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Coagulation and fibrinolytic profile of paediatric patients undergoing cardiopulmonary bypass
A K Chan1, M Leaker, F A Burrows
1Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Insights
Pediatric cardiopulmonary bypass (CPB) causes significant decreases in hemostatic proteins due to hemodilution and consumption. Low heparin levels during CPB may contribute to coagulation activation in children.
Area of Science:
- Cardiovascular Surgery
- Pediatric Hematology
- Anesthesiology
Background:
- Hemostasis and heparin use during cardiopulmonary bypass (CPB) are well-studied in adults, but not children.
- Age-dependent physiological differences in hemostasis preclude direct extrapolation of adult data to pediatric populations.
Purpose of the Study:
- To investigate perioperative hemostatic system changes in pediatric patients undergoing CPB.
- To assess the impact of CPB on coagulation and fibrinolytic factors in children.
Main Methods:
- Studied 22 pediatric patients undergoing CPB.
- Assayed perioperatively various hemostatic proteins, heparin levels, and activated clotting time (ACT).
- Collected samples at multiple time points: pre-heparin, post-heparin, during and after CPB, and 24 hours post-CPB.
Main Results:
- Plasma concentrations of hemostatic proteins decreased by an average of 56% post-CPB initiation due to hemodilution.
- Coagulation (thrombin-antithrombin complexes) and fibrinolytic systems (D-dimers) showed significant activation during CPB.
- Low heparin concentrations (<2.0 units/ml in 45% of patients) were observed during CPB.
- Activated clotting time (ACT) demonstrated a poor correlation with heparin concentrations.
Conclusions:
- CPB in pediatric patients leads to global decreases in coagulation and fibrinolytic system components, primarily via hemodilution and secondarily via consumption.
- Inadequate heparinization during CPB may be a significant factor contributing to hemostatic system activation in children.
- ACT is an unreliable indicator of heparinization in pediatric CPB due to confounding factors.
Abstract:
The haemostatic system and the use of heparin during cardiopulmonary bypass (CPB) have been studied extensively in adults but not in children. Results from adult trials cannot be extrapolated to children because of age-dependent physiologic differences in haemostasis. We studied 22 consecutive paediatric patients who underwent CPB at The Hospital for Sick Children, Toronto. Fibrinogen, factors II, V, VII, VIII, IX, XII, prekallikrein, protein C, protein S, antithrombin (AT), heparin cofactor II, alpha 2-macroglobulin, plasminogen, alpha 2-antiplasmin, tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin-AT complexes (TAT), D-dimer, heparin (by both anti-factor Xa assay and protamine titration) and activated clotting time (ACT) were assayed perioperatively. The timing of the sampling was: pre heparin, post heparin, after initiation of CPB, during hypothermia, post hypothermia, post protamine reversal and 24 h post CPB. Plasma concentrations of all haemostatic proteins decreased by an average of 56% immediately following the initiation of CPB due to haemodilution. During CPB, the majority of procoagulants, inhibitors and some components of the fibrinolytic system (plasminogen, alpha 2 AP) remained stable. However, plasma concentrations of TAT and D-dimers increased during CPB showing that significant activation of the coagulation and fibrinolytic systems occurred. Mechanisms responsible for the activation of haemostasis are likely complex. However, low plasma concentrations of heparin (< 2.0 units/ml in 45% of patients) during CPB were likely a major contributing etiology. ACT values showed a poor correlation (r = 0.38) with heparin concentrations likely due to concurrent haemodilution of haemostatic factors, activation of haemostatic system, hypothermia and activation of platelets. In conclusion, CPB in paediatric patients causes global decreases of components of the coagulation and fibrinolytic systems, primarily by haemodilution and secondarily by consumption.