Thrombolysis. 2009; 27 (1): 105–14. DOI: 10.1007/s11239-007-0191-9
  19. Dinarvand P., Moser K.A. Protein C Deficiency. Arch. Pathol. Lab. Med. 2019; 143 (10): 1281–5. DOI: 10.5858/arpa.2017-0403-RS
  20. Moster M.L. Coagulopathies and arterial stroke. J. Neuroophthalmol. 2003; 23 (1): 63–71. DOI: 10.1097/ 00041327-200303000-00012
  21. Walenga J.M., Torres T.A., Jeske W.P., Schwartz J., Escalante V., Newman J.D., Bakhos M. Protein C pathway, inflammation, and pump thrombosis in patients with left ventricular assist devices. Clin. Appl. Thromb. Hemost. 2020. DOI: 10.1177/ 1076029620959724
  22. Oshima Y., Yamasaki K., Otsuki A., Nakasone M., Endo R., Moriyama N. et al. Peripartum myocardial infarction associated with coronary spasm and acquired protein S deficiency: a case report. Medicine (Baltimore). 2019; 98 (48): e18108. DOI: 10.1097/MD.0000000000018108
  23. Massoudy P., Thielmann M., Müller-Beissenhirtz H., Aleksic I., Marggraf G., Dietrich W., Jakob H. Thrombophilia in cardiac surgery – patients with protein S deficiency. Ann. Thorac. Surg. 2006; 82 (6): 2187–91. DOI: 10.1016/j.athoracsur.2006.06.066
  24. Prasolov N.V., Shulutko E.M., Bulanov A.Yu., Yatskov K.V., Shcherbakova O.V. Emergency bleeding therapy in patients taking warfarin. Russian Journal of Anaesthesiology and Reanimatology. 2015; 60 (2): 72–6 (in Russ.).
  25. Pourdeyhimi N., Bullard Z. Warfarin-induced skin necrosis. Hosp. Pharm. 2014; 49 (11): 1044–8. DOI: 10.1310/ hjp4911-1044 26. Akbayrak H. Warfarin-induced skin necrosis after coronary artery bypass grafting. Tex. Heart Inst. J. 2020; 47 (4): 333–4. DOI: 10.14503/THIJ-18-6616
  26. Instructions for the medical use of the drug Warfarin. Registration number: LSR-006276/09 (in Russ.). Available at: http://www.canonpharma.ru/ru/drugs/cardiology/varfarin (20.02.2021).
  27. Binymin K.A., Nasher M., Patel D. Warfarin-induced deep vein thrombosis. Int. Med. Case Rep. J. 2014; 7: 123–5. DOI: 10.2147/IMCRJ.S62100
  28. Minford A., Behnisch W., Brons P., David M., Gomez Gomez N., Hertfelder H.J. et al. Subcutaneous protein C concentrate in the management of severe protein C deficiency – experience from 12 centres. Br. J. Haematol. 2014; 164 (3): 414–21. DOI: 10.1111/ bjh.12640
  29. De Kort E.H.M., Vrancken S.L.A.G., van Heijst A.F.J., Binkhorst M., Cuppen M.P.J.M., Brons P.P.T. et al. Longterm subcutaneous protein C replacement in neonatal severe protein C deficiency. Pediatrics. 2011; 127: e1338–42. DOI: 10.1542/peds2009-2913

About Authors

  • Ekaterina A. Rogal’skaya, Cand. Med. Sci., Head of Hematology Laboratory; ORCID
  • Mikhail M. Rybka, Dr. Med. Sci., Head of Department of Anesthesiology, Deputy Director of Bourakovsky Institute of Cardiac Surgery of Bakoulev NMRCCS; ORCID
  • Bair V. Meshchanov, Anesthesiologist-Intensivist; ORCID
  • Galina S. Esayan, Junior Researcher; ORCID
  • Koba V. Mumladze, Anesthesiologist-Intensivist; ORCID
  • Natal’ya N. Samsonova, Dr. Med. Sci., Professor, Chief Researcher; ORCID

 If you found mistakes, select text and press Alt+A