Hemostatic Response in Paediatric Patients Undergoing Cardiopulmonary Bypass Surgery

Abstract

This prospective, single-center cohort study aimed to evaluate the hemostatic response during and after Cardiopulmonary Bypass (CPB) surgery in a large cohort of children up to 6 years of age. Blood samples were drawn at eight time points: post-induction of anesthesia, pre-unfractionated heparin (UFH), post-UFH, post-initiation of bypass, pre-protamine, post-protamine, post-chest-closure, and 6 h post-chest-closure. As expected, all measures of the UFH effect increased significantly post-UFH bolus and decreased post-protamine administration. However, thrombin generation remained inhibited compared to baseline values despite the post-UFH reversal by protamine. We also demonstrate that residual UFH effect is not responsible for the ongoing inhibition of thrombin observed post-protamine administration. The significant increase in both free and total tissue factor pathway inhibitor levels during the CPB surgery might contribute to the persistent thrombin generation/endogenous thrombin potential inhibition post-protamine administration. This study makes a significant and novel contribution by investigating the physiological mechanisms behind the degree of thrombin inhibition by UFH and the residual levels of thrombin inhibition that continue despite protamine reversal and provides a new foundation for future interventional studies in the setting of paediatric CPB surgery.

Monitoring unfractionated heparin in children: a parallel-cohort randomized controlled trial comparing 2 dose protocols

“…[14][15][16][17]19 Only 3 studies prospectively investigated the anticoagulant response to a defined IV single UFH bolus in children, but none compared different UFH doses and none evaluated clinical outcome regarding thrombotic or bleeding complications. [21][22][23]25 HEARTCAT investigated primary UFH prophylaxis in clinically stable children who mostly had elective catheterization. Another design feature was the clear separation of UFH administration via a peripheral vein and UFH sampling via large-bore cardiac catheters.…”

“…1,[8][9][10][11] Several pediatric studies demonstrated poor correlation between UFH dose and its anticoagulant effect as assessed by various laboratory methods and poor agreement between the respective tests. [12][13][14][15][16][17][18][19][20][21][22][23][24] However, only 3 studies prospectively investigated the effect of a defined IV single bolus of UFH in children, and none of them compared different UFH dosage protocols or evaluated the clinical outcome regarding thrombotic or bleeding events. [21][22][23]25 Because UFH, given its short half-life and reversibility, will continue to be a preferred anticoagulant for children, systematic studies on monitoring UFH in children are needed.…”

Anti‐activated factor II assay for monitoring unfractionated heparin in children: results of the HEARTCAT study

“…Whereas several studies have assessed various assays (APTT, ACT, and anti-FXa) for monitoring UFH therapy in children, only three studies were prospective, and none compared different dose protocols [17][18][19][20]. Generally, agreement between various laboratory assays is poor in children [11,13,18,22].…”

“…Whereas several studies have investigated the use of the activated partial thromboplastin time (APTT), the activated clotting time (ACT) and the anti-activated factor X (FXa) assays for monitoring UFH in children, there is only limited information on the use of anti-activated FII (FIIa) assays [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. In contrast to low molecular weight heparins, whose anticoagulant effect is mainly mediated by inhibiting FXa, UFH inhibits both FXa and FIIa [23].…”

Heparin concentrations in neonates during cardiopulmonary bypass: a rebuttal

“…While the authors state that the children in the Newall paper were of varying ages, and were receiving lower doses of heparin, the rationale for comparing two different patient populations receiving completely different doses of heparin is not at all clear. A more valid approach would be to compare the results of this study with a published study of the effect of heparin during CPB in children [3], While this manuscript adds to the knowledge of the effect of heparin in the setting of CPB surgery in neonates, it is extremely important that the results of this study are interpreted in view of non-physiological assays and specifically assays that do not represent the heparin concentration but effect. …”