Pharmacological and Clinical Factors Associated with Thrombosis in Pediatric Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass.

摘要

Postoperative thrombosis in children undergoing cardiac surgery with cardiopulmonary bypass (CPB) is a frequent, under-diagnosed and clinically detrimental complication. The majority of known risk factors for thrombosis in this context are non-modifiable clinical correlates (notably younger age at surgery and cyanosis). We sought to identify modifiable physiological risk factors for post-operative thrombosis after pediatric cardiac surgery to inform the development of thromboprophylaxis strategies.;Pediatric patients were prospectively enrolled before cardiac surgery with CPB in an observational cohort study. Children <1 year old and cyanotic patients were oversampled, and all subjects had comprehensive serial laboratory assessment of hemostatic status and standardized vascular ultrasound for surveillance of post-operative thrombosis. Of 250 enrolled patients (248 completed study, 55% <1 year old, 25% cyanotic), post-operative thrombosis was diagnosed in 64 (26%) vs. 10% in 755 control patients (p<0.001). Clinical evaluation alone missed 59% of all post-operative thrombi and 20% of clinically significant thrombi.;Preoperatively, children with heart disease had important hematological abnormalities resulting in cellular activation, a balanced coagulopathy and an altered response to heparin, the primary thromboprophylaxis agent used during CPB. While these abnormalities were associated with developmental immaturity of the coagulation system to some extent, they were also exacerbated by a higher degree of cardiac insufficiency, congestive hepatopathy and inflammation. We found large between-patient differences in response to heparin, which were not accommodated by current clinical protocols. This left a substantial proportion of patients improperly anticoagulated during CPB, resulting in an inability to attenuate the severe physiological response to CPB characterized by hemodilution, inflammatory cytokine release, leukocyte and platelet activation, and thrombin generation. Multivariable factors associated with post-operative thrombosis in these patients included worsened cardiac insufficiency in the pre- and postoperative period. However, blood antithrombin levels, individual response to heparin, intraoperative anticoagulation activity, as well as heparin and protamine management were the critical factors associated with post-operative thrombosis.;In summary, children undergoing cardiac surgery with CPB are at a substantial risk of post-operative thrombosis, and current reliance on clinical evaluation is inefficient in preventing and identifying those thrombi. Many classical clinical risk factors for postoperative thrombosis can be translated into physiological risk factors amenable to thromboprophylaxis strategies which should be individualized according to both preoperative clinical factors and heparin sensitivity.