Defining the role of recombinant activated factor VII in pediatric cardiac surgery: Where should we go from here?*

Abstract

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.

Off-Label Use of Recombinant Factor VIIa in Pediatric Patients

“…The reduction in blood product administration is consistent with reports from observational studies that have demonstrated reduction in blood product requirements in pediatric patients treated with rFVIIa for uncontrolled hemorrhage 8,16,17 and studies in surgical patients that have demonstrated reductions in blood loss after rFVIIa administration. 11,12,17 Despite the observed reduction in transfusion requirements, it is difficult to make conclusions regarding the efficacy of rFVIIa from our data.…”

“…11,12,17 Despite the observed reduction in transfusion requirements, it is difficult to make conclusions regarding the efficacy of rFVIIa from our data. Other interventions used at the same time as rFVIIa administration may account for the reduction in blood product usage and subjective bleeding assessment, and no control group is available for comparison.…”

“…A systematic review of rFVIIa use in pediatric cardiac surgery demonstrated a significant reduction in blood loss after rFVIIa administration, although it noted that the published literature was small and mostly based upon retrospective and noncomparative reports. 17 A recently published retrospective study of 90 pediatric patients who received rFVIIa for uncontrolled postoperative hemorrhage after cardiac surgery for congenital heart disease also demonstrated a reduction in blood loss and transfusion requirements after rFVIIa and found that reexploration for bleeding was avoided in ∼80% of cases. 24 All patients in this study underwent transthoracic echocardiogram and clinical examination, and no cases of thrombosis were detected.…”

“…[2][3][4] Until recently, there have been few data on off-label use of rFVIIa in pediatric patients, and most have been limited to single case reports [5][6][7] and small or single-center case series, 8,9 including in cardiac surgery, [10][11][12] trauma, 13 and neurosurgery. [14][15][16] There are important differences between pediatric and adult patients with regard to their coagulation system and risk of thromboembolism, susceptibility to bleeding after cardiopulmonary bypass, 17 and the pharmacokinetics of rFVIIa. [18][19][20] Therefore, studies specific to pediatric patients are required to establish efficacy and safety of rFVIIa administration.…”

Bleeding and Thrombotic Emergencies in Pediatric Cardiac Intensive Care

“…An analysis of 29 publications reporting the use of rFVIIa in pediatric cardiac surgical patients suggests that a reasonable initial dose is 40 to 90 ug/kg followed by a repeat dose if necessary. 44 It is important to point out that standard coagulation tests such as the PT and PTT are not useful indicators of the efficacy of rFVIIa therapy. They are plasma tests of the initiation phase of coagulation and do not provide an accurate assessment of whole blood, local hemostatic activity.…”