Antithrombin Enhancement May Improve Anticoagulation Efficiency in Infants Undergoing Cardiopulmonary Bypass for Cardiac Surgery

• Heparin dose required to achieve target Activated Clotting Time required to go on Cardiopulmonary Bypass [ Time Frame: 1hr prior to induction of anaestheisa (pre-surgery) ] [ Designated as safety issue: No ]
  Clinical Outcome Measure
• Blood product transfusions intra-operatively and for the first 24 hours following surgery [ Time Frame: 24hours post surgery ] [ Designated as safety issue: No ]
• Clinical outcomes [ Time Frame: 30 days post-surgery ] [ Designated as safety issue: No ]
  (inotropic support, ventilation, CCU stay, hospital stay, thrombosis)
• Intraoperative coagulation profile [ Time Frame: 5 hours after start of surgery ] [ Designated as safety issue: No ]
  (anti-Xa, heparin concentration, activated clotting time, CBC, antithrombin)
• Post-operative markers of platelet activation [ Time Frame: 24 and 72 hrs post surgery ] [ Designated as safety issue: No ]
  Post-operative markers of platelet activation (TAT, F1.2), fibrinolysis (d-dimer) and inflammation (CRP)
• Use of recombinant factor VIIa after surgery to control post-operative bleeding [ Time Frame: 48 hrs post surgery ] [ Designated as safety issue: No ]

The primary objective of this study is:

1. To evaluate the use of Antithrombin (AT) concentrate in infants less than one year of age undergoing cardiopulmonary bypass (CPB) for cardiac surgery

The secondary objectives of this study are:

1. To determine if the administration of AT concentrate prior to heparinization will decrease the amount of heparin required to achieve optimal anticoagulation (as defined by anti-Xa levels) during CPB
2. To determine if a decrease in activation and consumption of coagulation proteins, platelets and subsequent fibrinolysis will result in improved haemostasis following CPB
3. To determine if there will be a reduction in postoperative bleeding and associated clinical complications

• Drug: Antithrombin III
  Patients randomized to receive Antithrombin concentrate will receive a dose of AT to achieve a target value of 1.2U/ml.
• Other: Saline Placebo
  Patients randomized to the control group will receive a placebo consisting of normal saline in a volume equivalent to the volume of antithrombin the same patient in the treatment group would have received and administered by anesthesia and perfusion in the exact same manner as the AT is administered in the treatment group.

• Placebo Comparator: Control Group
  Intervention: Other: Saline Placebo
• Experimental: Active Antithrombin Group
  Intervention: Drug: Antithrombin III

Inclusion Criteria:

1. Pediatric patients < 1 year old with cardiac defect (acquired or congenital) requiring cardiac surgery
2. Planned cardiac surgery with cardiopulmonary bypass
3. Weight > 2.5kg at the time of surgery
4. Enrolment in the CATCH main study (REB#1000020203)

Exclusion Criteria:

1. Preoperative antithrombin activity > 85%
2. Prematurity < 36 weeks gestational age at birth
3. Preoperative use of systemic anticoagulant (i.e. heparin or warfarin at a therapeutic dose) for > 24 hours or at any time within the 48 hours prior to surgery
4. Any form of coagulopathy or thrombophilic disorder
5. Renal (blood creatinine - estimated GRF < 60ml/min/1.73m2) or clinical liver failure
6. Antithrombin replacement therapy prior to surgery
7. Repeat surgery (including previous ECMO/VAD support as prior surgery)
8. Patients refusal to provide open consent for re-use of study data