Coagulation and Fibrinolytic Profile of Paediatric Patients Undergoing Cardiopulmonary Bypass

Abstract

SummaryThe 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, XI, XII, prekallikrein, protein C, protein S, antithrombin (AT), heparin cofactor II, α2-macroglobulin, plasminogen, α2-antiplas- min, 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, α2AP) 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.

Factor V Leiden Protects Against Blood Loss and Transfusion After Cardiac Surgery

“…Hemodilution occurs during CPB, and factor V levels fall as low as 30% to 40% of normal. 21,22 Whether FVL is affected by hemodilution to a greater or lesser extent than wild-type factor V is unknown and worthy of speculation. Also, it is not known how protein C resistance conferred by FVL is affected by dilution of CPB, since dilution alone significantly alters coagulation.…”

Risk, Clinical Features, and Outcomes of Thrombosis Associated With Pediatric Cardiac Surgery

“…The initiation of cardiopulmonary bypass can result in a further 50% decrease in circulating coagulation factors and antithrombin levels, in addition to a 70% drop in platelet counts. 24 In addition to the newly acquired hypercoagulable state and functional resistance to anticoagulation, physical factors increase the risk of thrombosis in this population. The presence of an indwelling access line is generally considered one of the most important risk factors for thrombosis in pediatric patients, and Ϸ20% of patients with an indwelling access line will develop a related thrombus.…”

“…Neonates have developmental immaturity of their coagulation and fibrinolytic system, 3 including lower sensitivity to anticoagulation and decreased fibrinolytic system activity. 1,24 Fibrinogen levels and white blood cell count in the postoperative period are important observations that may reflect the level of activity of the overall fibrinolytic system and should be investigated further as factors associated with requirement for higher anticoagulation doses. For patients with persistent thrombi, long-term complications are frequent and manifest as postthrombotic syndrome.…”

Blood Conservation in Pediatric Cardiac Surgery

“…Like hemodilution, consumption can be limited by accurate plasma concentrations of heparin. 42 The activated coagulation time (ACT) often used during CPB does not account for factors unrelated to heparin activity, including hemodilution, hypothermia and platelet activation. ACT does not allow for accurate heparin monitoring, particularly in small children.…”