Evaluation of Point-of-Care-Directed Coagulation Management in Pediatric Cardiac Surgery

Abstract

Background Coagulatory alterations are common after pediatric cardiac surgery and can be addressed with point-of-care (POC) coagulation analysis. The aim of the present study is to evaluate a preventive POC-controlled coagulation algorithm in pediatric cardiac surgery.

Methods This single-center, retrospective data analysis included patients younger than 18 years who underwent cardiac surgery with cardiopulmonary bypass (CPB) and received a coagulation therapy according to a predefined POC-controlled coagulation algorithm. Patients were divided into two groups (<10 and >10 kg body weight) because of different CPB priming strategies.

Results In total, 173 surgeries with the use of the POC-guided hemostatic therapy were analyzed. In 71% of cases, target parameters were achieved and only in one case primary sternal closure was not possible. Children with a body weight ≤10 kg underwent surgical re-evaluation in 13.2% (15/113), and respectively 6.7% (4/60) in patients >10 kg. Hemorrhage in children ≤10 kg was associated with cyanotic heart defects, deeper intraoperative hypothermia, longer duration of CPB, more complex procedures (RACHS-1 score), and with more intraoperative platelets, and respectively red blood cell concentrate transfusions (all p-values < 0.05). In children ≤10 kg, fibrinogen levels were significantly lower over the 12-hour postoperative period (without revision: 3.1 [2.9–3.3] vs. with revision 2.8 [2.3–3.4]). Hemorrhage in children >10 kg was associated with a longer duration of CPB (p = 0.042), lower preoperative platelets (p = 0.026), and over the 12-hour postoperative period lower platelets (p = 0.002) and fibrinogen (p = 0.05).

Conclusion The use of a preventive, algorithm-based coagulation therapy with factor concentrates after CPB followed by POC created intraoperative clinical stable coagulation status with a subsequent executable thorax closure, although the presented algorithm in its current form is not superior in the reduction of the re-exploration rate compared to equivalent collectives. Reduced fibrinogen concentrations 12 hours after surgery may be associated with an increased incidence of surgical revisions.

Keywords

transfusion - blood - cardiopulmonary bypass - CPB - pediatric - surgery - complications

