Blood Reviews
Volume 22 , Pages S1-S11 , February 2008

From Theory to Practice: Applying Current Clinical Knowledge and Treatment Strategies to the Care of Hemophilia A Patients With Inhibitors

  • Edward D. Gomperts, MD

      Affiliations

    • Children's Hospital Los Angeles, Division of Hematology/Oncology, 4650 Sunset Blvd., M/S #54, Los Angeles, California 90027, USA
    • Corresponding Author InformationCorresponding author. Tel.: 323-644-8794
  • ,
  • Jan Astermark, MD, PhD

      Affiliations

    • University Hospital Malmö, Department for Hematology and Coagulation Disorders, Malmö, Sweden SE-205 02
  • ,
  • Alessandro Gringeri, MD

      Affiliations

    • Department of Medicine and Medical Specialities, University of Milan and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Via Pace 9, Milan, Italy 20122
  • ,
  • Jerome Teitel, MD

      Affiliations

    • St Michael's Hospital, 30 Bond Street, Room 2-065 Queen, Toronto, Ontario, Canada M5B1W8

References 

  1. Brackmann HH , Wallny T . Immune tolerance: high-dose regimen . In:  Rodriguez-Merchan EC ,  Lee CA editor. Inhibitors in Patients With Hemophilia . Oxford, England: Blackwell Science, Ltd.; 2002;p. 45–48
  2. Hay CR . Factor VIII inhibitors in mild and moderateseverity haemophilia A . Haemophilia . 1998;4(4):558–563
  3. Kasper CK. Diagnosis and Management of Inhibitors to Factors VIII and IX. An Introductory Discussion for Physicians. Vol No. 34. Montréal, Québec: World Federation of Hemophilia; 2004.
  4. Leissinger CA . Prevention of bleeds in hemophilia patients with inhibitors: emerging data and clinical direction . Am J Hematol . 2004;77(2):187–193
  5. Arkin S , Blei F , Fetten J , et al . Human coagulation factor FVIIa (recombinant) in the management of limbthreatening bleeds unresponsive to alternative therapies: results from the NovoSeven emergency-use rogramme in patients with severe haemophilia or with acquired inhibitors . Blood Coagul Fibrinolysis . 2000;11(3):255–259
  6. Astermark J , Donfield SM , DiMichele DM , et al . A randomized comparison of bypassing agents in hemophilia complicated by an inhibitor: the FEIBA NovoSeven Comparative (FENOC) Study . Blood . 2007;109(2):546–551
  7. Hilgartner M , Aledort L , Andes A , Gill J . Efficacy and safety of vapor-heated anti-inhibitor coagulant complex in hemophilia patients. FEIBA Study Group . Transfusion . 1990;30(7):626–630
  8. Key NS , Aledort LM , Beardsley D , et al . Home treatment of mild to moderate bleeding episodes using recombinant factor VIIa (Novoseven) in haemophiliacs with inhibitors . Thromb Haemost . 1998;80(6):912–918
  9. Negrier C, Goudemand J, Sultan Y, Bertrand M, Rothschild C, Lauroua P, et al. Multicenter retrospective study on the utilization of FEIBA in France in patients with factor VIII and factor IX inhibitors . Thromb Haemost . 1997;77(6):1113–1119
  10. Shapiro AD , Gilchrist GS , Hoots WK , Cooper HA , Gastineau DA . Prospective, randomised trial of two doses of rFVIIa (NovoSeven) in haemophilia patients with inhibitors undergoing surgery . Thromb Haemost . 1998;80(5):773–778
  11. Tjønnfjord GE . Activated prothrombin complex concentrate (FEIBA) treatment during surgery in patients with inhibitors to FVIII/IX: the updated Norwegian experience . Haemophilia . 2004;10(suppl 2):41–45
  12. Ho AY , Height SE , Smith MP . Immune tolerance therapy for haemophilia . Drugs . 2000;60(3):547–554
  13. DiMichele D , Rivard G , Hay C , Antunes S . Inhibitorsin haemophilia: clinical aspects . Haemophilia . 2004;10(suppl 4):140–145
  14. Teitel J , Berntorp E , Collins P , et al . A systematic approach to controlling problem bleeds in patients with severe congenital haemophilia A and high-titre inhibitors . Haemophilia . 2007;13:256–263
