Original Article| Volume 30, ISSUE 5, P1184-1189, October 2016

Download started.


Heparin Reversal After Cardiopulmonary Bypass: Are Point-of-Care Coagulation Tests Interchangeable?


      Protamine is used to neutralize heparin after patient separation from cardiopulmonary bypass (CPB). Different bedside tests are used to monitor the adequacy of heparin neutralization. For this study, the interchangeability of the activated coagulation time (ACT) and thromboelastometry (ROTEM; Tem Innovations GmbH, Basel, Switzerland) clotting time (CT) ratios in children undergoing cardiac surgery was assessed.


      Single-center, retrospective, cohort study between September 2010 and January 2012.


      University children’s hospital.


      The study comprised children 0 to 16 years old undergoing elective cardiac surgery with CPB. Exclusion criteria were preoperative coagulopathy, Jehovah’s witnesses, and children in a moribund condition (American Society of Anesthesiologists score 5).



      Measurements and Main Results

      After heparin neutralization with protamine, the ratio between ACT, with and without heparinase, and the CT measured with INTEM/HEPTEM (intrinsic test activated with ellagic acid was performed without heparinase [INTEM] and with heparinase [HEPTEM]) using tests of ROTEM were calculated. Agreement was evaluated using Cohen’s kappa statistics, Passing-Bablok regression, and Bland-Altman analysis. Among the 173 patients included for analysis, agreement between both tests showed a Cohen’s kappa statistic of 0.06 (95% CI: -0.02 to 0.14; p = 0.22). Bland-Altman analysis showed a bias of 0.01, with a standard deviation of 0.13, and limits of agreement between -0.24 and 0.26. Passing-Bablok regression showed a systematic difference of 0.40 (95% CI: 0.16-0.59) and a proportional difference of 0.61 (95% CI: 0.42-0.86). The residual standard deviation was 0.11 (95% CI: -0.22 to 0.22), and the test for linearity showed p = 0.10.


      ACT, with or without heparinase, and the INTEM/HEPTEM CT ratios are not interchangeable to evaluate heparin reversal after pediatric patient separation from CPB. Therefore, the results of these tests should be corroborated with the absence/presence of bleeding and integrated into center-specific treatment algorithms.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Cardiothoracic and Vascular Anesthesia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Paparella D.
        • Brister S.J.
        • Buchanan M.R.
        Coagulation disorders of cardiopulmonary bypass: A review.
        Intens Care Med. 2004; 30: 1873-1881
        • Rasoli S.
        • Zeinah M.
        • Athanasiou T.
        • et al.
        Optimal intraoperative anticoagulation strategy in patients undergoing off-pump coronary artery bypass.
        Interact Cardiovasc Thorac Surg. 2012; 14: 629-633
        • Levy J.H.
        • Tanaka K.A.
        Anticoagulation and reversal paradigms: Is too much of a good thing bad?.
        Anesth Analg. 2009; 108: 692-694
        • Despotis G.
        • Avidan M.
        • Eby C.
        Prediction and management of bleeding in cardiac surgery.
        J Thromb Haemost. 2009; 7: 111-117
        • Jenkins K.J.
        • Gauvreau K.
        • Newburger J.W.
        • et al.
        Consensus-based method for risk adjustment for surgery for congenital heart disease.
        J Thorac Cardiovasc Surg. 2002; 123: 110-118
        • DiNardo J.A.
        • Zvara D.A.
        Management of cardiopulmonary bypass.
        in: Wiley J. Anesthesia for cardiac surgery. Blackwell Publishing, Malden, MA2007: 323-374
        • Mittermayr M.
        • Velik-Salchner C.
        • Stalzer B.
        • et al.
        Detection of protamine and heparin after termination of cardiopulmonary bypass by thrombelastometry (ROTEM): Results of a pilot study.
        Anesth Analg. 2009; 108: 743-750
        • Kwiecein R.
        • Knopp-Schneider A.
        • Blettner M.
        Concordance analysis: Part 16 of a series on evaluation of scientific publications.
        Dtsch Artzebl Int. 2011; 108: 515-521
        • Bowers J.
        • Ferguson J.J.
        Use of the activated clotting time in anticoagulation monitoring of intravascular procedures.
        Tex Heart Inst J. 1993; 20: 258-263
        • Murray D.J.
        • Brosnahan W.J.
        • Pennell B.
        • et al.
        Heparin detection by the activated clotting time: A comparison of the sensitivity of coagulation tests and heparin assays.
        J Cardiothorac Vasc Anest. 1997; 11: 24-28
        • Theusinger O.M.
        • Nürnberg J.
        • Asmis L.M.
        • et al.
        Rotation thromboelastometry (ROTEM) stability and reproducibility over time.
        Eur J Cardiothorac Surg. 2010; 37: 677-683
        • Ortmann E.
        • Rubino A.
        • Altemimi B.
        • et al.
        Validation of viscoelastic coagulation tests during cardiopulmonary bypass.
        J Thromb Haemost. 2015; 13: 1207
        • Larsen O.H.
        • Fenger-Erikson C.
        • Christiansen K.
        • et al.
        Diagnostic performance and therapeutic consequences of thromboelastometry activated by kaolin versus panel of specific reagents.
        Anesthesiology. 2011; 115: 294-302
        • Andersen L.
        • Quasim I.
        • Steven M.
        • et al.
        Interoperator variability of whole blood coagulation assays: A comparison of thromboelastography and rotational thrombomboelastometry.
        J Cardiothorac Vasc Anesth. 2014; 28: 1550-1557
        • Fritsma G.A.
        • Dembitzer F.R.
        • Randhawa A.
        • et al.
        Recommendations for appropriate activated partial thromboplastin time reagent selection and utilization.
        Am J Clin Pathol. 2012; 137: 904-908
        • Dyke C.
        • Aronson S.
        • Dietrich W.
        • et al.
        Universal definition of perioperative bleeding in adult cardiac surgery.
        J Cardiothorac Vasc Surg. 2014; 146: 1458-1463
        • Romlin B.S.
        • Wåhlander H.
        • Berggren H.
        • et al.
        Intraoperative thromboelastometry is associated with reduced transfusion prevalence in pediatric cardiac surgery.
        Anesth Analg. 2011; 112: 30-36