Çocukluk Çağında Hemofilik Artropati: Patofizyoloji, Tanı ve Tedavi

Year 2021, Volume: 23 Issue: 2, 123 - 128, 30.08.2021

Banu Turhan Yalçın Turhan

https://doi.org/10.18678/dtfd.909300

Abstract

Hemofili hastalarında yaygın olarak gözlenen artropati, yaşam kalitesini ciddi biçimde bozan bir problemdir. Hemofilik artropatide en sık etkilenen eklemler dizler, ayak bilekleri ve dirseklerdir. Eklem içinde gözlenen tek bir kanama bile sinovyum, kıkırdak ve subkondral kemikler dâhil eklemin tüm bileşenlerinde yıkıcı bir takım etkilere neden olabilir. Kıkırdak hasarı ve artropatinin erken dönem değişikliklerinin incelenmesi için daha çok ultrason ve manyetik rezonans görüntüleme kullanımı önerilmektedir. Profilaksi, hemofilik artropati gelişimini önlemek için standart bir tedavi seçeneği olarak gösterilmiştir. Erken yaşta başlanan primer profilaksi kanamaların önlenmesi açısından çok önemlidir ancak adölesan dönemde başlanan sekonder profilaksinin de tekrarlayan kanamaların önlenmesi ve kıkırdak hasarının gelişiminin geciktirilmesi konularında sağladığı ciddi faydaları bilinmektedir. Eklemin kanamaya maruz kalma süresi arttıkça, kıkırdak matriksinin dejenerasyonu ve buna bağlı kıkırdak kaybı da artacağı için eklem içindeki hematomun aspirasyonu hastalığın ilerlemesinin önlenmesinde önemli rol oynar. Profilaksi ve aspirasyonun tekrarlayan kanamaları engelleyemediği durumlarda ise hastalara sinovektomi uygulanması gerekebilir. Gerek medikal gerekse cerrahi yöntemlerle yapılabilen sinovektominin amacı sorunlu sinovyumu ortadan kaldırarak hemofilik artropatinin ilerlemesini önlemektir. Tıbbi sinovektomi (sinoviyortez) radyosinovektomi ve kimyasal sinovektomi olarak iki farklı başlık altında incelenebilir. Bunlardan radyosinovektominin yaklaşık %85 başarı oranı ile kimyasal sinovektomiye göre daha etkili olduğu bildirilmektedir. Tüm bu önlemlerin ilerleyici kıkırdak hasarını önlemede başarısız olduğu durumlarda, açık veya artroskopik sinovektomi, etkilenen eklemin artrodezi ve hatta artroplasti gibi uygulamalara ihtiyaç duyulabilmektedir. Burada, çocukluk çağında gözlenen hemofilik artropatinin patofizyolojisi, teşhis yöntemleri ve tedavisinin güncel literatür eşliğinde tartışılması amaçlanmıştır.

Keywords

hemofili, artropati, sinovit, tanısal görüntüleme

Hemophilic Arthropathy in Children: Pathophysiology, Diagnosis and Management

Abstract

Arthropathy is a serious and common problem in patients with hemophilia impairing the patient’s quality of life seriously. The most commonly affected joints in hemophilic arthropathy are knees, ankles and elbows. Even a single bleeding could cause devastating effects to synovium, cartilage and also subchondral bones. Ultrasound and magnetic resonance imaging have been advocated for the studying of cartilage damage. Prophylaxis has been demonstrated as a standard choice of management to prevent hemophilic arthropathy development. Primary prophylaxis starting at early years of age is very important to prevent hemorrhages but secondary prophylaxis in adolescents has also significant success rates. As the duration of exposure to the blood increases in the joint cavity, degeneration of the cartilage matrix and resultant cartilage loss also increase, so the aspiration of the hematoma from joint plays an important role in prevention of the disease progression. Synovectomy may be required in cases where prophylaxis and aspiration does not prevent the recurrent hemorrhages. The purpose of synovectomy either with medical or surgical methods is to remove the problematic synovium to prevent the progression of hemophilic arthropathy. Medical synovectomy (synoviorthesis) has two basic types; radiosynovectomy and chemical synovectomy and the former one is appearing to be more effective with an about 85% success rates. If all of these measures fail to prevent the progressive cartilage damage, open or arthroscopic synovectomy, arthrodesis of the affected joint or even arthroplasty could be necessary. Here we tried to summarize the pathological mechanism, diagnosis and management of hemophilic arthropathy in children.

