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Semin Thromb Hemost 2017; 43(07): 682-690
DOI: 10.1055/s-0037-1603365
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Hemostasis in Pediatric Cardiac Surgery

Hanne Berg Ravn
1   Department of Cardiothoracic Anesthesiology, Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
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Publication History

Publication Date:
08 June 2017 (online)

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Abstract

The majority of children undergoing pediatric cardiac surgery with cardiopulmonary bypass require transfusion of blood products. The management of hemostasis in the pediatric population is challenging, partly due to pronounced alterations in several hemostatic parameters following cardiopulmonary bypass. Despite these marked changes being seen quite often, they are not necessarily an indication for hemostatic interventions. This review summarizes and discusses the available monitoring tests of hemostatic impairment during and following pediatric cardiac surgery. It covers standard laboratory tests, viscoelastic test, evaluation of platelet function, fibrinolysis, and the management of anticoagulation including its reversal. Interpretation of hemostatic measurements is done with due respect to the concept of developmental hemostasis, but also cyanotic heart disease, which are considered by some to be associated with an increased risk of bleeding.

Keywords

pediatric - cardiac surgery - cardiopulmonary bypass - point-of-care tests - developmental hemostasis
 

  • References

  • 1 Andreasen JB, Hvas AM, Christiansen K, Ravn HB. Can RoTEM® analysis be applied for haemostatic monitoring in paediatric congenital heart surgery?. Cardiol Young 2011; 21 (06) 684-691
    CrossrefPubMedGoogle Scholar
  • 2 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
    CrossrefPubMedGoogle Scholar
  • 3 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
    CrossrefPubMedGoogle Scholar
  • 4 Faraoni D, Willems A, Savan V, Demanet H, De Ville A, Van der Linden P. Plasma fibrinogen concentration is correlated with postoperative blood loss in children undergoing cardiac surgery. A retrospective review. Eur J Anaesthesiol 2014; 31 (06) 317-326
    CrossrefPubMedGoogle Scholar
  • 5 Andrew M, Paes B, Milner R. , et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70 (01) 165-172
    PubMedGoogle Scholar
  • 6 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
    PubMedGoogle Scholar
  • 7 Monagle P, Barnes C, Ignjatovic V. , et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost 2006; 95 (02) 362-372
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Ignjatovic V, Kenet G, Monagle P. ; Perinatal and Paediatric Haemostasis Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Developmental hemostasis: recommendations for laboratories reporting pediatric samples. J Thromb Haemost 2012; 10 (02) 298-300
    CrossrefPubMedGoogle Scholar
  • 9 Attard C, van der Straaten T, Karlaftis V, Monagle P, Ignjatovic V. Developmental hemostasis: age-specific differences in the levels of hemostatic proteins. J Thromb Haemost 2013; 11 (10) 1850-1854
    PubMedGoogle Scholar
  • 10 Andrew M, Paes B, Milner R. , et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72 (05) 1651-1657
    PubMedGoogle Scholar
  • 11 Williams GD, Bratton SL, Riley EC, Ramamoorthy C. Association between age and blood loss in children undergoing open heart operations. Ann Thorac Surg 1998; 66 (03) 870-875 , discussion 875–876
    CrossrefPubMedGoogle Scholar
  • 12 Miller BE, Mochizuki T, Levy JH. , et al. Predicting and treating coagulopathies after cardiopulmonary bypass in children. Anesth Analg 1997; 85 (06) 1196-1202
    CrossrefPubMedGoogle Scholar
  • 13 Andreasen JB, Pistor-Riebold TU, Knudsen IH, Ravn HB, Hvas AM. Evaluation of different sized blood sampling tubes for thromboelastometry, platelet function, and platelet count. Clin Chem Lab Med 2014; 52 (05) 701-706
    PubMedGoogle Scholar
  • 14 Ravn HB, Andreasen JB, Hvas AM. Does whole blood coagulation analysis reflect developmental haemostasis?. Blood Coagul Fibrinolysis 2016
    PubMedGoogle Scholar