Publication History

Received: 16 April 2024

Accepted: 19 July 2024

Article published online:
13 August 2024

• References

• 1 Guzzetta NA, Allen NN, Wilson EC, Foster GS, Ehrlich AC, Miller BE. Excessive postoperative bleeding and outcomes in neonates undergoing cardiopulmonary bypass. Anesth Analg 2015; 120 (02) 405-410
• 2 Kipps AK, Wypij D, Thiagarajan RR, Bacha EA, Newburger JW. Blood transfusion is associated with prolonged duration of mechanical ventilation in infants undergoing reparative cardiac surgery. Pediatr Crit Care Med 2011; 12 (01) 52-56
• 3 Wolf MJ, Maher KO, Kanter KR, Kogon BE, Guzzetta NA, Mahle WT. Early postoperative bleeding is independently associated with increased surgical mortality in infants after cardiopulmonary bypass. J Thorac Cardiovasc Surg 2014; 148 (02) 631-6.e1
• 4 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992; 80 (08) 1998-2005
• 5 Höfer J, Fries D, Solomon C, Velik-Salchner C, Ausserer J. A snapshot of coagulopathy after cardiopulmonary bypass. Clin Appl Thromb Hemost 2016; 22 (06) 505-511
• 6 Levy JH, Tanaka KA. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 2003; 75 (02) S715-S720
• 7 Spiezia L, Di Gregorio G, Campello E. et al. Predictors of postoperative bleeding in children undergoing cardiopulmonary bypass: a preliminary Italian study. Thromb Res 2017; 153: 85-89
• 8 Yeh T, Kavarana MN. Cardiopulmonary bypass and the coagulation system. Prog Pediatr Cardiol 2005; 21: 87-115
• 9 Cavalcanti PEF, Sá MP, Santos CA. et al. Stratification of complexity in congenital heart surgery: comparative study of the Risk Adjustment for Congenital Heart Surgery (RACHS-1) method, Aristotle basic score and Society of Thoracic Surgeons-European Association for Cardio- Thoracic Surgery (STS-EACTS) mortality score. Braz J Cardiovasc Surg 2015; 30 (02) 148-158
• 10 Gottlieb EA, Andropoulos DB. Current and future trends in coagulation management for congenital heart surgery. J Thorac Cardiovasc Surg 2017; 153 (06) 1511-1515
• 11 Selby R. “TEG talk”: expanding clinical roles for thromboelastography and rotational thromboelastometry. Hematology (Am Soc Hematol Educ Program) 2020; 2020 (01) 67-75
• 12 Korpallová B, Samoš M, Bolek T. et al. Role of thromboelastography and rotational thromboelastometry in the management of cardiovascular diseases. Clin Appl Thromb Hemost 2018; 24 (08) 1199-1207
• 13 Drotarova M, Zolkova J, Belakova KM. et al. Basic principles of rotational thromboelastometry (ROTEM^®) and the role of ROTEM-guided fibrinogen replacement therapy in the management of coagulopathies. Diagnostics (Basel) 2023; 13 (20) 3219
• 14 Perry DJ. A practical guide to haemostasis. Accessed May 31, 2024 at: Practical-Haemostasis.com
• 15 Naguib AN, Carrillo SA, Corridore M. et al. A ROTEM-guided algorithm aimed to reduce blood product utilization during neonatal and infant cardiac surgery. J Extra Corpor Technol 2023; 55 (02) 60-69
• 16 Nakayama Y, Nakajima Y, Tanaka KA. et al. Thromboelastometry-guided intraoperative haemostatic management reduces bleeding and red cell transfusion after paediatric cardiac surgery. Br J Anaesth 2015; 114 (01) 91-102
• 17 Romlin BS, Wåhlander H, Berggren H. et al. Intraoperative thromboelastometry is associated with reduced transfusion prevalence in pediatric cardiac surgery. Anesth Analg 2011; 112 (01) 30-36
• 18 Sun W, Jeleniowski K, Zhao X, Shen P, Li D, Hammond JA. Thromboelastography (TEG)-based algorithm reduces blood product utilization in patients undergoing VAD implant. J Card Surg 2014; 29 (02) 238-243
• 19 Whitney G, Daves S, Hughes A. et al. Implementation of a transfusion algorithm to reduce blood product utilization in pediatric cardiac surgery. Paediatr Anaesth 2013; 23 (07) 639-646
• 20 Wikkelsø A, Wetterslev J, Møller AM, Afshari A. Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding. Cochrane Database Syst Rev 2016; 2016 (08) CD007871
• 21 Guzzetta NA, Williams GD. Current use of factor concentrates in pediatric cardiac anesthesia. Paediatr Anaesth 2017; 27 (07) 678-687
