Elective orthopedic surgery for hemophilia patients with inhibitors: New opportunities.

We report a series of 108 elective orthopedic surgical procedures in hemophilia patients with inhibitors, comprising 88 cases in which radiosynoviorthesis was performed and 20 cases in which major orthopedic procedures were carried out. Hemostatic cover was provided by recombinant factor VIIa (rFVIIa, NovoSeven(R), Novo Nordisk, Bagsvaerd, Denmark) in 17 cases, and by FVIII anti-inhibitor product (FEIBA, Baxter Corp, Toronto, Canada) in the remaining three procedures. A total of 51 patients from nine centers worldwide were included. The results of the procedures were characterized as good (82 procedures), fair (15), or poor (11). Postoperative bleeding complications requiring further surgical intervention occurred in three (15%) of the 20 major orthopedic procedures; all three procedures used rFVIIa as a hemostatic agent. Despite these complications, however, our study has shown that rFVIIa allows hemophilic patients with high inhibitor titers to undergo elective orthopedic surgery (EOS) with a greater expectation of success, leading to an improved quality of life. Thorough analysis of each case as part of a multidisciplinary team will help to identify further inhibitor patients in whom EOS can be performed both safely and effectively.

[1]  E. Rodríguez‐Merchán,et al.  The haemophilic joints: new perspectives , 2004 .

[2]  M. Morfini,et al.  A prospective study of recombinant activated factor VII administered by continuous infusion to inhibitor patients undergoing elective major orthopaedic surgery: a pharmacokinetic and efficacy evaluation , 2003, British journal of haematology.

[3]  I. Hvid,et al.  Orthopaedic surgery in haemophilic patients with inhibitors: an overview , 2002, Haemophilia : the official journal of the World Federation of Hemophilia.

[4]  Christine A. Lee,et al.  Inhibitors in Patients with Haemophilia , 2002 .

[5]  J. Ingerslev,et al.  Efficacy and Safety of Recombinant Factor VIIa in the Prophylaxis of Bleeding in Various Surgical Procedures in Hemophilic Patients with Factor VIII and Factor IX Inhibitors , 2000, Seminars in thrombosis and hemostasis.

[6]  Christine A. Lee,et al.  Musculoskeletal Aspects of Haemophilia , 2000 .

[7]  Scharrer,et al.  Incidence of inhibitors in haemophilia A patients – a review of recent studies of recombinant and plasma‐derived factor VIII concentrates , 1999, Haemophilia : the official journal of the World Federation of Hemophilia.

[8]  Penner.  Management of haemophilia in patients with high‐titre inhibitors: focus on the evolution of activated prothrombin complex concentrate AUTOPLEX® T , 1999, Haemophilia : the official journal of the World Federation of Hemophilia.

[9]  Leissinger.  Use of prothrombin complex concentrates and activated prothrombin complex concentrates as prophylactic therapy in haemophilia patients with inhibitors , 1999, Haemophilia : the official journal of the World Federation of Hemophilia.

[10]  A D Shapiro,et al.  Prospective, Randomised Trial of Two Doses of rFVIIa (NovoSeven) in Haemophilia Patients with Inhibitors Undergoing Surgery , 1998, Thrombosis and Haemostasis.

[11]  J. Ingerslev,et al.  Clinical use of recombinant FVIIa (rFVIIa). , 1998, Transfusion science.

[12]  H. Roberts,et al.  Clinical experience with activated factor VII: focus on safety aspects. , 1998, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[13]  M. Morfini,et al.  Experiences with continuous infusion of recombinant activated factor VII. , 1998, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[14]  S. Schulman,et al.  Feasibility of Using Recombinant Factor VIIa in Continuous Infusion , 1996, Thrombosis and Haemostasis.

[15]  J. Oldenburg,et al.  Immune Tolerance for the Treatment of Factor VIII Inhibitors ‐ Twenty Years' ‘Bonn Protocol’ , 1996, Vox sanguinis.

[16]  E. Scheibel,et al.  Major surgery in haemophilic patients with inhibitors using recombinant factor VIIa. , 1996, Haemostasis.

[17]  A. O'marcaigh,et al.  Successful hemostasis during a major orthopedic operation by using recombinant activated factor VII in a patient with severe hemophilia A and a potent inhibitor. , 1994, Mayo Clinic proceedings.

[18]  E. Gordon,et al.  A multicenter study of recombinant factor VIII (recombinate): safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A. The Recombinate Study Group. , 1994, Blood.

[19]  S. Schulman,et al.  Recombinant factor VIIa in multiple surgery. , 1994, Thrombosis and haemostasis.

[20]  S. Arkin,et al.  Recombinant Factor VIII for the Treatment of Previously Untreated Patients with Hemophilia A: Safety, Efficacy, and Development of Inhibitors , 1993 .

[21]  M. Hilgartner,et al.  Frequency of inhibitor development in haemophiliacs treated with low-purity factor VIII , 1993, The Lancet.

[22]  E. Santagostino,et al.  Use of porcine factor VIII for surgical procedures in hemophilia A patients with inhibitors. , 1993, Seminars in hematology.

[23]  U. Hedner,et al.  Recombinant activated factor VII in the treatment of bleeding episodes in patients with inherited and acquired bleeding disorders. , 1993, Transfusion medicine reviews.

[24]  S. Arkin,et al.  Recombinant factor VIII for the treatment of previously untreated patients with hemophilia A. Safety, efficacy, and development of inhibitors. Kogenate Previously Untreated Patient Study Group. , 1993, The New England journal of medicine.

[25]  W. Kreuz,et al.  Incidence of development of factor VIII and factor IX inhibitors in haemophiliacs , 1992, The Lancet.

[26]  M. Hilgartner,et al.  Efficacy and safety of vapor‐heated anti‐inhibitor coagulant complex in hemophilia patients. FEIBA Study Group , 1990, Transfusion.

[27]  D. Brettler,et al.  The use of porcine factor VIII concentrate (Hyate:C) in the treatment of patients with inhibitor antibodies to factor VIII. A multicenter US experience. , 1989, Archives of internal medicine.

[28]  M. Blombäck,et al.  SUCCESSFUL USE OF RECOMBINANT FACTOR VIIa IN PATIENT WITH SEVERE HAEMOPHILIA A DURING SYNOVECTOMY , 1988, The Lancet.

[29]  R. Bona,et al.  Porcine factor VIII and plasmapheresis in the management of hemophiliac patients with inhibitors , 1986, American journal of hematology.

[30]  H. Pettersson,et al.  Diagnostic Imaging in Hemophilia , 1985, Springer London.

[31]  G. White,et al.  Treatment of a high titer anti-factor-VIII antibody by continuous factor VIII administration: report of a case. , 1983, Blood.

[32]  J. McComb,et al.  Use of activated prothrombin complex concentrate over multiple surgical episodes in a hemophilic child with an inhibitor. , 1983, The Journal of pediatrics.

[33]  G. Knatterud,et al.  The use of factor eight inhibitor by-passing activity (FEIBA immuno) product for treatment of bleeding episodes in hemophiliacs with inhibitors. , 1983, Blood.

[34]  C. Abildgaard,et al.  Anti-inhibitor Coagulant Complex (Autoplex) for treatment of factor VIII inhibitors in hemophilia , 1980 .

[35]  B. Hopkin.  Frapper fort ou doucement:A Gramnegative dilemma. , 1978 .