A Healthy Hemophilic Patient without Arthropathy: From Concept to Clinical Reality

Erik Berntorp; Jan J. Michiels

doi:10.1055/s-2003-37934

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2003; 29(1): 005-010
DOI: 10.1055/s-2003-37934

A Healthy Hemophilic Patient without Arthropathy: From Concept to Clinical Reality

Erik Berntorp¹ , Jan J. Michiels²

¹Professor, Department of Coagulation Disorders, Lund University, Malmö University Hospital, Malmö, Sweden
²Goodheart Institute and Foundation, Haemostasis and Thrombosis Science Center, Rotterdam, The Netherlands, and Hemostasis Thrombosis Research, Department of Hematology, University Hospital, Antwerp, Belgium

Abstract

ABSTRACT

Hemophilia is characterized by joint hemorrhage with subsequent development of arthropathy. During the past 40 to 50 years, factor VIII concentrates have been developed that enable effective treatment of bleeding. However, the development of dosing, including the implementation of prophylaxis, has been hampered by concentrate transmission of blood-borne diseases. Since the advent of viral reducing procedures that were applied to plasma-derived products and the implementation of recombinant DNA technology into the manufacturing procedure, concentrates can be considered as safe today, and hemophilic care can be more focused on the treatment modalities as such. Thus, prophylaxis is being improved and made available to more patients. Studies are in progress in order to give more scientific evidence behind its use. Magnetic resonance imaging (MRI) seems promising in scaling early arthropathy and may be a tool in the future, superior to plain X-ray and orthopedic examination, to follow patients on prophylaxis, especially children. The development of inhibitors is the most severe threat to the health of hemophiliacs today and in the future. Much has been done to elucidate genetic factors predisposing for inhibitors, and the reactivity of inhibitors with the factor VIII molecule has also been investigated. More has to be done, however, and there are still many open issues regarding immune tolerance treatment and treatment of acute bleeding in inhibitor patients. Hemophilic care has come far in order to restore health for the hemophilic population. The treatment is effective in the prevention of joint disease and the inhibitor problem is handled better now. Side effects have been reduced to a minimum. In addition, carrier and prenatal diagnosis add important contributions to improve life for the patient and his family. The next important step for the future is gene therapy, and early clinical studies are already in progress.

