Surgical evaluation of a recombinant factor VIII prepared using a plasma/albumin-free method: Efficacy and safety of Advate in previously treated patients

Claude Négrier; Amy Shapiro; Erik Berntorp; Ingrid Pabinger; Michael Tarantino; Antonio Retzios; Phillip Schroth; Bruce Ewenstein

doi:10.1160/TH08-02-0117

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(02): 217-223
DOI: 10.1160/TH08-02-0117

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Surgical evaluation of a recombinant factor VIII prepared using a plasma/albumin-free method: Efficacy and safety of Advate in previously treated patients

Claude Négrier

¹Hôpital Edouard Herriot, Lyon, France

,

Amy Shapiro

²Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, USA

,

Erik Berntorp

³University Hospital MAS, Malmö, Sweden

,

Ingrid Pabinger

⁴Allgemeines Krankenhaus der Stadt Wien, Vienna, Austria

,

Michael Tarantino

⁵Comprehensive Bleeding Disorders Center, Peoria, Illinois, USA

,

Antonio Retzios

⁶Baxter Healthcare Corporation, Westlake Village, California, USA

,

Phillip Schroth

⁶Baxter Healthcare Corporation, Westlake Village, California, USA

,

Bruce Ewenstein

⁶Baxter Healthcare Corporation, Westlake Village, California, USA

› Author Affiliations

Abstract

Summary

Evaluation of factor F(V)III replacement in patients with haemophilia A undergoing surgery is critical for FVIII concentrates, yet large scale, multi-center prospective studies, particularly using continuous infusion, are generally lacking for new products. This study evaluated efficacy and safety of a newly developed recombinant FVIII (rAHF-PFM) administered by bolus or continuous infusion in haemophilia A patients undergoing surgery. Subjects ≥5 years of age with baseline FVIII:C ≤2%, and ≥150 prior FVIII exposure days were included in this prospective, international, open-label, uncontrolled clinical trial. rAHFPFM was administered perioperatively by bolus infusion (BI) or continuous infusion (CI) according to the standard use at the center to prevent bleeding complication. Both the surgeon and haematologist rated efficacy during hospitalization. Fifty-eight subjects underwent 65 surgical procedures (22 major haemor rhagic risk; 35 minor, 8 dental procedures). Bolus infusion was used exclusively in 47 procedures and continuous infusion, with or without supplemental bolus infusions, in 18.Haemostatic efficacy was assessed as excellent or good for 100% of intraoperative ratings (17 CI, 44 BI, 61 total procedures), and 100% of postoperative ratings performed at time of discharge (18 CI, 44 BI, 62 total procedures). Median total consumption of rAHF-PFM during hospitalization was 822 IU/kg/surgery with CI and 910 IU/kg/surgery with BI. Overall rAHF-PFM was well tolerated, and FVIII inhibitors were not detected. In conclusion, rAHF-PFM administered via continuous infusion or bolus injections is safe, non-immunogenic, and effective for perioperative hemostatic management in previously treated haemophilia A patients.

