SINGLE CENTER EXPERIENCE ON USE OF RECOMBINANT FACTOR SEVEN FOR BLEEDING AFTER CONGENITAL HEART SURGERY.
Objective: The objective of our study is to review the use of recombinant factor seven to control bleeding in non hemophilic patients undergoing cardiac surgery for congenital heart disease.
Study Design: Retrospective case series.
Place and Duration of Study: Peads cardiac anesthesia department of Armed Forces Institute of Cardiology, Rawalpindi, from Jan 2017 to Jan 2018.
Material and Methods: Data was collected from ICU daily monitoring and treatment charts. Patients who received rFVIIa to limit post surgical bleeding were sorted out. Gender, Age, weight, disease, date of surgery, dose of factor seven, thrombotic evidence and mortality of patients who were given factor seven to control bleeding were recorded.
Results: Total 19 patients received factor seven from Jan 2017 to Jan 2018. Mean age at surgery was 6.99 years. Nine patients (47.4%) underwent total correction for Tetrollogy of fellot, three patients (15.8%) had surgical patch closure for ventricle septal defect and two patients (10.5%) had arterial switch operation for transposition of great arteries. Fourteen patients (73.7%) survived to hospital discharge. Nine patients (47.4%) received 40mcg/kg or less of rFVIIa while the remaining ten patients received up to 80mcg/kg total dose of rFVIIa post operatively. None of the patients was found to have evidence of thrombosis.
Conclusion: Post operative bleeding was found very common and challenging problem in cardiac surgery. Further prospective study over large number of patients should be done and rFVIIa should be compared with tranexamic acid transfusion and desmopressin.
Keywords: Congenital, Non-haemophilic factor, Tetrollogy.
Severe post operative bleeding is one of the major causes of morbidity in pediatric patients with congenital heart disease undergoing open heart surgeries. Bleeding requiring exploration occurs in 1% of pediatric cardiac surgery patients, and transfusion may exceed 100 ml per Kg1. Several factors are responsible for coagulation disturbances and bleeding following cardiopulmonary bypass in patients with congenital heart disease. This includes dilution during priming of pump, platelet disorder and dysfunction, premature haemostatic system in neonates, fibrinolysis, residual heparin and disseminated intravascular coagulation (DIC)2. Abnormal homeostasis and bleeding disorder is well known in children with cyanotic heart disease. These children in hypo-coagulable state related to impaired fibrinogen function3.
In 1999 Recombinant factor seven was approved for treatment of bleeding in patients with hemophilia and inhibitors of factor VIII or IX4. Activated factor VIIa plays important role in homeostasis mechanism by forming complex with tissue factor, this complex then activates factor X which induces thrombin formation5. It has been increasing because of usage of off-label in controlling excessive bleeding following trauma, surgery and extracorporeal membrane oxygenation (ECMO) support6. In cardiac surgery patients factor seven has been found to reduce transfusion requirements and chest drain output7.
The use of recombinant factor seven has less widely been reported in pediatric patients than adults. In children different non hemophilic conditions has been described that may benefit from rFVIIa to control bleeding associated with cardiac surgery, neurosurgery, DIC, liver failure and transplantation8, rFVIIa has also got some adverse effects like, the potential to cause limb ischemia, as well as pathologic thrombosis and related major neurological events9. The main objective of this study is to review the use of rFVIIa for the treatment of bleeding in nonhemophiliac pediatric patients undergoing cardiac surgery for congenital heart disease in our setup and to recommend its use in future. The objective of our study was to review the use of recombinant factor seven to control bleeding in non hemophilic patients undergoing cardiac surgery for congenital heart disease.
MATERIAL AND METHODS
A retrospective cases series conducted at Pediatric cardiac surgery operation theatre and intensive care unit Armed Forces Instititute of Cardiology (AFIC) from January 2017 to January 2018. After approval from ethical committee, we reviewed retrospectively medical record of patients undergoing congenital heart surgeries requiring cardiopulmonary bypass from Jan, 2017 to Jan 2018 in pediatric cardiac surgery ICU. Data was collected from ICU daily monitoring and treatment charts. Patients who received rFVIIa to limit post surgical bleeding were sorted out. Gender, Age, weight, disease, date of surgery, dose of factor seven, thrombotic evidence and mortality of patients who were given factor seven to control bleeding were recorded. Total 19 patients were found to receive rFVIIa. Conduct and management of cardio pulmonary bypass (CPB), surgical procedure was according to institutional guidelines and surgeon practice.
