Correlation between different anticoagulation monitoring indicators and concentration of unfractionated heparin during extracorporeal membrane oxygenation in children after cardiac surgery_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

SHEN Ruihuan ,  WANG Xu , LU Zhongyuan , JIANG Yazhou

Department of Pediatric Cardiac Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, P. R. China;

Corresponding author：

WANG Xu, Email: fwpicu@163.com

Keywords：

Activated partial thromboplastin time; activated clotting time; anti-Xa activity; extracorporeal membrane oxygenation; unfractionated heparin

DOI：

10.7507/1007-4848.202102011

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To evaluate the correlation of activated partial thromboplastin time (aPTT), activated clotting time (ACT) and the activity of anti-factor Ⅹa activity with the concentration of unfractionated heparin (UFH) during extracorporeal membrane oxygenation (ECMO) in children after cardiac surgery.Methods The clinical data of children (aged 6 months to 6 years) who received ECMO support after cardiac surgery in Fuwai Hospital from January 2010 to October 2020 were retrospectively collected. And the aPTT value, ACT value, anti-Ⅹa activity and the corresponding UFH dose measured simultaneously during ECMO were recorded. According to the Extracorporeal Life Support Organization anticoagulation guideline, the bleeding events of children during ECMO support were defined, and the children were divided into a bleeding group and a non-bleeding group according to whether bleeding events occurred. Pearson correlation was used to evaluate the correlation between ACT, aPTT or anti-Ⅹa activity and UFH in the same patient.Results A total of 58 children, including 33 males and 25 females, aged 27.31±34.17 months, were enrolled and divided into the bleeding group (n=39) and the non-bleeding group (n=19). Univariate analysis showed that compared with children in the non-bleeding group, children in the bleeding group had lower red blood cell counts (P=0.049), hemoglobin concentration (P=0.010), and hematocrit (P=0.046) on the day of ECMO installation. In addition, the transfusion volume of fresh frozen plasma (P=0.034) and fibrinogen (P=0.033) in the bleeding group was relatively more, and the proportion of exploratory thoracotomy for hemostasis was high (P=0.000); there was a moderate degree of correlation between anti-Ⅹa and UFH (r=0.418, P=0.013) but there was no correlation between ACT or aPTT and UFH.Conclusion The aPTT value and ACT value are poorly correlated with the concentration of UFH transfused during ECMO in children after cardiac surgery, while the anti-Ⅹa activity is moderately correlated with it.

