Prospective, Randomised Trial of Two Doses of rFVIIa (NovoSeven) in Haemophilia Patients with Inhibitors Undergoing Surgery

Amy D. Shapiro; Gerald S. Gilchrist; W. Keith Hoots; Herbert A. Cooper; Dennis A. Gastineau

doi:10.1055/s-0037-1615357

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1998; 80(05): 773-778
DOI: 10.1055/s-0037-1615357

Review Article

Schattauer GmbH

Prospective, Randomised Trial of Two Doses of rFVIIa (NovoSeven) in Haemophilia Patients with Inhibitors Undergoing Surgery

Autoren

Amy D. Shapiro

¹From the Indiana University Medical Center, Hemophilia Center, IN, USA
Gerald S. Gilchrist

²From the Department of Pediatrics, Mayo Clinic, Hemophilia Center, MN, USA
W. Keith Hoots

³From the Department of Pediatrics and Internal Medicine, UT-Houston Medical School, TX, USA
Herbert A. Cooper

⁴From the Division of Pediatric Hematology/Oncology, UNC Hospital at Chapel Hill, NC, USA
Dennis A. Gastineau

⁵From the Division of Hematology, Department of Medicine, Mayo Clinic, Hemophilia Center, MN, USA

Abstract

Summary

Recombinant factor VIIa (rFVIIa; NovoSeven^® ; Novo Nordisk) has proven efficacy in the treatment of haemophilic patients with inhibitors. This prospective, double-blind study compared rFVIIa (35 vs. 90 μg/kg) in the initiation and maintenance of haemostasis during and after elective surgery. Patients with inhibitors (FVIII, n = 26; FIX, n = 3) received rFVIIa immediately prior to incision; intraoperatively as needed; every 2 h for the first 48 h; and every 2-6 h for the following 3 days. Haemostasis was evaluated during surgery, at 0, 8, 24 and 48 h and 3, 4 and 5 days after wound closure. After day 5, open-label rFVIIa (90 μg/kg) was available for maintenance. Intraoperative haemostasis was achieved in 28/29 patients. All high-dose patients and 12/15 low dose patients had satisfactory haemostasis during the first 48 h. Twenty-three patients (13/14 high dose) successfully completed the study. Although the 35 μg/kg dose is probably sub-optimal for post-operative management, at least in major procedures, rFVIIa 90 μg/kg is an effective first-line option in surgery for patients with inhibitors.

