Appendix II

Off-Label rFVIIa Administration to Children Who Underwent Cardiac Surgery or Were on Mechanical Circulatory Support (ECMO or Ventricular Assist Device)

Efficacy:

Prospective randomized trials

1. Ekert H, Brizard C, Eyers R, Cochrane A, Henning R. 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. Blood Coagul Fibrinolysis 2006;17:389-95

Retrospective reviews and case reports

1. Witmer CM, Huang Y, Lynch K, Raffini LJ, Shah S. Off-label recombinant factor VIIa use and thrombosis in children: a multi-center cohort study. J Pediatr 2011;158:820-5

2. Pychynska-Pokorska M, Pagowska-Klimek I, Krajewski W, Moll JJ. Use of recombinant activated factor VII for controlling refractory postoperative bleeding in children undergoing cardiac surgery with cardiopulmonary bypass. J Cardiothor Vasc Anesth 2011;25:987-94

3. Chuansumrit A, Teeraratkul S, Wanichkul S, Treepongkaruna S, Sirachainan N, Pakakasama S, Nuntnarumit P, Hongeng S, rFVIIa Study Group. Recombinant-activated factor VII for control and prevention of hemorrhage in nonhemophilic pediatric patients. Blood Coagul Fibrinolysis 2010;21:354-62

4. Karsies TJ, Nicol KK, Galantowicz ME, Stephens JA, Kerlin BA. Thrombotic risk of recombinant factor seven in pediatric cardiac surgery: a single institution experience. Ann Thorac Surg 2010;89:570-6

5. Niebler RA, Punzalan RC, Marchan M, Lankiewicz MW. Activated recombinant factor VII for refractory bleeding during extracorporeal membrane oxygenation. Pediatr Crit Care Med 2010;11:98-102

6. Walker A, Davidson M, Chalmers E. Use of activated recombinant factor VII in pediatric extracorporeal membrane oxygenation. Pediatr Crit Care Med 2010;11:537-8

7. Schneider AG, Perez M, Tozzi P, Voirol P, Schoettker P, Angelillo-Scherrer A, Cotting J, Von Segesser L, Eggimann P. Recombinant factor VIIa for intractable life-threatening bleeding in patients with circulatory assist devices. Intensive Care Med 2010;36:1620–1

8. Alten JA, Benner K, Green K, Toole B, Tofil NM, Winkler MK. Pediatric off-label use of recombinant factor VIIa. Pediatrics 2009;123:1066-72

9. Chambers NA, Andrews D, Frew E, Kelly R, Cole C. rFV11a and paediatric open-heart surgery: thrombosis in the cardiopulmonary bypass circuit in spite of adequate markers of anticoagulation. Anaesthesia 2009;64:683-6

10. Guzzetta NA, Huch S, Fernandez JD, Tosone SR, Miller BE. Use of recombinant factor VIIa for uncontrolled bleeding in neonates after cardiopulmonary bypass. Paediatr Anaesth 2009;19:364-70

11. Kylasam S, Mos K, Fijtin S, Webster B, Chard R, Egan J. Recombinant activated factor VII following pediatric cardiac surgery. J Intensive Care Med 2009;24:116-21

12. Warren OJ, Rogers PLB, Watret AL, de Wit KL, Darzi AW, Gill R, Athanasiou T. Defining the role of recombinant activated factor VII in pediatric cardiac surgery: where should we go from here? Pediatr Crit Care Med 2009;10:572–582

13. Jen H, Shew S. Recombinant activated factor VII use in critically ill infants with active hemorrhage. J Pediatr Surg 2008;43:2235-8

14. Herbertson M, Kenet G. Applicability and safety of recombinant activated factor VII to control non-haemophilic haemorrhage: investigational experience in 265 children. Haemophilia 2008;14:753-62

15. Preston TJ, Olshove Jr VF, Ayad O, Nicol KK, Riley JB. Novoseven use in a non-cardiac pediatric ECMO patient with uncontrolled bleeding. J Extra Corpor Technol 2008;40:123-6

16. Avci Z, Malbora B, Gokdemir M, Ozkan S, Ozbek N. Successful use of recombinant factor VIIa (NovoSeven) during cardiac surgery in a pediatric patient with congenital factor XI deficiency. Pediatr Cardiol 2008;29:220-2

17. Heller M, Lau W, Pazmino-Canizares J, Brandao LR, Carcao M. A comprehensive review of rFVIIa use in a tertiary care pediatric center. Pediatr Blood Cancer 2008;50:1013-7

18. Reiter PD, Valuck RJ, Taylor RS. Evaluation of off-label recombinant activated factor VII for multiple indications in children. Clin Appl Thromb Hemost 2007;13:233-40

19. Agarwal HS, Bennett JE, Churchwell KB, Christian KG, Drinkwater Jr. DC, He Y, Taylor MB. Recombinant factor seven therapy for postoperative bleeding in neonatal and pediatric cardiac surgery. Ann Thorac Surg 2007;84:161–9

