title: Effect of heparin loading during congenital heart operation on thrombin generation and blood loss.
abstract: BACKGROUND
  The heparin protocols used during cardiopulmonary bypass (CPB) in children undergoing surgical repair for congenital heart disease are extrapolated from adult data. Studies are needed that assess the optimal heparin dosing in these children, whose heparin clearance is increased compared with that in adults.
  
  
  METHODS
  We assessed the effects of two commonly used doses of heparin in the prime solution at the start of CPB operation on plasma heparin levels, on thrombin production (thrombin-antithrombin III complexes, prothrombin fragment 1 + 2, D-dimer, and antithrombin III), and on the risk of hemorrhage. Before CPB, 48 children with congenital heart disease received heparin intravenously in a loading dose of 300 U/kg, followed by either 1 U/mL of heparin in the prime (low-dose group: 22 patients-acyanotic, 9; cyanotic, 13) or 3 U/mL of heparin in the prime (group: high-dose, 26 patients-acyanotic, 15; cyanotic, 11).
  
  
  RESULTS
  In all patients, CPB resulted in the generation of thrombin. The duration of CPB was a significant covariate factor for heparin levels (p = 0.002), thrombin production (p < 0.001), and postoperative blood loss (p < 0.001). In the patients in the high-dose group, the total heparin dose and the plasma heparin levels were higher (p = 0.0005 and 0.005, respectively) and the D-dimer levels tended to be lower (p = 0.06). The postoperative blood loss was higher in the cyanotic patients (p = 0.02; both high-dose and low-dose groups), with 2 cyanotic patients (1 in low-dose group, 1 in high-dose group) requiring reoperation, one of whom subsequently died. The increased heparin dose had no significant effect on the rate or volume of postoperative blood loss.
  
  
  CONCLUSIONS
  Increasing the heparin dose in the prime solution from 1 to 3 U/mL increased the plasma heparin levels and showed a trend toward reducing the postoperative laboratory values indicative of fibrinolysis. Thrombin generation during CPB and the incidence of postoperative hemorrhage were not significantly altered. Larger randomized trials are needed to determine the optimal heparin-dosing regimen in patients with congenital heart disease.
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: S O
authors.initials: SO
authors.lastname: Turner-Gomes
authors.forename: E P
authors.initials: EP
authors.lastname: Nitschmann
authors.forename: G R
authors.initials: GR
authors.lastname: Norman
authors.forename: M E
authors.initials: ME
authors.lastname: Andrew
authors.forename: W G
authors.initials: WG
authors.lastname: Williams
mesh_terms: D000293:Adolescent; D000925:Anticoagulants / Q000008:administration & dosage*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002314:Cardioplegic Solutions; D002315:Cardiopulmonary Bypass; D002648:Child; D002675:Child, Preschool; D006330:Heart Defects, Congenital / Q000601:surgery*; D006438:Hemodilution; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D010446:Peptide Fragments / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D013917:Thrombin / Q000096:biosynthesis
chemical_list: D000925:Anticoagulants; D002314:Cardioplegic Solutions; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D006493:Heparin; D013917:Thrombin