Keywords

hemophilia, arthropathy, synovitis, diagnostic imaging

References

• Biggs R, Douglas AS, Macfarlane RG, Dacie JV, Pitney WR, Merskey H. Christmas disease: a condition previously mistaken for haemophilia. Br Med J. 1952;2(4799):1378-82.
• White GC, Rosendaal F, Aledort LM, Lusher JM, Rothschild C, Ingerslev J. Factor VIII and Factor IX Subcommittee. Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 2001;85(3):560.
• Srivastava A, Brewer AK, Mauser-Bunschoten EP, Key NS, Kitchen S, Llinas A, et al. Treatment Guidelines Working Group on Behalf of The World Federation Of Hemophilia. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):e1-47.
• Bertamino M, Riccardi F, Banov L, Svahn J, Molinari AC. Hemophilia care in the pediatric age. J Clin Med. 2017;6(5):54.
• Rodriguez-Merchan EC. Articular bleeding in hemophilia. Cardiovasc Hematol Disord Drug Targets. 2016;16(1):21-4.
• van Vulpen LF, van Meegeren ME, Roosendaal G, Jansen NW, van Laar JM, Schutgens RE, et al. Biochemical markers of joint tissue damage increase shortly after a joint bleed; an explorative human and canine in vivo study. Osteoarthritis Cartilage. 2015;23(1):63-9.
• Manco-Johnson MJ, Soucie JM, Gill JC. Prophylaxis usage, bleeding rates, and joint outcomes of hemophilia, 1999 to 2010: a surveillance project. Blood. 2017;129(17):2368-74.
• Nieuwenhuizen L, Roosendaal G, Coeleveld K, Lubberts E, Biesma DH, Lafeber FP, et al. Haemarthrosis stimulates the synovial fibrinolytic system in haemophilic mice. Thromb Haemost. 2013;110(1):173-83.
• Bhattaram P, Chandrasekharan U. The joint synovium: A critical determinant of articular cartilage fate in inflammatory joint diseases. Semin Cell Dev Biol. 2017;62:86-93.
• Nieuwenhuizen L, Schutgens RE, van Asbeck BS, Wenting MJ, van Veghel K, Roosendaal G, et al. Identification and expression of iron regulators in human synovium: evidence for upregulation in haemophilic arthropathy compared to rheumatoid arthritis, osteoarthritis, and healthy controls. Haemophilia. 2013;19(4):e218-27.
• Bhat V, Olmer M, Joshi S, Durden DL, Cramer TJ, Barnes RF, et al. Vascular remodeling underlies rebleeding in hemophilic arthropathy. Am J Hematol. 2015;90(11):1027-35.
• Hashizume M, Hayakawa N, Mihara M. IL-6 trans-signalling directly induces RANKL on fibroblast-like synovial cells and is involved in RANKL induction by TNF-alpha and IL-17. Rheumatology (Oxford). 2008;47(11):1635-40.
• 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.
• Hakobyan N, Kazarian T, Jabbar AA, Jabbar KJ, Valentino LA. Pathobiology of hemophilic synovitis I: overexpression of mdm2 oncogene. Blood. 2004;104(7):2060-4.
• Roivainen A, Söderström KO, Pirilä L, Aro H, Kortekangas P, Merilahti-Palo R, et al. Oncoprotein expression in human synovial tissue: an immunohistochemical study of different types of arthritis. Br J Rheumatol. 1996;35(10):933-42.
• Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233-55.
• Jansen NW, Roosendaal G, Lafeber FP. Understanding haemophilic arthropathy: an exploration of current open issues. Br J Haematol. 2008;143(5):632-40.
• Srivastava A. Inflammation is key to hemophilic arthropathy. Blood. 2015;126(19):2175-6.
• Acharya SS, Kaplan RN, Macdonald D, Fabiyi OT, DiMichele D, Lyden D. Neoangiogenesis contributes to the development of hemophilic synovitis. Blood. 2011;117(8):2484-93.
• 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.
• Hooiveld MJ, Roosendaal G, van den Berg HM, Bijlsma JW, Lafeber FP. Haemoglobin-derived iron-dependent hydroxyl radical formation in blood-induced joint damage: an in vitro study. Rheumatology (Oxford). 2003;42(6):784-90.
• Zhu H, Meng Y, Tong P, Zhang S. Pathological mechanism of joint destruction in haemophilic arthropathy. Mol Biol Rep. 2021;48(1):969-974.
• Kovacs CS. Hemophilia, low bone mass, and osteopenia/osteoporosis. Transfus Apher Sci. 2008;38(1):33-40.