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Referenzen

References
1 Macik BG. Treatment of factor VIII inhibitors: products and strategies. Semen Thromb Hemost 1993; 19: 13-24.
2 Nilsson IM, Berntop E, Freiburghaus C. Treatment of patients with Factor VIII and IX inhibitors. Thromb Haemost 1993; 70: 56-9.
3 Bray G, Gomperts ED, Courter S, Gruppo R, Gordon EM, Manco-Johnson M, Shapiro A, Scheibel E, White G III, Lee M. A multicenter study of recombinant factor VIII (Recombinate): safety, efficacy and inhibitor risk in previously untreated patients with haemophilia A. The Recombinate Study Group. Blood 1994; 83: 2428-35.
4 Brettler DB, Forsberg MS, Levine PH, Aledort LM, Hiltgartner MW, Kasper CK, Lusher JM, McMillan C, Roberts H. on behalf of the Cooperating Investigators. The use of porcine factor VIII concentrate (Hyate:C) in the treatment of patients with inhibitor antibodies to factor VIII. A multicenter US experience. Arch Intern Med 1989; 149: 1381-5.
5 Hay CRM, Lozier JN, Lee CA, Tradati H, Santagostino E, Ciavarella N, Schiavoni M, Fukiu H, Yoskioka A. Porcine factor VIII in patients with congenital hemophilia and inhibitors: efficacy, patient selection and side effects. Semin Hematol 1994; 31: 20-5.
6 Lusher JM. Use of prothrombin complex concentrates in management of bleeding in hemophiliacs with inhibitors – benefits and limitations. Semin Hematol 1994; 31: 49-52.
7 Rao LVM, Rapaport SI. Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of coagulation. Proc Natl Acad Sci USA 1988; 85: 6687-91.
8 Brinkhous KM, Hedner U, Garris JB, Diness V, Read MS. Effect of recombinant factor VIIa on the hemostatic defect in dogs with hemophilia A, hemophilia B, and von Willebrand disease. Proc Natl Acad Sci USA 1989; 86: 1382-6.
9 Lindley CM, Sawyer WT, Macik BG, Lusher J, Harrison JF, Baird-Cox K, Birch K, Glazer S, Roberts HR. Pharmacokinetics and pharmacodynamics of recombinant factor VIIa. Clin Pharmacol Ther 1994; 55: 638-48.
10 Hedner U, Glazer S. Management of hemophilia patients with inhibitors. Hematol Oncol Clin North Am 1992; 6: 1035-46.
11 Roberts H. Clinical experience with recombinant factor VIIa (Novo Seven^® ): summary of efficacy and safety. Haemophilia 1996; 2: 63.
12 Lusher JM. Recombinant factor VIIa (NovoSeven^® ) in the treatment of internal bleeding in patients with factor VIII and IX inhibitors. Haemostasis 1996; 26: 124-30.
13 Rice KM, Savidge GF. NovoSeven^® (Recombinant factor VIIa) in central nervous system bleeds. Haemost 1996; 26: 131-4.
14 Mølskov Bech R. Recombinant factor VIIa in joint and muscle bleeding episodes. Haemostasis 1996; 26: 135-8.
15 Nicolaisen EM, Hansen LL, Poulsen F, Glazer S, Hedner U. Immunological aspects of recombinant factor VIIa (rFVIIa) in clinical use. Thromb Haemost 1996; 76: 200-4.
16 Hedner U, Glazer S, Pingel K, Alberts KA, Blomback M, Schulman S, Johnsson H. Successful use of recombinant factor VIIa in patients with severe haemophilia A during synovectomy. Lancet 1988; ii: 1193.
17 Ingerslev J, Freidman D, Gastineau D, Gilchrist G, Johnsson H, Lucas G, McPherson JJ, Preston E, Scheibel E, Shuman M. Major surgery in haemophiliac patients with inhibitors using recombinant factor VIIa. Haemostasis 1996; 26: 118-23.
18 O’Marcaigh AS, Schmalz BJ, Shaughnessy WJ, Gilchrist GS. Successful hemostasis during a major orthopedic operation by using recombinant activated factor VII in a patient with severe hemophilia A and a potent inhibitor. Mayo Clin Proc 1994; 69: 641-4.
19 Schulman S, Bech Jensen M, Varon D, Keller N, Gitel S, Horoszowski H, Heim M, Martinowitz U. Feasibility of using recombinant factor VIIa in continuous infusion. Thromb Haemost 1996; 75: 432-6.
20 Egan EL, Bowie EJW, Kazmier FJ, Gilchrist GS, Woods JW, Owen Jr. CA. Effect of surgical operations on certain tests used to diagnose intravascular coagulation and fibrinolysis. Mayo Clin Proc 1974; 49: 658-64.
21 Gaffney PJ, Creighton LJ, Callus M, Thorpe R. Monoclonal antibodies to crosslinked fibrin degradation products (XL-FDP). II. Evaluation in a variety of clinical conditions. Br J Haematol 1988; 68: 91-6.
22 Van Wersch JW, de Vries-Hanje JC, Oosterbos C. Coagulation activation and reactive fibrinolysis in patients receiving oral anticoagulation after total hip or knee replacement. Blood Coag Fibrinol 1994; 5: 604-8.
23 Schmidt ML, Gamerman S, Smith HE, Scott JP, DiMichele DM. Recombinant activated factor VII (rFVIIa) therapy for intracranial hemorrhage in hemophilia A patients with inhibitors. Am J Hematol 1994; 47: 36-40.
24 Glazer S, Hedner U, Falch JF. Clinical update on the use of recombinant factor VIIa. Proceedings of the 2nd International Symposium on inhibitors to coagulation factors. Aledort LM, White GC. eds. New York:: Plenum Publishing Corp; 1993: 163-74.
25 Bell BA, Birch K, Glazer S. Experience with recombinant factor VIIa in an infant hemophilia with inhibitors to FVII:C undergoing emergency central line placement. Am J Pediatr Hematol Oncol 1993; 15: 77-9.