Современные представления о патогенезе гемофилической артропатии

Основным проявлением гемофилии являются кровоизлияния в крупные суставы. Гемартроз запускает патогенети- ческий каскад, который может привести к развитию гемофилической артропатии. Кровь оказывает негативное влия- ние на состояние хрящевой ткани и синовиальной оболочки сустава. В ходе многочисленных исследований была показана ключевая роль профилактической гемостатической терапии в предотвращении развития гемофилической артропатии. Знание фармакокинетических характеристик препарата позволяет корректировать дозы вводимого кон- центрата фактора свертывания крови и избегать длительного снижения активности дефицитного фактора в крови менее 1%, что дает возможность предотвратить возникновение спонтанных кровотечений и развитие артропатии.

гемофилия, гемартроз, гемофилическая артропатия, профилактическая гемостатическая терапия, haemophilia, haemarthrosis, haemophilic arthropathy, prophylactic treatment

1. Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1-47

2. Roosendaal G, Lafeber FP. Pathogenesis of haemophilic arthropathy. Haemophilia. 2006;12(Suppl. 3):117-21

3. Gringeri A, Ewenstein B, Reininger A. The burden of bleeding in haemophilia: is one bleed too many? Haemophilia. 2014;20(4):459-63

4. Valentino LA, Hakobyan N, Rodriguez N, Hoots WK. Pathogenesis of haemophilic synovitis: experimental studies on blood-induced joint damage. Haemophilia. 2007;13(Suppl. 3):10-3

5. Roy S, Ghadially FN. Synovial membrane in experimentally-produced chronic haemarthrosis. Ann Rheum Dis. 1969;28(4):402-14

6. Madhok R, York J, Sturrock RD. Haemophilic arthritis. Ann Rheum Dis. 1991;50(8):588-91

7. Mainardi CL, Levine PH, Werb Z, Harris ED Jr. Proliferative synovitis in hemophilia: biochemical and morphologic observations. Arthritis Rheum. 1978;21(1):137-44

8. Rodríguez-Merchán EC. Pathogenesis, early diagnosis, and prophylaxis for chronic hemophilic synovitis. Clin Orthop Relat Res. 1997;(343):6-11

9. Rodriguez-Merchan EC. Haemophilic synovitis: basic concepts. Haemophilia. 2007;13(Suppl. 3):1-3

10. Dabbagh AJ, Trenam CW, Morris CJ, Blake DR. Iron in joint inflammation. Ann Rheum Dis. 1993;52(1):67-73

11. Hough AJ, Banfield WG, Sokoloff L. Cartilage in hemophilic arthropathy. Ultra- structural and microanalytical studies. Arch Pathol Lab Med. 1976;100(2):91-6

12. Stein H, Duthie RB. The pathogenesis of chronic haemophilic arthropathy. J Bone Joint Surg Br. 1981;63B(4):601-9

13. Roosendaal G, Vianen ME, Wenting MJ, van Rinsum AC, van den Berg HM, Lafeber FP, et al. Iron deposits and catabolic properties of synovial tissue from patients with haemophilia. J Bone Joint Surg Br. 1998;80(3):540-5

14. Nishiya K. Stimulation of human synovial cell DNA synthesis by iron. J Rheumatol. 1994;21(10):1802-7

15. Wen FQ, Jabbar AA, Chen YX, Kazarian T, Patel DA, Valentino LA. C-myc proto- oncogene expression in hemophilic synovitis: in vitro studies of the effects of iron and ceramide. Blood.2002;100(3):912-6

16. Roosendaal G, TeKoppele JM, Vianen ME, van den Berg HM, Lafeber FP, Bijlsma JW. Blood-induced joint damage: a canine in vivo study. Arthritis Rheum. 1999; 42(5):1033-9

17. Jansen NW, Roosendaal G, Wenting MJ, Bijlsma JW, Theobald M, Hazewinkel HA, et al. Very rapid clearance after a joint bleed in the canine knee cannot prevent adverse effects on cartilage and synovial tissue. Osteoarthritis Cartilage. 2009;17(4):433-40

18. Jansen NW, Roosendaal G, Lafeber FP. Understanding haemophilic arthropathy: an exploration of current open issues. Br J Haematol. 2008;143(5):632-40

19. Hooiveld M, Roosendaal G, Vianen M, van den Berg M, Bijlsma J, Lafeber F. Blood- induced joint damage: longterm effects in vitro and in vivo. J Rheumatol. 2003;30(2):339-44

20. Hooiveld MJ, Roosendaal G, Jacobs KM, Vianen ME, van den Berg HM, Bijlsm JW, Lafeber FP. Initiation of degenerative joint damage by experimental bleeding combined with loading of the joint: a possible mechanism of hemophilic arthropathy. Arthritis Rheum. 2004;50(6):2024-31

21. Hooiveld M, Roosendaal G, Wenting M, van den Berg M, Bijlsma J, Lafeber F. Short-term exposure of cartilage to blood results in chondrocyte apoptosis. Am J Pathol. 2003;162(3):943-51