Keywords

Haemophilia A - factor VIII - rAHF-PFM - rFVIII - surgery - continuous infusion

Full Text

References

References
1 Martinowitz U, Schulman S. Continuous infusion of coagulation products. Int J Pediatr Hematol Oncol 1994; 01: 471-478.
2 Batorova A, Martinowitz U. Continuous infusion of coagulation factors. Haemophilia 2002; 08: 170-177.
3 Schulman S. Continuous infusion. Haemophilia 2003; 09: 368-375.
4 Ewenstein BM, Collins P, Tarantino MD. et al. Hemophilia therapy innovation: Development of an advanced category recombinate factor VIII by a plasma/ albumin-free method. Semin Hematol 2004; 41 (1 Suppl 2) 1-18.
5 Tarantino MD, Collins PW, Hay PW. et al. Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Haemophilia 2004; 10: 428-437.
6 Fernandez M, Yu T, Bjornson E. et al. Stability of ADVATE, Antihemophilic Factor (Recombinant) Plasma/Albumin-Free Method, during simulated continuous infusion. Blood Coagul Fibrinolysis 2006; 17: 165-171.
7 Verbruggen B, Novakova I, Wessels H. et al. The Nijmegen modification of the Bethesda assay for Factor VIII: C inhibitors: Improved specificity and reliability. Thromb Haemost 1995; 73: 247-251.
8 Bona RD, Weinstein RA, Weisman SJ. et al. The use of continuous infusion of factor concentrates in the treatment of hemophilia. Am J Hematol 1989; 32: 8-13.
9 Campbell PJ, Rickard KA. Continuous and intermittent infusion of coagulation factor concentrates in patients undergoing surgery: a single centre Australian experience. Aust N Z J Med 1998; 28: 440-445.
10 Dingli D, Gastineau DA, Gilchrist GS. et al. Continuous factor VIII infusion therapy in patients with haemophilia A undergoing surgical procedures with plasma-derived or recombinant factor VIII concentrates. Haemophilia 2002; 08: 629-634.
11 Hathaway WE, Christian MJ, Clarke SL. et al. Comparison of continuous and intermittent Factor VIII concentrate therapy in hemophilia A. Am J Hematol 1984; 17: 85-88.
12 Hay CRM, Doughty HI, Savidge GF. Continuous infusion of factor VIII for surgery and major bleeding. Blood Coagul Fibrinolysis 2001; 07 (Suppl. 01) S15-S19.
13 Koestenberger M, Raith W, Muntean W. High titre inhibitor after continuous factor VIII administration for surgery in a young infant. Haemophilia 2000; 06: 120.
14 Martinowitz U, Schulman S, Gitel S. et al. Adjusted dose continuous infusion of factor VIII in patients with haemophilia A. Br J Haematol 1992; 82: 729-734.
15 Negrier C, Menart C, Attali O. et al. Evaluation of coagulation equilibrium at baseline and during factor VIII and factor IX replacement in haemophiliacs. Blood Coagul Fibrinolysis 1998; 09 (Suppl. 01) S135-S141.
16 Rochat C, McFadyen ML, Schwyzer R. et al. Continuous infusion of intermediatepurity factor VIII in haemophilia A patients undergoing elective surgery. Haemophilia 1999; 05: 181-186.
17 Sennett MM, de Alarcon PA. Successful use of Re-Facto continuous infusion in two paediatric patients with severe haemophilia A undergoing orthopaedic surgery. Haemophilia 2004; 10: 655-660.
18 Stieltjes N, Altisent C, Auerswald G. et al. Continuous infusion of B-domain deleted recombinant factor VII (ReFacto) in patients with haemophilia A undergoing surgery: clinical experience. Haemophilia 2004; 10: 452-458.
19 Suzuki T, Arai M, Miyasaka S. et al. Factor VIII inhibitor developed in a 60-year-old patient with mild hemophilia A after surgery for colon cancer. Int J Hematol 1995; 62: 127-132.
20 Tagariello G, Davoli PG, Gajo GB. et al. Safety and efficacy of high-purity concentrates in haemophiliac undergoing surgery by continuous infusion. Haemophilia 1999; 05: 426-430.
21 Baglin T, Beacham E. Is a change of factor VIII product a risk factor for the development of a factor VIII inhibitor?. Thromb Haemost 1998; 80: 1036-1037.
22 Liu ML, Nakaya S, Thompson AR. Non-inversion factor VII mutations in 80 hemophilia including 24 with alloimmune responses. Thromb Haemost 2002; 87: 273-276.
23 Robbins D, Kulkarni R, Gera R. et al. Successful treatment of high titer inhibitors in mild hemophilia A with avoidance of factor VIII and immunosuppressive Therapy. Am J Hematol 2001; 68: 184-188.
24 Sharathkumar A, Lillicrap D, Blanchette VS. et al. Intensive exposure to factor VIII is a risk factor for inhibitor development in mild hemophilia A. J Thromb Haemost 2003; 01: 1228-1236.
25 van den Brink EN, Timmermans SM, Turenhout EA. et al. Longitudinal analysis of factor VIII inhibitors in an previously untreated mild haemophilia A patient with an Arg 593-Cys substitution. Thromb Haemost 1999; 81: 723-726.
26 White B, Cotter M, Byrne M. et al. High responding factor VIII inhibitors in mild haemophilia – is there a link with recent changes in clinical practice?. Haemophilia 2000; 06: 113-115.
27 von Auer C, Oldenburg J, von Depka M. et al. Inhibitor development in patients with hemophilia A after continuous infusion of FVIII concentrates. Ann NY Acad Sci 2005; 1051: 498-505.
28 Gouw SC, van den Berg HM, van den Berg HM. for the CANAL Study Group. Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study. Blood 2007; 109: 4648-4654.
29 Gouw SC, van den Berg HM, le Cessie S. et al. Treatment characteristics and the risk of inhibitor development: A multi-center cohort study among previously untreated patients with severe hemophilia A. J Thromb Haemost 2007; 05: 1383-1390.
30 Mulcahy R, Walsh M, Scully MF. Retrospective audit of a continuous infusion protocol for haemophilia A at a single haemophilia treatment center. Haemophilia 2005; 11: 208-215.
31 Wight J, Paisley S. The epidemiology of inhibitors in haemophilia A: a systematic review. Haemophilia 2003; 09: 418-435.
32 Ragni MV, Miller BJ, Whalen R. et al. Bleeding tendency, platelet function, and pharmacokinetics of ibuprofen and zidovudine in HIV(+) hemophilic men. Am J Hematol 1992; 40: 176-182.
33 Schwarz HP, Lenting PJ, Binder B. et al. Involvement of low-density lipoprotein receptor-related protein (LRP) in the clearance of factor VIII in von Willebrand factor- deficient mice. Blood 2000; 95: 1703-1708.
34 Warren JS, Ward PA. The inflammatory response. In: Lichtman M, Beutler E, Kipps TJ, Williams WJ. Williams Manual of Hematology. 6th ed.. McGraw-Hill Medical Publishing Division; 2001: 67-76.
35 Bidlingmaier C, Deml MM, Kurnik K. Continuous infusion of factor concentrates in children with haemophilia A in comparision with bolus injection. Haemophilia 2006; 12: 212-217.
36 Lee M, Morfini M, Negrier C. et al. The pharmacokinetics of coagulation factors. Haemophilia 2006; 12 (Suppl. 03) 1-7.