  • 15 Rizza A, Ricci Z, Pezzella C. , et al. Kaolin-activated thromboelastography and standard coagulation assays in cyanotic and acyanotic infants undergoing complex cardiac surgery: a prospective cohort study. Paediatr Anaesth 2017; 27 (02) 170-180
    CrossrefPubMedGoogle Scholar
  • 16 Ternström L, Radulovic V, Karlsson M. , et al. Plasma activity of individual coagulation factors, hemodilution and blood loss after cardiac surgery: a prospective observational study. Thromb Res 2010; 126 (02) e128-e133
    CrossrefPubMedGoogle Scholar
  • 17 Gertler R, Martin K, Hapfelmeier A, Tassani-Prell P, Braun S, Wiesner G. The perioperative course of factor XIII and associated chest tube drainage in newborn and infants undergoing cardiac surgery. Paediatr Anaesth 2013; 23 (11) 1035-1041
    CrossrefPubMedGoogle Scholar
  • 18 Pekelharing J, Furck A, Banya W, Macrae D, Davidson SJ. Comparison between thromboelastography and conventional coagulation tests after cardiopulmonary bypass surgery in the paediatric intensive care unit. Int J Lab Hematol 2014; 36 (04) 465-471
    CrossrefPubMedGoogle Scholar
  • 19 Niebler RA, Gill JC, Brabant CP. , et al. Thromboelastography in the assessment of bleeding following surgery for congenital heart disease. World J Pediatr Congenit Heart Surg 2012; 3 (04) 433-438
    CrossrefPubMedGoogle Scholar
  • 20 Luddington RJ. Thrombelastography/thromboelastometry. Clin Lab Haematol 2005; 27 (02) 81-90
    CrossrefPubMedGoogle Scholar
  • 21 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
    CrossrefPubMedGoogle Scholar
  • 22 Hvas AM, Andreasen JB, Christiansen K, Ravn HB. Ex-vivo response to blood products and haemostatic agents after paediatric cardiac surgery. Blood Coagul Fibrinolysis 2013; 24 (06) 587-592
    CrossrefPubMedGoogle Scholar
  • 23 Kim JY, Shin YR, Kil HK, Park MR, Lee JW. Reference intervals of thromboelastometric evaluation of coagulation in pediatric patients with congenital heart diseases: a retrospective investigation. Med Sci Monit 2016; 22: 3576-3587
    CrossrefPubMedGoogle Scholar
  • 24 Jensen AS, Johansson PI, Idorn L. , et al. The haematocrit--an important factor causing impaired haemostasis in patients with cyanotic congenital heart disease. Int J Cardiol 2013; 167 (04) 1317-1321
    CrossrefPubMedGoogle Scholar
  • 25 Oswald E, Stalzer B, Heitz E. , et al. Thromboelastometry (ROTEM) in children: age-related reference ranges and correlations with standard coagulation tests. Br J Anaesth 2010; 105 (06) 827-835
    CrossrefPubMedGoogle Scholar
  • 26 Woulfe DYJ, Prevost N. , et al. Signal Tranduction during the Initiation, Extension, and Perputuation of Platelet Plug Formation. New York, NY: Academic Press/Elsevier Science; 2002: 197-213
    Google Scholar
  • 27 Andrew M, Kelton J. Neonatal thrombocytopenia. Clin Perinatol 1984; 11 (02) 359-391
    CrossrefPubMedGoogle Scholar
  • 28 Sitaru AG, Holzhauer S, Speer CP. , et al. Neonatal platelets from cord blood and peripheral blood. Platelets 2005; 16 (3-4): 203-210
    CrossrefPubMedGoogle Scholar
  • 29 Roschitz B, Sudi K, Köstenberger M, Muntean W. Shorter PFA-100 closure times in neonates than in adults: role of red cells, white cells, platelets and von Willebrand factor. Acta Paediatr 2001; 90 (06) 664-670
    PubMedGoogle Scholar
  • 30 Lippi G, Manzato F, Franchini M, Brocco G, Florenziani G, Guidi G. Establishment of reference values for the PFA-100 platelet function analyzer in pediatrics. Clin Exp Med 2001; 1 (01) 69-70
    CrossrefPubMedGoogle Scholar
  • 31 Ferrer-Marin F, Stanworth S, Josephson C, Sola-Visner M. Distinct differences in platelet production and function between neonates and adults: implications for platelet transfusion practice. Transfusion 2013; 53 (11) 2814-2821 , quiz 2813
    CrossrefPubMedGoogle Scholar
  • 32 Bonduel M, Frontroth JP, Hepner M, Sciuccati G, Feliú-Torres A. Platelet aggregation and adenosine triphosphate release values in children and adults. J Thromb Haemost 2007; 5 (08) 1782-1783
    CrossrefPubMedGoogle Scholar
  • 33 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
    PubMedGoogle Scholar
  • 34 Bønding Andreasen J, Hvas AM, Ravn HB. Marked changes in platelet count and function following pediatric congenital heart surgery. Paediatr Anaesth 2014; 24 (04) 386-392
    CrossrefPubMedGoogle Scholar
