Management and monitoring of anticoagulation for children undergoing cardiopulmonary bypass in cardiac surgery

Abstract

Cardiopulmonary bypass (CPB) creates a pro-coagulant state by causing platelet activation and inflammation leading to thrombin generation and platelet dysfunction. It is associated with severe derangements in normal homeostasis resulting in both thrombotic and hemorrhagic complications. This derangement is greater in children with congenital heart disease than in adults because of the immaturity of the coagulation system, hemodilution of coagulation factors, hyperreactive platelets, and in some patients, physiologic changes associated with cyanosis. During CPB, an appropriate amount of heparin is given with the goal of minimizing the risk of thrombosis and platelet activation and at the same time reducing the risk of bleeding from over anticoagulation. In young children, this balance is more difficult to achieve because of inherent characteristics of the hemostatic system in these patients. Historically, protocols for heparin dosing and monitoring in children have been adapted from adult protocols without re-validation for children. Extreme hemodilution of coagulation factors and platelets in young children affects the accuracy of anticoagulation monitoring in children. The activated clotting time does not correlate with plasma levels of heparin. In addition, recent studies suggest that children need larger doses of heparin than adults, because they have lower antithrombin levels, and they metabolize heparin more rapidly. Preliminary studies demonstrated that the use of individualized heparin and protamine monitoring and management in children is associated with reduced platelet activation and dysfunction and improved clinical outcomes. However, this review article clearly establishes that further studies are necessary to obtain evidence-based protocols for the proper management of anticoagulation of children undergoing cardiopulmonary bypass.

Figure 1.

Association between CPB, anticoagulation, bleeding, and thrombosis. (AT, antithrombin; CHD, Congenital heart disease; ACT, Activated clotting time; INR, international normalized ratio; aPTT, activated partial thromboplastin time; IL, interleukin; TNFα, Tumor necrosis factor.)

Figure 2.

Lack of association between heparin levels and ACT in pediatric patients undergoing cardiopulmonary bypass for cardiac surgery. There is no correlation between heparin concentration and ACT observed. Reprinted with permission from “Andrew M, MacIntyre B, MacMillan J, et al. Heparin therapy during cardiopulmonary bypass in children requires ongoing quality control. Thromb Haemost. 1993;70:940”.

Figure 3.

Effect of HMS monitoring (HC) vs. weight based heparin management (C) on blood loss in pediatric patients. Blood loss during the first 24 postoperative hours was significantly reduced in group HC. Reprinted with permission from “Codispoti M, Ludlam CA, Simpson D, Mankad PS. Individualized heparin and protamine management in infants and children undergoing cardiac operations. Ann Thorac Surg. 2001;71(3):922–7, Figure 5”.