title: Heparin Reversal After Cardiopulmonary Bypass: Are Point-of-Care Coagulation Tests Interchangeable?
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Single-center, retrospective, cohort study between September 2010 and January 2012.
  
  
  METHODS
  University children's hospital.
  
  
  METHODS
  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).
  
  
  METHODS
  None.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pediatric Intensive Care Unit, Department of Pediatrics, Queen Fabiola University Children's Hospital, Brussels, Belgium. Electronic address: ariane.willems@huderf.be.
authors.forename: Ariane
authors.initials: A
authors.lastname: Willems
authors.affiliation: Department of Anesthesiology and Intensive Care, Valeriu Ghereg State Medical and Pharmaceutical University Nicolae Testemitanu, Chisinau, Republic of Moldova.
authors.forename: Veaceslav
authors.initials: V
authors.lastname: Savan
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, MA.
authors.forename: David
authors.initials: D
authors.lastname: Faraoni
authors.affiliation: Department of Anesthesiology, University Hospital Brugmann and Queen Fabiola University Children's Hospital, Brussels, Belgium.
authors.forename: Andrée
authors.initials: A
authors.lastname: De Ville
authors.affiliation: Clinical Biology Department, University Hospital Brugmann, Brussels, Belgium.
authors.forename: Laurence
authors.initials: L
authors.lastname: Rozen
authors.affiliation: Clinical Biology Department, University Hospital Brugmann, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Demulder
authors.affiliation: Department of Anesthesiology, University Hospital Brugmann and Queen Fabiola University Children's Hospital, Brussels, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Van der Linden
mesh_terms: D000293:Adolescent; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000379:methods; D002315:Cardiopulmonary Bypass; D002648:Child; D002675:Child, Preschool; D006494:Heparin Antagonists / Q000627:therapeutic use*; D019763:Heparin Lyase / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D019095:Point-of-Care Systems; D011182:Postoperative Care / Q000379:methods*; D011479:Protamines / Q000627:therapeutic use; D012189:Retrospective Studies; D013916:Thrombelastography / Q000187:drug effects; D014914:Whole Blood Coagulation Time
chemical_list: D006494:Heparin Antagonists; D011479:Protamines; D019763:Heparin Lyase
keywords: ACT; ROTEM; anticoagulation; bleeding; blood; coagulation; congenital heart disease; pediatric; point-of-care tests