20. Veldman A, Neuhaeuser C, Akintuerk H, Thul J, Gehron J, Schranz D, Michel-Behnke I. rFVIIa in the treatment of persistent hemorrhage in pediatric patients on ECMO following surgery for congenital heart disease. Paediatr Anaesth 2007;17:1176-81

21. Grizelj R, Vukovic J, Filipovic-Grcic B, Saric D, Luetic T. Successful use of recombinant activated FVII and aminocaproic acid in four neonates with life-threatening hemorrhage. Blood Coagul Fibrinolysis 2006;17:413–5

22. Davis MC, Andersen NE, Johansson P, Andersen LW. Use of thromboelastograph and factor VII for the treatment of postoperative bleeding in a pediatric patient on ECMO after cardiac surgery. J Extra Corpor Technol 2006;38:165–7

23. Brady KM, Easley RB, Tobias JD. Recombinant activated factor VII (rFVIIa) treatment in infants with hemorrhage. Paediatr Anaesth 2006;16:1042–6

24. Brose S, Sirbu H, Engel M, Kuhlen R, Autschbach R. Successful use of recombinant factor VIIa in a patient with intractable bleeding during extracorporeal membrane oxygenation. Thorac Cardiovasc Surg 2005;53:389–90

25. Dominguez TE, Mitchell M, Friess SH, Huh JW, Manno CS, Ravishankar C, Gaynor JW, Tabbutt S. Use of recombinant factor VIIa for refractory hemorrhage during extracorporeal membrane oxygenation. Pediatr Crit Care Med 2005;6:348-51

26. Razon Y, Erez E, Vidne B, Birk E, Katz J, Tamari H, Dagan O. Recombinant factor VIIa (NovoSeven) as a hemostatic agent after surgery for congenital heart disease. Paediatr Anaesth 2005;15:235-40

27. Yilmaz BT, Alioglu B, Ozyurek E, Akay HT, Mercan S, Ozbek N. Successful use of recombinant factor VIIa (NovoSeven) during cardiac surgery in a pediatric patient with Glanzmann thrombasthenia. Pediatr Cardiol 2005;26:843-5

28. Wittenstein B, Ng C, Ravn H, Goldman A. Recombinant factor VII for severe bleeding during extracorporeal membrane oxygenation following open heart surgery. Pediatr Crit Care Med 2005;6:473–6

29. Velik-Salchner C, Sergi C, Fries D, Moser P, Streif W, Kolbitsch C. Use of recombinant factor VIIa (Novoseven®) in combination with other coagulation products led to a thrombotic occlusion of the truncus brachiocephalicus in a neonate supported by extracorporal membrane oxygenation. Anesth Analg 2005;101:924

30. Tofil NM, Winkler MK, Watts RG, Noonan J. The use of recombinant factor VIIa in a patient with Noonan syndrome and life-threatening bleeding. Pediatr Crit Care Med 2005;6:352–4

31. Tobias JD, Simsic JM, Weinstein S, Schechter W, Kartha V, Michler R. Recombinant factor VIIa to control excessive bleeding following surgery for congenital heart disease in pediatric patients. J Intensive Care Med 2004;19:270-3

32. Egan JR, Lammi A, Schell DN, Gillis J, Nunn GR. Recombinant activated factor VII in paediatric cardiac surgery. Intensive Care Med 2004;30:682-5

33. Verrijckt A, Proulx F, Morneau S, Vobecky S. Activated recombinant factor VII for refractory bleeding during extracorporeal membrane oxygenation. J Thorac Cardiovasc Surg 2004;127:1812–3

34. Pychynska-Pokorska M, Moll JJ, Krajewski W, Jarosik P. The use of recombinant coagulation factor VIIa in uncontrolled postoperative bleeding in children undergoing cardiac surgery with cardiopulmonary bypass. Pediatr Crit Care Med 2004;5:246–50

35. Leibovitch L, Kenet G, Mazor K, Matok I, Vardi A, Barzilay Z, Paret G. Recombinant activated factor VII for life-threatening pulmonary hemorrhage after pediatric cardiac surgery. Pediatr Crit Care Med 2003;4:444-6

36. Tobias JD, Groeper K, Berkenbosch JW. Preliminary experience with the use of recombinant factor VIIa to treat coagulation disturbances in pediatric patients. South Med J 2003;96:12–6

37. Tobias JD, Berkenbosch JW, Russo P. Recombinant factor VIIa to treat bleeding after cardiac surgery in an infant. Pediatr Crit Care Med 2003;4:49–51

38. Aldouri M. The use of recombinant factor VIIa in controlling surgical bleeding in nonhaemophiliac patients. Pathophysiol Haemost Thromb 2002;32:41–6

39. Sheth S, Dimichele D, Lee M, Lamour J, Quaegebeur J, Hsu D, Addonizio L. Heart transplant in a factor VIII-deficient patient with a high-titre inhibitor: perioperative management using high-dose continuous infusion factor VIII and recombinant factor VIIa. Haemophilia 2001;7:227–32

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