• 22 Faraoni D, Willems A, Romlin BS, Belisle S, Van der Linden P. Development of a specific algorithm to guide haemostatic therapy in children undergoing cardiac surgery: a single-centre retrospective study. Eur J Anaesthesiol 2015; 32 (05) 320-329
• 23 Machovec KA, Jooste EH. Pediatric transfusion algorithms: coming to a cardiac operating room near you. J Cardiothorac Vasc Anesth 2019; 33 (07) 2017-2029
• 24 Najafi M, Faraoni D. Updates on coagulation management in cardiac surgery. J Tehran Heart Cent 2014; 9 (03) 99-103
• 25 Bianchi P, Beccaris C, Norbert M, Dunlop B, Ranucci M. Use of coagulation point-of-care tests in the management of anticoagulation and bleeding in pediatric cardiac surgery: a systematic review. Anesth Analg 2020; 130 (06) 1594-1604
• 26 Haas T, Spielmann N, Mauch J. et al. Comparison of thromboelastometry (ROTEM®) with standard plasmatic coagulation testing in paediatric surgery. Br J Anaesth 2012; 108 (01) 36-41
• 27 de Vries JJ, Veen CSB, Snoek CJM, Kruip MJHA, de Maat MPM. FIBTEM clot firmness parameters correlate well with the fibrinogen concentration measured by the Clauss assay in patients and healthy subjects. Scand J Clin Lab Invest 2020; 80 (07) 600-605
• 28 Hosmer DW, Lemeshow S. Applied Logistic Regression. 2nd ed.. New York, NY: Wiley; 2000
• 29 Bercovitz RS, Shewmake AC, Newman DK. et al. Validation of a definition of excessive postoperative bleeding in infants undergoing cardiac surgery with cardiopulmonary bypass. J Thorac Cardiovasc Surg 2018; 155 (05) 2112-2124.e2
• 30 Dennhardt N, Sümpelmann R, Horke A. et al. Prevention of postoperative bleeding after complex pediatric cardiac surgery by early administration of fibrinogen, prothrombin complex and platelets: a prospective observational study. BMC Anesthesiol 2020; 20 (01) 302
• 31 Faraoni D. Definition of postoperative bleeding in children undergoing cardiac surgery with cardiopulmonary bypass: one size doesn't fit all. J Thorac Cardiovasc Surg 2018; 155 (05) 2125-2126
• 32 Mumford AD, Harris J, Plummer Z. et al. Near-patient coagulation testing to predict bleeding after cardiac surgery: a cohort study. Res Pract Thromb Haemost 2017; 1 (02) 242-251
• 33 Dimberg A, Alström U, Janiec M. Re-exploration for bleeding associated with increased incidence of the need for reintervention after coronary artery bypass graft surgery. Interact Cardiovasc Thorac Surg 2019; 28 (02) 214-221
• 34 Elassal AA, Al-Ebrahim KE, Debis RS. et al. Re-exploration for bleeding after cardiac surgery: revaluation of urgency and factors promoting low rate. J Cardiothorac Surg 2021; 16 (01) 166
• 35 Javed F, Aleysae NA, Al-Mahbosh AY. et al. Complications after surgical repair of congenital heart disease in infants. an experience from tertiary care center. J Saudi Heart Assoc 2021; 33 (04) 271-278
• 36 Ly M, Roubertie F, Belli E. et al. Continuous cerebral perfusion for aortic arch repair: hypothermia versus normothermia. Ann Thorac Surg 2011; 92 (03) 942-948 , discussion 948
• 37 Laskine-Holland M-L, Kahr WHA, Crawford-Lean L. et al. The association between cyanosis and thromboelastometry (ROTEM) in children with congenital heart defects: a retrospective cohort study. Anesth Analg 2017; 124 (01) 23-29
• 38 Miller BE, Mochizuki T, Levy JH. et al. Predicting and treating coagulopathies after cardiopulmonary bypass in children. Anesth Analg 1997; 85 (06) 1196-1202
• 39 Williams GD, Bratton SL, Ramamoorthy C. Factors associated with blood loss and blood product transfusions: a multivariate analysis in children after open-heart surgery. Anesth Analg 1999; 89 (01) 57-64
• 40 Ural K, Owen C. Pro: The Hepcon HMS should be used instead of traditional activated clotting time (ACT) to dose heparin and protamine for cardiac surgery requiring cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2016; 30 (06) 1727-1729
• 41 Gilly G, Trusheim J. Con: The Hepcon HMS should not be used instead of traditional activated clotting time to dose heparin and protamine for cardiac surgery requiring cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2016; 30 (06) 1730-1732