The data was analyzed by descriptive statistics (frequency, percentage, mean and standard deviation) and chi square test was used for analysis of variance. In our study p-value of less than 0.05 was considered as statistically significant. The statistical analysis was done by using SPSS version 21.
Table: Clinical variables of study participants.
###S. No###Variables###Variable value
###1.###Age (mean +- SD) years###6.99 +- 6.16
###* Total correction for tetrollogy of fellot.
###* Surgical patch closure for ventricle septal
###* Arterial switch operation for transposition
###of great arteries
###3.###rFVIIa dose <40 mcg/kg###9 (47.4%)
###4.###rFVIIa dose 40-80 mcg/kg
For the 19 patients in our study, the demographics, congenital heart defects, dose of factor seven used, thrombotic evidence and mortality was analyzed. Mean age at surgery was 6.99 years with standard deviation of 6.16 (range: 2 months-20 years) as shown in table. Nine patients (47.4%) underwent total correction for Tetrollogy of fellot, three patients (15.8%) had surgical patch closure for ventricle septal defect and two patients (10.5%) had arterial switch operation for transposition of great arteries. Fourteen patients 73.7%) survived to hospital discharge and five (26.3%) died. Nine patients (47.4%) received 40mcg/kg or less of rFVIIa while the remaining ten patients received up to 80 mcg/kg total dose of rFVIIa postoperatively. None of the patients was found to have evidence of thrombosis. A p-value was found insignificant when two doses of factor seven were compared as related to mortality.
A p-value was also found to be insignificant when effect of type of congenital heart defect was studied on mortality.
Post operative bleeding requiring massive transfusion and re-exploration is one of the major problems in patients undergoing cardiac surgery. Re-exploration and multiple transfusions are associated with increase in mortality and end organ injury10. Blood products are most commonly used for management of bleeding. Antifibrinolytic agents like tranexamic acid, has been used in our setup in cardiac surgery to reduce blood loss and need for transfusions. Factor concentrates and pharmacologic agents such as Desmopressin have been studied for control of bleeding after surgery11. In 1999 recombinant factor seven was licensed for management of bleeding in hemophilia patients with inhibitors. In these patients the standard bolus dosing varies from 90 to 120mcg/kg and repeated every two to three hours until cessation of bleeding12 and rFVIIa has been used as off label in controlling surgical bleeding.
Its first off-label use was reported in 2001 as rescue treatment of uncontrolled postoperative bleeding13. Since then there have been increasing number of cases that report off label use of rFVIIa in various clinical situations where bleeding was difficult to control such as cardiac surgery, massive trauma and obstretetrical uncontrolled bleeding14-16. The congenital cardiac anesthesia society task force recommends rFVII for refractory post CPB bleeding16. In our center use of rFVIIa occurred just few years back. It is not being frequently used in our centre to control bleeding because of limited supply and resources. The half life of rFVIIa is 2.9 hours; therefore the frequency of rFVIIa dose is every two to three hours17. In our institute rFVIIa is given at dose of 20-40 mcg/kg and repeated after one hour as required. The dose of rFVIIa in non hemophilia patients to control bleeding has not been determined; low doses have been studied and found effective.
Friederich et al found that 20mcg/kg was effective to control bleeding18. Karsies et al. noted that 30-50 mcg/kg per dose every two to three hours was effective19. In our study 47.4% of the patients received 40 mcg/kg or less and remaining received up to 80 mcg/kg. The use of rFVIIa is associated with thrombotic events. Chuansumrit et al. studied the use of rFVIIa pediatric patients for control of hemorrhage and noted adverse events. He found the total number of doses given was directly related to thrombo-embolic events20. In our study no patient had thrombosis. Our study was a retrospective with small number of patients. In future we plan to conduct study which would be prospective control trial.
Post operative bleeding was found common and challenging problem in cardiac surgery. Further prospective study over large number of patients should be done and rFVIIa should be compared with tranexamic acid transfusion and desmopressin.
CONFLICT OF INTEREST
This study has no conflict of interest to be declare by any author.
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|Publication:||Pakistan Armed Forces Medical Journal|
|Date:||Feb 28, 2018|
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