  15. Parameswaran R , Shapiro AD , Gill JC , Kessler CM . Dose effect and efficacy of rFVIIa in the treatment of haemophilia patients with inhibitors: analysis from the Hemophilia and Thrombosis Research Society Registry . Haemophilia . 2005;11(2):100–106
  16. Gomperts ED, Astermark J, Gringeri A, Teitel JM. From theory to practice: applying current critical knowledge and treatment strategies to the care of inhibitor patients. Presented at: XXIst Congress of the International Society on Thrombosis and Haemostasis; July 11, 2007; Geneva, Switzerland.
  17. Todd KH , Funk KG , Funk JP , Bonacci R . Clinical significance of reported changes in pain severity . Ann Emerg Med . 1996;27(4):485–489
  18. Hayashi T , Tanaka I , Shima M , et al . Unresponsiveness to factor VIII inhibitor bypassing agents during haemostatic treatment for life-threatening massive bleeding in a patient with haemophilia A and a high responding inhibitor . Haemophilia . 2004;10(4):397–400
  19. Klinge J , Auberger K , Auerswald G , Brackmann HH , Mauz-Korholz C , Kreuz W . Prevalence and outcome of intracranial haemorrhage in haemophiliacs — a survey of the paediatric group of the German Society of Thrombosis and Haemostasis (GTH) . Eur J Pediatr . 1999;158(suppl 3):S162–S165
  20. Stieltjes N , Calvez T , Demiguel V , et al.   Intracranialhaemorrhages in French haemophilia patients (1991—2001): clinical presentation, management and prognosis factors for death . Haemophilia . 2005;11(5):452–458
  21. Nelson MD , Maeder MA , Usner D , et al. , Hemophilia Growth and Development Study    Prevalence and incidence of intracranial haemorrhage in a population of children with haemophilia . Haemophilia . 1999;5(5):306–312
  22. Kulkarni R , Ponder KP , James AH , et al . Unresolved issues in diagnosis and management of inherited bleeding disorders in the perinatal period: a White Paper of the Perinatal Task Force of the Medical and Scientific Advisory Council of the National Hemophilia Foundation, USA . Haemophilia . 2006;12(3):205–211
  23. Nuss R , Soucie JM , Evatt B . Changes in the occurrence of and risk factors for hemophilia-associated intracranial hemorrhage . Am J Hematol . 2001;68(1):37–42
  24. Balkan C , Kavakli K , Karapinar D . Iliopsoas haemorrhage in patients with haemophilia: results from one centre . Haemophilia . 2005;11(5):463–467
  25. Rodriguez-Merchan EC . Pathogenesis of musculoskeletal complications of haemophilia . In:  Rodriguez-Merchan EC ,  Lee CA editor. Inhibitors in Patients With Hemophilia . Oxford, England: Blackwell Science, Ltd.; 2002;p. 115–119
  26. Valentino LA , Martinowitz U , Doolas A , Murali P . Surgical excision of a giant pelvic pseudotumour in a patient with haemophilia A . Haemophilia . 2006;12(5):541–544
  27. FEIBA VH . [package insert] . Westlake Village, CA: Baxter Healthcare Corporation; April 2005;
  28. NovoSeven Coagulation Factor VIIa R. [package insert] . Princeton, NJ: Novo Nordisk Inc.; October 2006;
  29. NovoSeven. European Medicines Agency (EMEA). EPARs for authorised medicinal products for human use. Annex I — Summary of product characteristics. http://www.emea.europa.eu/humandocs/Humans/EPAR/novoseven/novoseven.htm. Updated March 9, 2007. Accessed October 8, 2007.
  30. Schneiderman J , Nugent DJ , Young G . Sequential therapy with activated prothrombin complex concentrate and recombinant factor VIIa in patients with severe haemophilia and inhibitors . Haemophilia . 2004;10(4):347–351
  31. Schneiderman J , Rubin E , Nugent DJ , Young G . Sequential therapy with activated prothrombin complex concentrates and recombinant FVIIa in patients with severe haemophilia and inhibitors: update of our previous experience . Haemophilia . 2007;13(3):244–248
  32. Aledort LM . Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity . JThrombHaemost . 2004;2(10):1700–1708