• van Vulpen LFD, Holstein K, Martinoli C. Joint disease in haemophilia: Pathophysiology, pain and imaging. Haemophilia. 2018;24(Suppl 6):44-9.
• Christensen KR, Kjelgaard-Hansen M, Nielsen LN, Wiinberg B, Alexander Althoehn F, Bloksgaard Poulsen N, et al. Rapid inflammation and early degeneration of bone and cartilage revealed in a time-course study of induced haemarthrosis in haemophilic rats. Rheumatology (Oxford). 2019;58(4):588-99.
• Christoforidis A, Economou M, Papadopoulou E, Kazantzidou E, Farmaki E, Tzimouli V, et al. Comparative study of dual energy X-ray absorptiometry and quantitative ultrasonography with the use of biochemical markers of bone turnover in boys with haemophilia. Haemophilia. 2011;17(1):e217-22.
• Christensen KR, Roepstorff K, Petersen M, Wiinberg B, Hansen AK, Kjelgaard-Hansen M, Nielsen LN. Visualization of haemophilic arthropathy in F8-/- rats by ultrasonography and micro-computed tomography. Haemophilia. 2017;23(1):152-62.
• Pettersson H, Ahlberg A, Nilsson IM. A radiologic classification of hemophilic arthropathy. Clin Orthop Relat Res. 1980;(149):153-9.
• Melchiorre D, Linari S, Innocenti M, Biscoglio I, Toigo M, Cerinic MM, et al. Ultrasound detects joint damage and bleeding in haemophilic arthropathy: a proposal of a score. Haemophilia. 2011;17(1):112-7.
• Kidder W, Nguyen S, Larios J, Bergstrom J, Ceponis A, von Drygalski A. Point-of-care musculoskeletal ultrasound is critical for the diagnosis of hemarthroses, inflammation and soft tissue abnormalities in adult patients with painful haemophilic arthropathy. Haemophilia. 2015;21(4):530-7.
• Di Minno MN, Ambrosino P, Quintavalle G, Coppola A, Tagliaferri A, Martinoli C, et al. Assessment of hemophilic arthropathy by ultrasound: Where do we stand? Semin Thromb Hemost. 2016;42(5):541-9.
• Majeed H, Ahmed H, Sussman MS, Macgowan C, Rayner T, Weiss R, et al. Understanding early hemophilic arthropathy in children and adolescents through MRI T2 mapping. J Magn Reson Imaging. 2021;53(3):827-37.
• Den Uijl IE, De Schepper AM, Camerlinck M, Grobbee DE, Fischer K. Magnetic resonance imaging in teenagers and young adults with limited haemophilic arthropathy: baseline results from a prospective study. Haemophilia. 2011;17(6):926-30.
• Ar MC, Baslar Z, Soysal T. Personalized prophylaxis in people with hemophilia A: challenges and achievements. Expert Rev Hematol. 2016;9(12):1203-8.
• 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.
• Jansen NW, Roosendaal G, Bijlsma JW, Degroot J, Lafeber FP. Exposure of human cartilage tissue to low concentrations of blood for a short period of time leads to prolonged cartilage damage: an in vitro study. Arthritis Rheum. 2007;56(1):199-207.
• Nacca CR, Harris AP, Tuttle JR. Hemophilic arthropathy. Orthopedics. 2017;40(6):e940-6.
• Tat NM, Tat AM, Oner AF, Karaman K, Kaplan S, Can F. Static postural balance evaluation and an investigation of the relationship with joint health in children with severe haemophilia: a controlled cross-sectional study. Haemophilia. 2021;27(2):e245-52.
• Raffini L, Manno C. Modern management of haemophilic arthropathy. Br J Haematol. 2007;136(6):777-87.
• Rodriguez-Merchan EC, Quintana M, De la Corte-Rodriguez H, Coya J. Radioactive synoviorthesis for the treatment of haemophilic synovitis. Haemophilia. 2007;13(Suppl 3):32-7.
• Acharya SS. Hemophilic joint disease - current perspective and potential future strategies. Transfus Apher Sci. 2008;38(1):49-55.
• Dunn AL, Busch MT, Wyly JB, Sullivan KM, Abshire TC. Arthroscopic synovectomy for hemophilic joint disease in a pediatric population. J Pediatr Orthop. 2004;24(4):414-26.
• Acharya SS. Exploration of the pathogenesis of haemophilic joint arthropathy: understanding implications for optimal clinical management. Br J Haematol. 2012;156(1):13-23.
• Ingerslev J, Hvid I. Surgery in hemophilia. The general view: patient selection, timing, and preoperative assessment. Semin Hematol. 2006;43(Suppl 1):S23-6.