• 42 Bolliger D, Maurer M, Tanaka KA. Toward optimal anticoagulation monitoring during cardiopulmonary bypass: it is still a tough “ACT”. J Cardiothorac Vasc Anesth 2020; 34 (11) 2928-2930
• 43 Abuelkasem E, Mazzeffi MA, Henderson RA. et al. Clinical impact of protamine titration-based heparin neutralization in patients undergoing coronary bypass grafting surgery. J Cardiothorac Vasc Anesth 2019; 33 (08) 2153-2160
• 44 Garvin S, FitzGerald DC, Despotis G, Shekar P, Body SC. Heparin concentration-based anticoagulation for cardiac surgery fails to reliably predict heparin bolus dose requirements. Anesth Analg 2010; 111 (04) 849-855
• 45 Shore-Lesserson L, Baker RA, Ferraris V. et al. STS/SCA/AmSECT clinical practice guidelines: anticoagulation during cardiopulmonary bypass. J Extra Corpor Technol 2018; 50 (01) 5-18
• 46 Falter F, MacDonald S, Matthews C, Kemna E, Cañameres J, Besser M. Evaluation of point-of-care ACT coagulometers and anti-Xa activity during cardiopulmonary bypass. J Cardiothorac Vasc Anesth 2020; 34 (11) 2921-2927
• 47 Jia Z, Tian G, Ren Y, Sun Z, Lu W, Hou X. Pharmacokinetic model of unfractionated heparin during and after cardiopulmonary bypass in cardiac surgery. J Transl Med 2015; 13: 45
• 48 Rijpkema M, Vlot EA, Stehouwer MC, Bruins P. Does heparin rebound lead to postoperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass?. Perfusion 2023; (e-pub ahead of print) DOI: 10.1177/02676591231199218.
• 49 Peterson JA, Maroney SA, Zwifelhofer W. et al. Heparin-protamine balance after neonatal cardiopulmonary bypass surgery. J Thromb Haemost 2018; 16 (10) 1973-1983
• 50 Görlinger K, Dirkmann D, Hanke AA. et al. First-line therapy with coagulation factor concentrates combined with point-of-care coagulation testing is associated with decreased allogeneic blood transfusion in cardiovascular surgery: a retrospective, single-center cohort study. Anesthesiology 2011; 115 (06) 1179-1191
• 51 Weber CF, Görlinger K, Meininger D. et al. Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. Anesthesiology 2012; 117 (03) 531-547
• 52 Görlinger K, Dirkmann D, Hanke AA. Potential value of transfusion protocols in cardiac surgery. Curr Opin Anaesthesiol 2013; 26 (02) 230-243
• 53 Timpa JG, O'Meara LC, Goldberg KG. et al. Implementation of a multidisciplinary bleeding and transfusion protocol significantly decreases perioperative blood product utilization and improves some bleeding outcomes. J Extra Corpor Technol 2016; 48 (01) 11-18
• 54 Chan AK, Leaker M, Burrows FA. et al. Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass. Thromb Haemost 1997; 77 (02) 270-277
• 55 Durandy Y. Use of blood products in pediatric cardiac surgery. Artif Organs 2015; 39 (01) 21-27
• 56 Brown AC, Hannan RT, Timmins LH, Fernandez JD, Barker TH, Guzzetta NA. Fibrin network changes in neonates after cardiopulmonary bypass. Anesthesiology 2016; 124 (05) 1021-1031
• 57 Chandler WL, Velan T. Secretion of tissue plasminogen activator and plasminogen activator inhibitor 1 during cardiopulmonary bypass. Thromb Res 2003; 112 (03) 185-192
• 58 Sniecinski RM, Chandler WL. Activation of the hemostatic system during cardiopulmonary bypass. Anesth Analg 2011; 113 (06) 1319-1333
• 59 Kern FH, Morana NJ, Sears JJ, Hickey PR. Coagulation defects in neonates during cardiopulmonary bypass. Ann Thorac Surg 1992; 54 (03) 541-546
• 60 Despotis G, Avidan M, Eby C. Prediction and management of bleeding in cardiac surgery. J Thromb Haemost 2009; 7 (Suppl. 01) 111-117
• 61 Makar AB, McMartin KE, Palese M, Tephly TR. Formate assay in body fluids: application in methanol poisoning. Biochem Med 1975; 13: 117-126
• 62 Tanaka KA, Egan K, Szlam F. et al. Transfusion and hematologic variables after fibrinogen or platelet transfusion in valve replacement surgery: preliminary data of purified lyophilized human fibrinogen concentrate versus conventional transfusion. Transfusion 2014; 54 (01) 109-118
• 63 Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion 2014; 54 (05) 1389-1405 , quiz 1388