1.	Karagiannidis C, Brodie D, Strassmann S, et al. Extracorporeal membrane oxygenation: Evolving epidemiology and mortality. Intensive Care Med, 2016, 42(5): 889-896.
2.	Sauer CM, Yuh DD, Bonde P. Extracorporeal membrane oxygenation use has increased by 433% in adults in the United States from 2006 to 2011. ASAIO J, 2015, 61(1): 31-36.
3.	Chen Z, Mondal NK, Zheng S, et al. High shear induces platelet dysfunction leading to enhanced thrombotic propensity and diminished hemostatic capacity. Platelets, 2019, 30(1): 112-119.
4.	Chen Z, Mondal NK, Ding J, et al. Paradoxical effect of nonphysiological shear stress on platelets and von willebrand factor. Artif Organs, 2016, 40(7): 659-668.
5.	Oliver WC. Anticoagulation and coagulation management for ECMO. Semin Cardiothorac Vasc Anesth, 2009, 13(3): 154-175.
6.	Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the full-term infant. Blood, 1987, 70(1): 165-172.
7.	Andrew M, Vegh P, Johnston M, et al. Maturation of the hemostatic system during childhood. Blood, 1992, 80(8): 1998-2005.
8.	Toulon P, Berruyer M, Brionne-François M, et al. Age dependency for coagulation parameters in paediatric populations. Results of a multicentre study aimed at defining the age-specific reference ranges. Thromb Haemost, 2016, 116(1): 9-16.
9.	Favaloro EJ, Lippi G. Translational aspects of developmental hemostasis: Infants and children are not miniature adults and even adults may be different. Ann Transl Med, 2017, 5(10): 212.
10.	Reed RC, Rutledge JC. Laboratory and clinical predictors of thrombosis and hemorrhage in 29 pediatric extracorporeal membrane oxygenation nonsurvivors. Pediatr Dev Pathol, 2010, 13(5): 385-392.
11.	Young E, Prins M, Levine MN, et al. Heparin binding to plasma proteins, an important mechanism for heparin resistance. Thromb Haemost, 1992, 67(6): 639-643.
12.	Vieira A, Berry L, Ofosu F, et al. Heparin sensitivity and resistance in the neonate: An explanation. Thromb Res, 1991, 63(1): 85-98.
13.	Bembea MM, Annich G, Rycus P, et al. Variability in anticoagulation management of patients on extracorporeal membrane oxygenation: an international survey. Pediatr Crit Care Med, 2013, 14(2): e77-84.
14.	Esper SA, Welsby IJ, Subramaniam K, et al. Adult extracorporeal membrane oxygenation: An international survey of transfusion and anticoagulation techniques. Vox Sang, 2017, 112(5): 443-452.
15.	Lequier L, Massicotte MP. Monitoring of anticoagulation in extracorporeal membrane oxygenation: Is anti-Ⅹa the new activated clotting time? Pediatr Crit Care Med, 2015, 16(1): 87-89.
16.	Vera-Aguilera J, Yousef H, Beltran-Melgarejo D, et al. Clinical scenarios for discordant Anti-Ⅹa. Adv Hematol, 2016, 2016: 4054806.
17.	Lequier L, Annich G, Al-Ibrahim O, et al. Extracorporeal Life Support Organization (ELSO) anticoagulation guideline, 2014. (2018-8-1) https://www.elso.org/portals/0/files/elsoanticoagulationguideline8-2014-table-contents.pdf.
18.	Odegard KC, McGowan FX Jr, Zurakowski D, et al. Procoagulant and anticoagulant factor abnormalities following the Fontan procedure: increased factor VⅢ may predispose to thrombosis. J Thorac Cardiovasc Surg, 2003, 125(6): 1260-1267.
19.	Odegard KC, Zurakowski D, Hornykewycz S, et al. Evaluation of the coagulation system in children with two-ventricle congenital heart disease. Ann Thorac Surg, 2007, 83(5): 1797-1803.
20.	Esper SA, Levy JH, Waters JH, et al. Extracorporeal membrane oxygenation in the adult: A review of anticoagulation monitoring and transfusion. Anesth Analg, 2014, 118(4): 731-743.
21.	Kuhle S, Eulmesekian P, Kavanagh B, et al. Lack of correlation between heparin dose and standard clinical monitoring tests in treatment with unfractionated heparin in critically ill children. Haematologica, 2007, 92(4): 554-557.
22.	Despotis GJ, Summerfield AL, Joist JH, et al. Comparison of activated coagulation time and whole blood heparin measurements with laboratory plasma anti-Ⅹa heparin concentration in patients having cardiac operations. J Thorac Cardiovasc Surg, 1994, 108(6): 1076-1082.
23.	Chan AK, Leaker M, Burrows FA, et al. Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. Thromb Haemost, 1997, 77(2): 270-277.
24.	Owings JT, Pollock ME, Gosselin RC, et al. Anticoagulation of children undergoing cardiopulmonary bypass is overestimated by current monitoring techniques. Arch Surg, 2000, 135(9): 1042-1047.
25.	Nankervis CA, Preston TJ, Dysart KC, et al. Assessing heparin dosing in neonates on venoarterial extracorporeal membrane oxygenation. ASAIO J, 2007, 53(1): 111-114.
26.	Khaja WA, Bilen O, Lukner RB, et al. Evaluation of heparin assay for coagulation management in newborns undergoing ECMO. Am J Clin Pathol, 2010, 134(6): 950-954.
27.	Bembea MM, Schwartz JM, Shah N, et al. Anticoagulation monitoring during pediatric extracorporeal membrane oxygenation. ASAIO J, 2013, 59(1): 63-68.
28.	Williams MD, Chalmers EA, Gibson BE. Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology. The investigation and management of neonatal haemostasis and thrombosis. Br J Haematol, 2002, 119(2): 295-309.
29.	Silva RCLS, Grabowski EF. Flow devices to assess platelet function: Historical evolution and current choices. Semin Thromb Hemost, 2019, 45(3): 297-301.
30.	Six KR, Devloo R, Van Aelst B, Vandekerckhove P, et al. Compernolle Ⅴ. A microfluidic flow chamber model for platelet transfusion and hemostasis measures platelet deposition and fibrin formation in real-time. J Vis Exp, 2017, (120): 55351.

