1.
Defining the role of recombinant activated factor VII in pediatric cardiac surgery: where should we go from here?
Warren OJ, Rogers PL, Watret AL, de Wit KL, Darzi AW, Gill R, Athanasiou T
Pediatric Critical Care Medicine. 2009;10((5):):572-82.
Abstract
OBJECTIVES Postoperative hemorrhage is a recognized complication of pediatric cardiac surgery. Both the immature coagulation system and increased susceptibility to hemodilution increase the likelihood of pediatric patients developing coagulopathy when compared with adult counterparts. Treatment options remain limited. Recombinant factor VII (rFVIIa) is a hemostatic agent increasingly used to reduce hemorrhage in other surgical settings, the role of which is unclear in this population. This article systematically reviews the published literature on the use of rFVIIa in pediatric cardiac surgery. DATA SOURCES AND STUDY SELECTION A systematic literature search identified reports of rFVIIa administration in pediatric patients undergoing cardiac surgery. Where possible, individual patient-specific data were extracted and pooled statistical analysis was performed. DATA EXTRACTION AND SYNTHESIS Twenty-nine articles reporting on the administration of rFVIIa to 169 patients were identified. rFVIIa has been administered to patients with predefined congenital abnormalities of hemostasis to arrest hemorrhage refractory to other interventions and prophylactically in the hope of reducing blood loss. Treatment regimens vary widely, in terms of both first and cumulative dose. Data on chest tube blood loss and two markers of coagulation were pooled and analyzed, and significant improvements were demonstrated. Mortality was 4.4% for the entire cohort but 20% of patients on extracorporeal membrane oxygenation suffered significant thromboembolic complications. CONCLUSIONS rFVIIa has an increasingly accepted role in the management of patients with congenital coagulopathies undergoing major surgery. However, randomized trials are required to define the role of rFVIIa as an adjunct to control major hemorrhage in the pediatric cardiac surgical population. Any future work must focus not only on benefits but also on patient safety, particularly, risk of morbid thromboembolic complication.
2.
Elective administration in infants of low-dose recombinant activated factor VII (rFVIIa) in cardiopulmonary bypass surgery for congenital heart disease does not shorten time to chest closure or reduce blood loss and need for transfusions: a randomized, double-blind, parallel group, placebo-controlled study of rFVIIa and standard haemostatic replacement therapy versus standard haemostatic replacement therapy
Ekert H, Brizard C, Eyers R, Cochrane A, Henning R
Blood Coagulation & Fibrinolysis. 2006;17((5):):389-95.
Abstract
We investigated the effectiveness of prophylactic administration of recombinant activated factor VII (rFVIIa) for cardiopulmonary bypass surgery in children under 1 year old with congenital heart disease (CHD) in a double-blinded, placebo-controlled study. The rFVIIa dose was 40 microg/kg and all patients also received standard haemostatic replacement therapy. The primary endpoint was the time to chest closure from neutralization of heparin with protamine sulphate as this could be most objectively and accurately measured during surgery. Secondary endpoints were volumes of transfused blood, platelet concentrates and fresh-frozen plasma. All adverse events were recorded. In the intention-to-treat analysis there were 76 patients (40 in rFVIIa group and 36 in placebo group). The demographics and severity of CHD were similar in both groups. No benefit of rFVIIa prophylaxis was found in the time to chest closure, which was significantly prolonged in the rFVIIa group (rFVIIa mean +/- SE, 98. 8 +/- 27. 27 versus 55. 3 +/- 29. 15, P = 0. 0263). In the 41 patients available for a follow-up visit 6 weeks after discharge, the chest closure time was also prolonged in the rFVIIa group (P = 0. 0515). There were no significant differences in the secondary endpoints. Adverse events were similar in both groups.
3.
Factor XIII prevents development of myocardial edema in children undergoing surgery for congenital heart disease
Wozniak G, Noll T, Akinturk H, Thul J, Muller M
Annals of the New York Academy of Sciences. 2001;936:617-20.
Abstract
In a prospective investigation of perioperative cardiac edema formation requiring a delayed sternal closure, we identified thrombin increase combined with a simultaneous decrease of factor XIII as a probable cause. After experimental studies additionally revealed that factor XIII could protect endothelial barrier function, we did another prospective randomized trial in which factor XIII or placebo was preoperatively substituted. The substitution finally showed distinct effects minimizing the incidence of myocardial swelling. Therefore, the clinical application of factor XIII may have a valuable therapeutic benefit in cases of leakage syndrome during extracorporeal circulation in congenital heart surgery.