Instructions

Take Another Course

Post-Test

Abstract:

In general practice, in order to avoid arthropathy later in life it is recommended that all children begin prophylactic treatment before joint damage has occurred. This therapy is relatively expensive, and having to inject young children on a regular basis is, at best, a burden. In the interest of providing information on alternate starting points for prophylaxis based on the individual patient, the effects of long-term arthropathy was studied. For this study, 76 patients born between 1965 and 1985 were included that had demonstrated severe hemophilia. Details on this group are seen in Table 1 below. Arthropathy was measured using the Petterson score, with this group showing that the longer prophylaxis was initially postponed, the higher the score later in life—marking a direct correlation between the postponement of prophylaxis and arthropathic severity. In fact, note the researchers, children who start prophylaxis immediately after their first joint bleed show little or no signs of arthropathy later in life.

Prophylaxis, Arthropathy, Pettersson score, venipuncture, (WHO) World Health Organization

Discussion:

This study dealt with patients suffering from severe hemophilia, defined as repeated hemarthroses resulting in severe arthropathy. Prophylactic infusions were first started in Sweden in 1958 to control bleeding. Clotting factor concentrates were used to keep levels above 0.01 IU/mL. Over years of successful therapy with prophylaxis, it is now considered the standard of care for hemophiliacs in order to avoid the long-term effects of joint bleeds, as recognized by both the World Health Organization and the U.S. National Hemophilia Foundation Medical and Scientific Advisory Committee^4,5. Cost and venous access are the principle reasons prophylaxis is under debate, even though it is understood that the earlier prophylaxis is begun, the higher the quality of life (lower degree of arthropathy). This is why the start age for prophylaxis is still being considered. Some centers, note the researchers, start prophylaxis before the first joint bleed has occurred at about one year of age, while others advocate waiting until after the first joint bleed to begin therapy^7-9.

Throughout the years of prophylaxis’ use, there have been no prospective studies to determine the optimum age for starting the therapy. And since the study would have to be a life study in order to determine these effects, Fischer et al. used historical changes in treatment strategy to perform a retrospective study on the long-term effects of prophylaxis. Three indicators regarding treatment delay were recognized as affecting the severity of arthropathy later in life (the child’s age at start of prophylaxis, the delay after their first joint bleed, and the number of joint bleeds before starting prophylaxis).

Results:

This study highlighted the fact that: delaying the first joint bleed probably has a positive (though clinically unquantified) effect on arthropathy, repeated joint bleeds have a negative impact on joints, other clinical indicators and quality of life, and on-demand therapy’s effectiveness is related to the number of bleeds, the quantity of factor infused and the ability of the patient to infuse correctly and at the right time.

This study did find that after two decades of follow-up, individual patient’s Petterson scores were 8% higher for every year prophylaxis was postponed after the first joint bleed.  It should be noted that this study employed a single radiologist to score the x-rays, thereby eliminating personal practice bias or institutional prejudice.  And while patients in this study had their first joint bleed after the age of two years, those that started prophylaxis soon after the first joint bleed showed little arthropathy in adulthood.  The authors also found that the longer the start of prophylaxis was delayed after the first joint bleed the higher the risk of developing arthropathy.  To this end, some hemophilia centers advocate starting prophylaxis before the first joint bleed (i.e., around the age of one year) while others wait until one or more joint bleeds have occurred.  And by the age of 4.4 years (median for the study) 90% of all patients included in this study had at least one joint bleed (for this study, patients on prophylactic therapy experienced 3.7 joint bleeds annually.  Patient performance is noted in the table below:

Summary of Study 1

_________________________

References:

1. Nilsson IM, Hedner U, Ahlberg A. Haemophilia prophylaxis in Sweden. Acta Paediatr Scand. 1976;65:129-135

2. Löfqvist T, Nilsson IM, Berntorp E, Pettersson H. Haemophilia prophylaxis in young patientsa long-term follow-up. J Intern Med. 1997;241:395-400

3. Aledort LM, Haschmeyer RH, 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

4. Berntorp E, Boulyjenkov V, Brettler D, et al. Modern treatment of haemophilia. Bull World Health Organ. 1995;73:691-701

5. National Hemophilia Foundation. Medical and Scientific Advisory Council (MASAC) recommendations concerning prophylaxis. National Hemophilia Foundation: New York, NY.; 1994. Medical Bulletin 193, Chapter Advisory 197.