22. Burkhardt H, Schwingel M, Menninger H, Macartney HW, Tschesche H. Oxygen radicals as effectors of cartilage destruction. Direct degradative effect on matrix components and indirect action via activation of latent collagenase from polymorphonuclear leukocytes. Arthritis Rheum. 1986;29(3):379-87

23. Nathalie NW, Roosendaal G, Lafeber FP. Understanding haemophilic arthropathy: an exploration of current open issues. Br J Haematol. 2008;143(5):632-40

24. Pettersson H, Ahlberg A, Nilsson IM. A radiologic classification of haemophilic arthropathy. Clin Orthop Relat Res. 1980;(149):153-9

25. Pergantou H, Matsinos G, Papadopoulos A, Platokouki H, Aronis S. Comparative study of validity of clinical, X-ray and magnetic resonance imaging scores in evaluation and management of haemophilic arthropathy in children. Haemophilia. 2006;12(3):241-7

26. Nuss R, Kilcoyne RF, Geraghty S, Shroyer AL, Rosky JW, Mawhinney S, et al. MRI findings in haemophilic joints treated with radiosynoviorthesis with development of an MRI scale of joint damage. Haemophilia. 2000;6(3):162-9

27. Nilsson IM, Berntorp E, Löfqvist T, Pettersson H. Twenty-five year’s experience of prophylactic treatment in severe haemophilia A and B. J Intern Med. 1992; 232(1):25-32

28. Aledort L. Experience with prophylactic treatment in USA. Clinical benefits; a multi-central view. In: Royal Society of Medicine Services Ltd, Round Table Series No. 25. Oxford: Alden Press; 1991:26-31

29. Wood K, Omer A, Shaw MT. Haemophilic arthropathy. A combined radiological and clinical study. Br J Radiol. 1969;42(499):498-505

30. Funk MB, Schmidt H, Becker S, Escuriola C, Klarmann D, Klingebiel T, et al. Modified magnetic resonance imaging score compared with orthopaedic and radiological scores for the evaluation of haemophilic arthropathy. Haemophilia. 2002;8(2):98-103

31. Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne R, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357(6):535-44

32. den Uijl IE, Fischer K, Van Der Bom JG, Grobbee DE, Rosendaal FR, Plug I. Clinical outcome of moderate haemophilia compared with severe and mild haemophilia. Haemophilia. 2009;15(1):83-90

33. Olivieri M, Kurnik K, Pfluger T, Bidlingmaier C. Identification and long-term observation of early joint damage by magnetic resonance imaging in clinically asymptomatic joints in patients with haemophilia A or B despite prophylaxis. Haemophilia. 2012;18(3):369-74

34. Kraft J, Blanchette V, Babyn P, Feldman B, Cloutier S, Israels S, et al. Magnetic resonance imaging and joint outcomes in boys with severe hemophilia A treated with tailored primary prophylaxis in Canada. J Thromb Haemost. 2012;10(12): 2494-502

35. Biggs R, MacFarlane RG. Haemophilia and related conditions: a survey of 187 cases. Br J Haematol. 1958;4(1):1-27

36. Den Uijl IE, Mauser Bunshoten EP, Roosendaal G, Schutgens RE, Biesma DH, Grobbee DE, et al. Clinical severity of haemophilia A: does the classification of the 1950s still stand? Haemophilia. 2011;17(6):849-53

37. Van Dijk K, Fischer K, van der Bom JG, Grobbee DE, van den Berg HM. Variability in clinical phenotype of severe haemophilia: the role of the first joint bleed. Haemophilia. 2005;11(5):438-43

38. Ahlberg A. Haemophilia in Sweden.VII. Incidence, treatment and prophylaxis of arthropathy and other musculo-skeletal manifestations of haemophilia A and B. Acta Orthop Scand. 1965(Suppl. 77):3-132

39. Astermark J, Petrini P, Tengborn L, Schulman S, Ljung R, Berntorp E. Primary prophylaxis in severe haemophilia should be started at an early age but can be individualized. Br J Haematol. 1999;105(4):1109-13

40. Collins PW, Fischer K, Morfini M, Blanchette VS, Björkman S; International Prophylaxis Study Group Pharmacokinetics Expert Working Group. Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia. Haemophilia. 2011;17(1):2-10

41. Valentino LA, Mamonov V, Hellmann A, Quon DV, Chybicka A, Schroth P, et al. A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management. J Thromb Haemost. 2012;10(3):359-67

42. Hilberg T, Herbsleb M, Puta C, Gabriel HH, Schramm W. Physical training increases isometric muscular strength and proprioceptive performance in haemophilic subjects. Haemophilia. 2003;9(1):86-93

43. Skinner M, Street A. Global data and haemophilia care trends: commentary. Haemophilia. 2010;16(1):18-9

44. Othman M, Powell S, Chirinian Y, Hegadorn C, Hopman W, Lillicrap D. Thrombo- elastography reflects global hemostatic variation among severe haemophilia A dogs at rest and following acute exercise. Haemophilia. 2009;15(5):1126-34.

45. Koch B, Luban NL, Galioto FM Jr, Rick ME, Goldstein D, Kelleher JF Jr. Changes in coagulation parameters with exercise in patients with classic hemophilia. Am J Hematol. 1984;16(3):227-33