1. Karagiannidis C, Brodie D, Strassmann S, et al. Extracorporeal membrane oxygenation: Evolving epidemiology and mortality. Intensive Care Med, 2016, 42(5): 889-896.
2. Sauer CM, Yuh DD, Bonde P. Extracorporeal membrane oxygenation use has increased by 433% in adults in the United States from 2006 to 2011. ASAIO J, 2015, 61(1): 31-36.
3. Chen Z, Mondal NK, Zheng S, et al. High shear induces platelet dysfunction leading to enhanced thrombotic propensity and diminished hemostatic capacity. Platelets, 2019, 30(1): 112-119.
4. Chen Z, Mondal NK, Ding J, et al. Paradoxical effect of nonphysiological shear stress on platelets and von willebrand factor. Artif Organs, 2016, 40(7): 659-668.
5. Oliver WC. Anticoagulation and coagulation management for ECMO. Semin Cardiothorac Vasc Anesth, 2009, 13(3): 154-175.
6. Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the full-term infant. Blood, 1987, 70(1): 165-172.
7. Andrew M, Vegh P, Johnston M, et al. Maturation of the hemostatic system during childhood. Blood, 1992, 80(8): 1998-2005.
8. Toulon P, Berruyer M, Brionne-François M, et al. Age dependency for coagulation parameters in paediatric populations. Results of a multicentre study aimed at defining the age-specific reference ranges. Thromb Haemost, 2016, 116(1): 9-16.
9. Favaloro EJ, Lippi G. Translational aspects of developmental hemostasis: Infants and children are not miniature adults and even adults may be different. Ann Transl Med, 2017, 5(10): 212.
10. Reed RC, Rutledge JC. Laboratory and clinical predictors of thrombosis and hemorrhage in 29 pediatric extracorporeal membrane oxygenation nonsurvivors. Pediatr Dev Pathol, 2010, 13(5): 385-392.
11. Young E, Prins M, Levine MN, et al. Heparin binding to plasma proteins, an important mechanism for heparin resistance. Thromb Haemost, 1992, 67(6): 639-643.
12. Vieira A, Berry L, Ofosu F, et al. Heparin sensitivity and resistance in the neonate: An explanation. Thromb Res, 1991, 63(1): 85-98.
13. Bembea MM, Annich G, Rycus P, et al. Variability in anticoagulation management of patients on extracorporeal membrane oxygenation: an international survey. Pediatr Crit Care Med, 2013, 14(2): e77-84.
14. Esper SA, Welsby IJ, Subramaniam K, et al. Adult extracorporeal membrane oxygenation: An international survey of transfusion and anticoagulation techniques. Vox Sang, 2017, 112(5): 443-452.
15. Lequier L, Massicotte MP. Monitoring of anticoagulation in extracorporeal membrane oxygenation: Is anti-Ⅹa the new activated clotting time? Pediatr Crit Care Med, 2015, 16(1): 87-89.
16. Vera-Aguilera J, Yousef H, Beltran-Melgarejo D, et al. Clinical scenarios for discordant Anti-Ⅹa. Adv Hematol, 2016, 2016: 4054806.
17. Lequier L, Annich G, Al-Ibrahim O, et al. Extracorporeal Life Support Organization (ELSO) anticoagulation guideline, 2014. (2018-8-1) https://www.elso.org/portals/0/files/elsoanticoagulationguideline8-2014-table-contents.pdf.
18. Odegard KC, McGowan FX Jr, Zurakowski D, et al. Procoagulant and anticoagulant factor abnormalities following the Fontan procedure: increased factor VⅢ may predispose to thrombosis. J Thorac Cardiovasc Surg, 2003, 125(6): 1260-1267.
19. Odegard KC, Zurakowski D, Hornykewycz S, et al. Evaluation of the coagulation system in children with two-ventricle congenital heart disease. Ann Thorac Surg, 2007, 83(5): 1797-1803.
20. Esper SA, Levy JH, Waters JH, et al. Extracorporeal membrane oxygenation in the adult: A review of anticoagulation monitoring and transfusion. Anesth Analg, 2014, 118(4): 731-743.
21. Kuhle S, Eulmesekian P, Kavanagh B, et al. Lack of correlation between heparin dose and standard clinical monitoring tests in treatment with unfractionated heparin in critically ill children. Haematologica, 2007, 92(4): 554-557.
22. Despotis GJ, Summerfield AL, Joist JH, et al. Comparison of activated coagulation time and whole blood heparin measurements with laboratory plasma anti-Ⅹa heparin concentration in patients having cardiac operations. J Thorac Cardiovasc Surg, 1994, 108(6): 1076-1082.
23. Chan AK, Leaker M, Burrows FA, et al. Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. Thromb Haemost, 1997, 77(2): 270-277.
24. Owings JT, Pollock ME, Gosselin RC, et al. Anticoagulation of children undergoing cardiopulmonary bypass is overestimated by current monitoring techniques. Arch Surg, 2000, 135(9): 1042-1047.
25. Nankervis CA, Preston TJ, Dysart KC, et al. Assessing heparin dosing in neonates on venoarterial extracorporeal membrane oxygenation. ASAIO J, 2007, 53(1): 111-114.
26. Khaja WA, Bilen O, Lukner RB, et al. Evaluation of heparin assay for coagulation management in newborns undergoing ECMO. Am J Clin Pathol, 2010, 134(6): 950-954.
27. Bembea MM, Schwartz JM, Shah N, et al. Anticoagulation monitoring during pediatric extracorporeal membrane oxygenation. ASAIO J, 2013, 59(1): 63-68.
28. Williams MD, Chalmers EA, Gibson BE. Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology. The investigation and management of neonatal haemostasis and thrombosis. Br J Haematol, 2002, 119(2): 295-309.
29. Silva RCLS, Grabowski EF. Flow devices to assess platelet function: Historical evolution and current choices. Semin Thromb Hemost, 2019, 45(3): 297-301.
30. Six KR, Devloo R, Van Aelst B, Vandekerckhove P, et al. Compernolle Ⅴ. A microfluidic flow chamber model for platelet transfusion and hemostasis measures platelet deposition and fibrin formation in real-time. J Vis Exp, 2017, (120): 55351.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesCorrelation between different anticoagulation monitoring indicators and concentration of unfractionated heparin during extracorporeal membrane oxygenation in children after cardiac surgery

Abstract Full text Figures/Tables Video References Cited by

Format

Content