6. Astermark J, Petrini P, Tengborn L, Schulman S, Ljung RCR, Berntorp E. Primary prophylaxis in severe haemophilia should be started at an early age but can be individualized. Br J Haematol. 1999;105:1109-1113

7. Nilsson IM, Berntorp E, Lofqvist T, Pettersson H. Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B. J Intern Med. 1992;232:25-32

8. Ljung RCR. Can haemophilic arthropathy be prevented? Br J Haematol. 1998;101:215-219

9. Kreuz W, Escuriola-Ettingshausen C, Funk M, Schmidt H, Kornhuber B. When should prophylactic treatment in patients with haemophilia A and B start?The German experience. Haemophilia. 1998;4:413-417

10. Petrini P, Lindvall N, Egberg N, Blombäck M. Prophylaxis with factor concentrates in preventing hemophilic arthropathy. Am J Pediatr Haematol Oncol. 1991;13:280-287

11. Ljung RCR, Aronis-Vournas S, Kurnik-Auberger K, et al. Treatment of children with haemophilia in Europe: a survey of 20 centres in 16 countries. Haemophilia. 2000;6:619-624

12. Van den Berg HM, Fischer K, Mauser-Bunschoten EP, et al. Long term outcome of individualised prophylactic treatment of children with severe haemophilia. Br J Haematol. 2001;107:561-565.

13. Pettersson H, Nilsson IM, Hedner U, Norehn K, Ahlberg A. Radiologic evaluation of prophylaxis in severe haemophilia. Acta Paediatr Scand. 1981;70:565-570

14. Gilbert MS. Prophylaxis: musculoskeletal evaluation. Semin Hematol. 1993;30:3-6.

15. Liang K-Y, Zeger SL. Longitudinal data analysis using generalized linear models. Biometrika. 1986;73:13-22.

16. Erlemann R, Rosenthal H, Walthers EM, Almeida P, Calleja R. Reproducibility of the Pettersson scoring systeman interobserver study. Acta Radiol. 1989;30:147-15

17. Hamel J, Pohlmann H, Schramm W. Radiological evaluation of chronic hemophilic arthropathy by the Pettersson score: problems in correlation in adult patients. Skeletal Radiol. 1998;17:32-36.

18. Nuss R, Kilcoyne RF, Geraghty S, Wiedel J, Manco Johnson M. Utility of magnetic resonance imaging for management of hemophilic arthropathy in children. J Pediatr. 1993;123:388-392

19. Pollmann H, Richter H, Ringkamp H, Jürgens H. When are children diagnosed as having severa haemophilia and when do they start to bleed? A 10-year single-centre PUP study. Eur J Pediatr. 1999;158:166-170.

20. Onwuzurike N, Warrier I, Lusher JM. Types of bleeding seen during the first 30 months of life in children with severe haemophilia A and B. Haemophilia. 1996;2:137-140.

21. Manco Johnson MJ, Nuss R, Geraghty S, Funk S, Kilcoyne R. Results of secondary prophylaxis in children with severe hemophilia. Am J Hematol. 1994;47:113-117

22. Smith PS, Teutsch SM, Shaffer PA, Rolka H, Evatt B. Episodic versus prophylactic infusions for hemophilia A: a cost-effectiveness analysis. J Pediatr. 1996;129:424-431

23. Liesner RJ, Khair K, Hann IM. The impact of prophyactic treatment on children with severe haemophilia. Br J Haematol. 1996;92:973-978

24. Roosendaal G, Tekoppele JM, Vianen ME, Berg van den HM, Lafeber FPJG, Bijlsma JWJ. Articular cartilage is more susceptible to blood induced damage at young than at old age. J Rheumatol. 2000;27:1740-1744