POSTER - #KU0006

A Propensity Score Matching Study on Recombinant Factor VIIa Administration for Cardiac Surgical Bleeding

Alice Campton, BA; Akshit Sharma, MD; Betsy Cotter, MD; Guangyi Gao, PhD; Jianghua He, PhD; Katy Wirtz, RN; Trip Zorn, MD; Brigid Flynn, MD
The University of Kansas Health System

BACKGROUND
• Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) was developed in the 1970’s and used clinically in the 1980’s for patients with hemophilia.¹
• Off-label use of rFVIIa for perioperative cardiac surgical bleeding has been shown to reduce bleeding,2-5 blood product administration^2,6,7 and the rate of reoperations.^5,7,8 However, the use of rFVIIa for cardiac surgical bleeding has been associated with increased mortality,⁹ thrombosis,^10-12 stroke^8,12,13 and renal morbidity.^9,10
• Dosing strategies of rFVIIa for cardiac surgical bleeding remain inconsistent. Older reports analyzed doses of 90 mcg/kg of rFVIIa based on recommendations for patients with hemophilia, while more recent reports have shown efficacy with lower doses ranging from as low as 12 mcg/kg14 to 40 - 50 mcg/kg.^5,6,15-17

PURPOSE
To determine the effects and safety of vld-rFVIIa administration (median 13.33 mcg/kg) in patients who received vld-rFVIIa for cardiac surgical bleeding compared to matched control groups who sustained cardiac surgical bleeding and did not receive vld-rFVIIa

METHODS
(View Poster)

RESULTS
(View Poster)
• 736 patients were included in this study. vld-rFVIIa was administered to 368 patients with a median dose of 13.33 mcg/kg, per patient. Patients who received vld-rFVIIa were matched with 368 patients who met criteria for cardiac surgical bleeding but did not receive vld-rFVIIa therapy.
• Between matched cohorts there were no differences in age, race, Society of Thoracic Surgery morbidity or mortality risk score, preoperative INR, preoperative ejection fraction, diabetes, end-stage renal disease (ESRD) and emergent or urgent surgeries

CONCLUSIONS
Factor 7 for cardiac surgical bleeding does not increase mortality (p=0.075) but is associated with increased blood transfusions
(p<0.0001) and renal failure (p=0.005) in a matched cohort

REFERENCES
1. Hedner U, Bjoern S, Bernvil SS, Tengborn L, Stigendahl L. Clinical experience with human plasma-derived factor VIIa in patients with hemophilia A and high
titer inhibitors. Haemostasis 1989; 19:335-43
2. Andersen ND, Bhattacharya SD, Williams JB, Fosbol EL, Lockhart EL, Patel MB, Gaca JG, Welsby IJ, Hughes GC. Intraoperative use of low-dose
recombinant activated factor VII during thoracic aortic operations. Ann Thorac Surg 2012; 93:1921-8; discussion 1928-9
3. Mayo A, Misgav M, Kluger Y, Geenberg R, Pauzner D, Klausner J, Ben-Tal O. Recombinant activated factor VII (NovoSeven): addition to replacement
therapy in acute, uncontrolled and life-threatening bleeding. Vox Sang 2004; 87:34-40
4. Habib AM, Mousa AY, Al-Halees Z. Recombinant activated factor VII for uncontrolled bleeding postcardiac surgery. J Saudi Heart Assoc 2016; 28:222-31
5. Tritapepe L, De Santis V, Vitale D, Nencini C, Pellegrini F, Landoni G, Toscano F, Miraldi F, Pietropaoli P. Recombinant activated factor VII for refractory
bleeding after acute aortic dissection surgery: a propensity score analysis. Crit Care Med 2007; 35:1685-90
6. Gelsomino S, Lorusso R, Romagnoli S, Bevilacqua S, De Cicco G, Bille G, Stefano P, Gensini GF. Treatment of refractory bleeding after cardiac operations
with low-dose recombinant activated factor VII (NovoSeven): a propensity score analysis. Eur J Cardiothorac Surg 2008; 33:64-71
7. Romagnoli S, Bevilacqua S, Gelsomino S, Pradella S, Ghilli L, Rostagno C, Gensini GF, Sorbara C. Small-dose recombinant activated factor VII (NovoSeven)
in cardiac surgery. Anesth Analg 2006; 102:1320-6
8. Gill R, Herbertson M, Vuylsteke A, Olsen PS, von Heymann C, Mythen M, Sellke F, Booth F, Schmidt TA. Safety and efficacy of recombinant activated factor
VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery. Circulation 2009; 120:21-7
9. Alfirevic A, Duncan A, You J, Lober C, Soltesz E. Recombinant factor VII is associated with worse survival in complex cardiac surgical patients. Ann Thorac
Surg 2014; 98:618-24
10. Bowman LJ, Uber WE, Stroud MR, Christiansen LR, Lazarchick J, Crumbley AJ, 3rd, Kratz JM, Toole JM, Crawford FA, Jr., Ikonomidis JS. Use of
recombinant activated factor VII concentrate to control postoperative hemorrhage in complex cardiovascular surgery. Ann Thorac Surg 2008; 85:1669-76;
discussion 1676-7
11. O'Connell KA, Wood JJ, Wise RP, Lozier JN, Braun MM. Thromboembolic adverse events after use of recombinant human coagulation factor VIIa. JAMA
2006;295:293-8
12. Ponschab M, Landoni G, Biondi-Zoccai G, Bignami E, Frati E, Nicolotti D, Monaco F, Pappalardo F, Zangrillo A. Recombinant activated factor VII increases
stroke in cardiac surgery: a meta-analysis. J Cardiothorac Vasc Anesth 2011; 25:804-10
13. Zangrillo A, Mizzi A, Biondi-Zoccai G, Bignami E, Calabro MG, Pappalardo F, Dedola E, Tritapepe L, Marino G, Landoni G. Recombinant activated factor
VII in cardiac surgery: a meta-analysis. J Cardiothorac Vasc Anesth 2009; 23:34-40
14. Brase J, Finger B, He J, Wirtz K, Stun L, McMillen R, Flynn B. Analysis of Outcomes Using Low-Dose and Early Administration of Recombinant Activated
Factor VII in Cardiac Surgery. Ann Thorac Surg 2016; 102:35-40
15. Habib AM. Comparison of low- and high-dose recombinant activated factor VII for postcardiac surgical bleeding. Indian J Crit Care Med 2016; 20:497-503
16. van de Garde EM, Bras LJ, Heijmen RH, Knibbe CA, van Dongen EP, Wiltink EH, Biesma DH. Low-dose recombinant factor VIIa in the management of
uncontrolled postoperative hemorrhage in cardiac surgery patients. J Cardiothorac Vasc Anesth 2006; 20:573-5
17. Baral P, Cotter E, Gao G, He J, Wirtz K, Sharma A, Zorn Iii T, Muehlebach G, Flynn B. Characteristics Associated With Mortality in 372 Patients Receiving
Low-Dose Recombinant Factor VIIa (rFVIIa) for Cardiac Surgical Bleeding. J Cardiothorac Vasc Anesth 2019