  • 35 Ranucci M, Carlucci C, Isgrò G, Baryshnikova E. A prospective pilot study of platelet function and its relationship with postoperative bleeding in pediatric cardiac surgery. Minerva Anestesiol 2012; 78 (05) 556-563
    PubMedGoogle Scholar
  • 36 Hofer A, Kozek-Langenecker S, Schaden E, Panholzer M, Gombotz H. Point-of-care assessment of platelet aggregation in paediatric open heart surgery. Br J Anaesth 2011; 107 (04) 587-592
    CrossrefPubMedGoogle Scholar
  • 37 Gertler R, Hapfelmeier A, Tassani-Prell P, Wiesner G, Martin K. The effect of cyanosis on perioperative platelet function as measured by multiple electrode aggregometry and postoperative blood loss in neonates and infants undergoing cardiac surgery. Eur J Cardiothorac Surg 2015; 48 (02) 301-307
    CrossrefPubMedGoogle Scholar
  • 38 Ignjatovic V, Than J, Summerhayes R. , et al. The quantitative and qualitative responses of platelets in pediatric patients undergoing cardiopulmonary bypass surgery. Pediatr Cardiol 2012; 33 (01) 55-59
    CrossrefPubMedGoogle Scholar
  • 39 Zubair MM, Bailly DK, Lantz G. , et al. Preoperative platelet dysfunction predicts blood product transfusion in children undergoing cardiac surgery. Interact Cardiovasc Thorac Surg 2015; 20 (01) 24-30
    CrossrefPubMedGoogle Scholar
  • 40 Ortmann E, Klein AA, Sharples LD. , et al. Point-of-care assessment of hypothermia and protamine-induced platelet dysfunction with multiple electrode aggregometry (Multiplate®) in patients undergoing cardiopulmonary bypass. Anesth Analg 2013; 116 (03) 533-540
    CrossrefPubMedGoogle Scholar
  • 41 Manlhiot C, Gruenwald CE, Holtby HM. , et al. Challenges with heparin-based anticoagulation during cardiopulmonary bypass in children: Impact of low antithrombin activity. J Thorac Cardiovasc Surg 2016; 151 (02) 444-450
    CrossrefPubMedGoogle Scholar
  • 42 Manlhiot C, Menjak IB, Brandão LR. , et al. Risk, clinical features, and outcomes of thrombosis associated with pediatric cardiac surgery. Circulation 2011; 124 (14) 1511-1519
    CrossrefPubMedGoogle Scholar
  • 43 Ranucci M, Baryshnikova E, Crapelli GB, Woodward MK, Paez A, Pelissero G. Preoperative antithrombin supplementation in cardiac surgery: a randomized controlled trial. J Thorac Cardiovasc Surg 2013; 145 (05) 1393-1399
    CrossrefPubMedGoogle Scholar
  • 44 Codispoti M, Ludlam CA, Simpson D, Mankad PS. Individualized heparin and protamine management in infants and children undergoing cardiac operations. Ann Thorac Surg 2001; 71 (03) 922-927 , discussion 927–928
    CrossrefPubMedGoogle Scholar
  • 45 Gruenwald CE, Manlhiot C, Chan AK. , et al. Randomized, controlled trial of individualized heparin and protamine management in infants undergoing cardiac surgery with cardiopulmonary bypass. J Am Coll Cardiol 2010; 56 (22) 1794-1802
    CrossrefPubMedGoogle Scholar
  • 46 Myles PS, Smith JA, Forbes A. , et al; ATACAS Investigators of the ANZCA Clinical Trials Network. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med 2017; 376 (02) 136-148
    CrossrefPubMedGoogle Scholar
  • 47 Ignjatovic V, Chandramouli A, Than J. , et al. Plasmin generation and fibrinolysis in pediatric patients undergoing cardiopulmonary bypass surgery. Pediatr Cardiol 2012; 33 (02) 280-285
    CrossrefPubMedGoogle Scholar
  • 48 Breuer T, Martin K, Wilhelm M. , et al. The blood sparing effect and the safety of aprotinin compared to tranexamic acid in paediatric cardiac surgery. Eur J Cardiothorac Surg 2009; 35 (01) 167-171 , author reply 171
    CrossrefPubMedGoogle Scholar
  • 49 Koster A, Faraoni D, Levy JH. Antifibrinolytic therapy for cardiac surgery: an update. Anesthesiology 2015; 123 (01) 214-221
    PubMedGoogle Scholar
  • 50 Graham EM, Atz AM, Gillis J. , et al. Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery. J Thorac Cardiovasc Surg 2012; 143 (05) 1069-1076
    CrossrefPubMedGoogle Scholar
  • 51 Martin K, Breuer T, Gertler R. , et al. Tranexamic acid versus ɛ-aminocaproic acid: efficacy and safety in paediatric cardiac surgery. Eur J Cardiothorac Surg 2011; 39 (06) 892-897
    CrossrefPubMedGoogle Scholar
  • 52 Chauhan S, Das SN, Bisoi A, Kale S, Kiran U. Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery. J Cardiothorac Vasc Anesth 2004; 18 (02) 141-143
    CrossrefPubMedGoogle Scholar
  • 53 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
    CrossrefPubMedGoogle Scholar