Current use of factor concentrates in pediatric cardiac anesthesia

Abstract

Excessive bleeding following pediatric cardiopulmonary bypass is associated with increased morbidity and mortality, both from the effects of hemorrhage and the therapies employed to achieve hemostasis. Neonates and infants are especially at risk because their coagulation systems are immature, surgeries are often complex, and cardiopulmonary bypass technologies are inappropriately matched to patient size and physiology. Consequently, these young children receive substantial amounts of adult-derived blood products to restore adequate hemostasis. Adult and pediatric data demonstrate associations between blood product transfusions and adverse patient outcomes. Thus, efforts to limit bleeding after pediatric cardiopulmonary bypass and minimize allogeneic blood product exposure are warranted. The off-label use of factor concentrates, such as fibrinogen concentrate, recombinant activated factor VII, and prothrombin complex concentrates, is increasing as these hemostatic agents appear to offer several advantages over conventional blood products. However, recognizing that these agents have the potential for both benefit and harm, well-designed studies are needed to enhance our knowledge and to determine the optimal use of these agents. In this review, our primary objective was to examine the evidence regarding the use of factor concentrates to treat bleeding after pediatric CPB and identify where further research is required. PubMed, MEDLINE/OVID, The Cochrane Library and the Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched to identify existing studies.

Single-Center Use of Prothrombin Complex Concentrate in Pediatric Patients

“…[13][14][15][16][17][18][19] Although these advantages of 4F-PCC over FFP may be pertinent for pediatric patients, the optimal indications, dosing, frequency, and adverse effects in children are unknown due to limited experience. [20][21][22][23] Noga et al reported a retrospective experience in a cohort of 16 pediatric patients who received 4F-PCC to treat coagulation disturbances related to cardiac surgery and CPB or due to the administration of vitamin K antagonists. 22 Compared with this study, our patient population was unique because the main indication for 4F-PCC administration was perioperative coagulopathy, primarily secondary to trauma, and medical disorders rather than coagulopathy following CPB or from the administration of vitamin K antagonists.…”

Fibrinogen Supplementation and Its Indications

“…8,81 The effects of intraoperative fibrinogen substitution have been investigated in adult studies across a range of clinical settings, but data from pediatric surgical patients are scarce. 79,80,[82][83][84] In a randomized clinical trial performed in children undergoing major craniofacial or spinal surgery, intraoperative fibrinogen concentrate was administered using one of two FIBTEM MCF threshold values as a trigger, < 8 mm (conventional) or < 13 mm (early substitution), to maintain fibrinogen levels throughout surgery. 80 Early substitution led to a significant reduction in blood loss and transfusion of RBCs among children undergoing craniosynostosis surgery, although no significant differences were observed in those undergoing scoliosis surgery (►Fig.…”

“…84 Three comprehensive reviews of bleeding management during pediatric major surgery have been published in recent years. 83,87,88 All of them emphasized the benefits of goal-directed use of coagulation factors such as fibrinogen concentrate, especially when guided by viscoelastic assays. A meta-analysis of 14 randomized clinical trials involving 1,035 adult and pediatric surgical patients demonstrated that fibrinogen concentrate therapy was associated with reduced bleeding and that it might reduce all-cause mortality.…”

Is there a role for von Willebrand factor/factor VIII concentrate supplementation in complex congenital heart surgery?

“…Surgical correction or palliation of complex congenital heart defects in newborns and small infants is often accompanied by severe perioperative bleeding, and almost invariably requires the use of blood components (fresh frozen plasma and platelets) and often of other procoagulant interventions, including fibrinogen concentrate, prothrombin complex concentrate, factor XIII, and even recombinant activated FVII .…”