KEYWORD

Hemophilia - factor VIII - prophylaxis - inhibitor - gene therapy

Volltext

Referenzen

REFERENCES

1 Pavlovsky A. Contribution to the pathogenesis of haemophilia. Blood . 1947; 2 185-191
2 Biggs R, Douglas A S, Macfarlane R G. et al . Christmas disease: a condition previously mistaken for haemophilia. BMJ . 1952; 2 1378-1382
3 Ahlberg Å. Haemophilia in Sweden. VII. Incidence, treatment and prophylaxis of arthropathy and other musculoskeletal manifestations of haemophilia A and B. Acta Orthop Scand . 1965; (Suppl 77) 7-80
4 White G C, Rosendaal F, Aledort L M. et al . Definitions in haemophilia. Thromb Haemost . 2001; 85 560
5 Kemball-Cook G, Tuddenham E GD. The molecular defect in hemophilia A. In: Forbes CD, Aledort L, Madhok R, eds. Hemophilia London: Chapman & Hall 1997: 21-33
6 Roberts H R, Liles D K. The molecular biology of hemophilia B. In: Forbes CD, Aledort L, Madhok R, eds. Hemophilia London: Chapman & Hall 1997: 35-50
7 Ginsburg D. Molecular genetics of hemophilia. In: Hematology 2000 Washington, D.C.: American Society of Hematology 2000: 241-246
8 Rosendaal F R, Smith C, Briet E. Haemophilia treatment in historical perspective: a review of medical and social developments. Ann Hematol . 1991; 62 5-15
9 Nilsson I M. History and demography of hemophilia with special reference to the situation in Sweden. In: Hemophilia Stockholm: Pharmacia Plasma Products 1994: 2-5
10 Triemstra A HM, Smit C, van der Ploeg M H, Briët E, Rosendaal F R. Two decades of haemophilia treatment in the Netherlands, 1972-92. Haemophilia . 1995; 1 165-171
11 Liesner R J, Khair K, Hann I M. The impact of prophylactic treatment on children with severe haemophilia. Br J Haematol . 1996; 92 973-978
12 Nilsson I M, Hedner U, Ahlberg Å. Haemophilia prophylaxis in Sweden. Acta Paediatr Scand . 1976; 65 129-135
13 Berntorp E. Methods of haemophilia care delivery: regular prophylaxis versus episodic treatment. Haemophilia . 1995; 1(Suppl 1) 3-7
14 Nilsson I M, Blombäck M, Ahlberg Å. Our experience in Sweden with prophylaxis on haemophilia. Proceedings of the 5th Congress of the World Federation of Haemophilia, Montreal 1968; Bibl Haematol, No. 34, New York: Karger. 1970: 111-124
15 Pettersson H, Ahlberg Å, Nilsson I M. A radiologic classification of haemophilic arthropathy. Clin Orthop . 1980; 149 153-159
16 Nilsson I M, Berntorp E, Löfqvist T, Pettersson H. Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B. J Intern Med . 1992; 232 25-32
17 Nilsson I M. Replacement therapy. In: Hemophilia Stockholm: Pharmacia Plasma Products 1994: 30-49
18 Pettersson H, Gilbert M. Diagnostic Imaging in Haemophilia: Musculoskeletal and Other Haemorrhagic Complications. Berlin: Springer-Verlag 1985: 56-65
19 Fischer K. Treatment Strategies for Severe Haemophilia. In: Search of the Optimal Treatment Utrecht, The Netherlands: University of Utrecht; 2001. Thesis
20 Aledort L M, Haschenmeyer R H, Pettersson H. A longitudinal study of orthopaedic outcomes for severe factor VIII-deficient haemophiliacs. The Orthopaedic Outcome Study Group. J Intern Med . 1994; 236 391-399
21 Szucs T D, Öffner A, Schramm W. Socioeconomic impact of haemophilia care: results of a pilot study. Haemophilia . 1996; 2 211-217
22 Carlsson M, Björkman S, Berntorp E. Multidose pharmacokinetics of factor IX: implications for dosing in prophylaxis. Haemophilia . 1998; 4 83-88
23 Carlsson M, Berntorp E, Björkman S, Lindvall K. Pharmacokinetic dosing in prophylactic treatment of hemophilia A. Eur J Haematol . 1993; 51 247-252
24 Astermark J, Berntorp E, White G C, Kroner B L, and the MIBS Study Group. The Malmö International Brother Study (MIBS): further support for genetic predisposition to inhibitor development. Haemophilia . 2001; 7 267-271
25 Brackmann J H, Gormsen J. Massive factor VIII infusion in haemophiliacs with factor VIII inhibitor, high responder. Lancet . 1977; 2 933
26 Mauser-Bunschoten E P, Nieuwenhuis H K, Roosendaal G, van den Berg M. Low-dose immune tolerance induction in hemophilia A patients with inhibitors. Blood . 1995; 86 983-988
27 Ewing N P, Sander N L, Dietrich S L, Kasper C K. Induction of immune tolerance to factor VIII in hemophiliacs with inhibitors. JAMA . 1988; 259 65-68
28 Nilsson I M, Berntorp E, Zettervall O. Induction of immune tolerance in patients with hemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide, and factor VIII. N Engl J Med . 1988; 318 947-950
29 Mariani G, Kroner B. International Immune Tolerance Registry, 1997 Update. Vox Sang . 1999; 77(Suppl 1) 25-27
30 DiMichele D M, Kroner B L. Analysis of the North American Immune Tolerance Registry (NAITR) 1993-1997; current practice implications. Vox Sang . 1999; 77(Suppl 1) 31-32
31 Key N S, Aledort L M, Beardsley D. et al . Home treatment of mild and moderate episodes using recombinant factor VIIa (Novoseven) in hemophiliacs with inhibitors. Thromb Haemost . 1998; 80 912-918
32 Négrier C, Goudemand J, Sultan Y. 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 1113-1119
33 Shapiro A D, Gilchrist G S, Hoots W K, Cooper H A, Gastineau D A. Prospective, randomised trial of two doses of rFVIIa (NovoSeven) in patients with inhibitors undergoing surgery. Thromb Haemost . 1998; 80 773-778
34 White G C. Gene therapy in hemophilia: clinical trials update. Thromb Haemost . 2001; 86 172-177