  33. Rivard GE , St Louis J , Lacroix S , Champagne M , Rock G . Immunoadsorption for coagulation factor inhibitors: a retrospective critical appraisal of 10 consecutive cases from a single institution . Haemophilia . 2003;9(6):711–716
  34. Bloom AL . Current status and trends in the treatment of hemophilic patients with inhibitors . Prog Clin Biol Res . 1981;72:123–138
  35. Antunes SV , Vicari P , Cavalheiro S , Bordin JO . Intracranial haemorrhage among a population of haemophilic patients in Brazil . Haemophilia . 2003;9(5):573–577
  36. Luchtman-Jones L , Valentino LA , Manno C . Considerations in the evaluation of haemophilia patients for short-term prophylactic therapy: a paediatric and adult case study . Haemophilia . 2006;12(1):82–86
  37. Turecek PL , Varadi K , Keil B , et al . Factor VIII inhibitor-bypassing agents act by inducing thrombin generation and can be monitored by a thrombin generation assay . Pathophysiol Haemost Thromb . 2003;33(1):16–22
  38. Varadi K , Schoppmann A , Turecek P . Mode of Action of FEIBA: Applying a Cell Based Model of Hemostasis. Baxter Scientific Series Vol No. 5 . Westlake Village, Calif: Baxter Healthcare Corp; 2006;
  39. Hoffman M , Monroe DM , Roberts HR . Activated factor VII activates factors IX and X on the surface of activated platelets: thoughts on the mechanism of action of high-dose activated factor VII . Blood Coagul Fibrinolysis . 1998;9(suppl 1):S61–S65
  40. Brackmann HH , Gormsen J . Massive factor-VIII infusion in haemophiliac with factor-VIII inhibitor, high responder [letter] . Lancet . 1977;2(8044):933
  41. DiMichele D , Negrier C . A retrospective postlicensure survey of FEIBA efficacy and safety . Haemophilia . 2006;12(4):352–362
  42. Hilgartner MW , Makipernaa A , DiMichele DM . Long-term FEIBA prophylaxis does not prevent progression of existing joint disease . Haemophilia . 2003;9(3):261–268
  43. Leissinger CA , Becton DL , Ewing NP , Valentino LA . Prophylactic treatment with activated prothrombin complex concentrate (FEIBA) reduces the frequency of bleeding episodes in paediatric patients with haemophilia A and inhibitors . Haemophilia . 2007;13(3):249–255
  44. Lindley CM , Sawyer WT , Macik BG , et al . Pharmacokinetics and pharmacodynamics of recombinant factor VIIa . Clin Pharmacol Ther . 1994;55(6):638–648
  45. Villar A , Aronis S , Morfini M , et al . Pharmacokinetics of activated recombinant coagulation factor VII (NovoSeven) in children vs. adults with haemophilia A . Haemophilia . 2004;10(4):352–359
  46. Varadi K , Negrier C , Berntorp E , et al . Monitoring the bioavailability of FEIBA with a thrombin generation assay . JThrombHaemost . 2003;1(11):2374–2380
  47. Konkle BA , Ebbesen LS , Erhardtsen E , et al . Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors . JThrombHaemost . 2007;5(9):1904–1913
  48. Morfini M , Auerswald G , Kobelt RA , et al . Prophylactic treatment of haemophilia patients with inhibitors: clinical experience with recombinant factor VIIa in European Haemophilia Centres . Haemophilia . 2007;13(5):502–507
  49. Allen G , Aledort L . Therapeutic decision-making in inhibitor patients . Am J Hematol . 2006;81(1):71–72
  50. Key NS , Christie B , Henderson N , Nelsestuen GL . Possible synergy between recombinant factor VIIa and prothrombin complex concentrate in hemophilia therapy . Thromb Haemost . 2002;88(1):60–65
  51. PRO-FEIBA. A prospective, randomized, cross-over study of an activated prothrombin complex concentrate for secondary prophylaxis in patients with hemophilia A and inhibitors. ClinicalTrials.gov Web site. http://www.clinicaltrial.gov/ct/show/NCT00221195?order=6. Verified September 2005. Accessed August 2, 2006.

PII: S0268-960X(08)70001-8

doi: 10.1016/S0268-960X(08)70001-8

Blood Reviews
Volume 22 , Pages S1-S11 , February 2008