• 64 Bolliger D, Szlam F, Molinaro RJ, Rahe-Meyer N, Levy JH, Tanaka KA. Finding the optimal concentration range for fibrinogen replacement after severe haemodilution: an in vitro model. Br J Anaesth 2009; 102 (06) 793-799
• 65 Kindo M, Hoang Minh T, Gerelli S. et al. Plasma fibrinogen level on admission to the intensive care unit is a powerful predictor of postoperative bleeding after cardiac surgery with cardiopulmonary bypass. Thromb Res 2014; 134 (02) 360-368
• 66 Erdoes G, Dietrich W, Stucki MP. et al. Short-term recovery pattern of plasma fibrinogen after cardiac surgery: a prospective observational study. PLoS One 2018; 13 (08) e0201647
• 67 Colin-Bracamontes I, Pérez-Calatayud ÁA, Carrillo-Esper R. et al. Observational safety study of Clottafact^® fibrinogen concentrate: real-world data in Mexico. Clin Drug Investig 2020; 40 (05) 485-491
• 68 Djambas Khayat C, Lohade S, D'Souza F. et al. Efficacy and safety of fibrinogen concentrate for on-demand treatment of bleeding and surgical prophylaxis in paediatric patients with congenital fibrinogen deficiency. Haemophilia 2021; 27 (02) 283-292
• 69 Fassl J, Lurati Buse G, Filipovic M. et al. Perioperative administration of fibrinogen does not increase adverse cardiac and thromboembolic events after cardiac surgery. Br J Anaesth 2015; 114 (02) 225-234
• 70 Waldén K, Jeppsson A, Nasic S, Karlsson M. Fibrinogen concentrate to cardiac surgery patients with ongoing bleeding does not increase the risk of thromboembolic complications or death. Thromb Haemost 2020; 120 (03) 384-391
• 71 Romlin BS, Söderlund F, Wåhlander H, Nilsson B, Baghaei F, Jeppsson A. Platelet count and function in paediatric cardiac surgery: a prospective observational study. Br J Anaesth 2014; 113 (05) 847-854
• 72 Gautam NK, Pierre J, Edmonds K. et al. Transfusing platelets during bypass rewarming in neonates improves postoperative outcomes: a randomized controlled trial. World J Pediatr Congenit Heart Surg 2020; 11 (01) 71-76
• 73 Váradi K, Negrier C, Berntorp E. et al. Monitoring the bioavailability of FEIBA with a thrombin generation assay. J Thromb Haemost 2003; 1 (11) 2374-2380
• 74 Munlemvo DM, Tobias JD, Chenault KM, Naguib A. Prothrombin complex concentrates to treat coagulation disturbances: an overview with a focus on use in infants and children. Cardiol Res 2022; 13 (01) 18-26
• 75 Ortmann E, Besser MW, Sharples LD. et al. An exploratory cohort study comparing prothrombin complex concentrate and fresh frozen plasma for the treatment of coagulopathy after complex cardiac surgery. Anesth Analg 2015; 121 (01) 26-33
• 76 Smith MM, Schroeder DR, Nelson JA. et al. Prothrombin complex concentrate vs plasma for post-cardiopulmonary bypass coagulopathy and bleeding: a randomized clinical trial. JAMA Surg 2022; 157 (09) 757-764
• 77 Jooste EH, Machovec KA, Einhorn LM. et al. 3-Factor prothrombin complex concentrates in infants with refractory bleeding after cardiac surgery. J Cardiothorac Vasc Anesth 2016; 30 (06) 1627-1631
• 78 Siemens K, Sangaran DP, Hunt BJ, Murdoch IA, Tibby SM. Strategies for prevention and management of bleeding following pediatric cardiac surgery on cardiopulmonary bypass: a scoping review. Pediatr Crit Care Med 2018; 19 (01) 40-47
• 79 Harnish J, Beyer K, Collins J. Anticoagulation strategies in pediatric cardiopulmonary bypass, weight-based vs. concentration-based approaches. J Extra Corpor Technol 2022; 54 (02) 153-160
• 80 Guzzetta NA, Monitz HG, Fernandez JD, Fazlollah TM, Knezevic A, Miller BE. Correlations between activated clotting time values and heparin concentration measurements in young infants undergoing cardiopulmonary bypass. Anesth Analg 2010; 111 (01) 173-179
• 81 Gruenwald C, de Souza V, Chan AK, Andrew M. Whole blood heparin concentrations do not correlate with plasma antifactor Xa heparin concentrations in pediatric patients undergoing cardiopulmonary bypass. Perfusion 2000; 15 (03) 203-209
• 82 Linder JR, Andrade LM, Giglia TM, Glatz AC. New options for anticoagulation in congenital and pediatric acquired heart disease. Prog Pediatr Cardiol 2020; 59: 101301