Egyptian Rheumatology and Rehabilitation

ORIGINAL ARTICLE
Year
: 2016  |  Volume : 43  |  Issue : 1  |  Page : 35--40

Hemophilic arthropathy: clinical, radiologic, and functional evaluation: a single-center experience in a limited resource country


Hayam M Abdel Ghany1, Hoda M.A. Hassab2, Khaled I El-Noueam3,  
1 Department of Physical Medicine, Rheumatology & Rehabilitation, Faculty of Medicine, Alexandria University, Alexandria, Egypt
2 Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt
3 Department of Radiodiagnosis, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Correspondence Address:
Hayam M Abdel Ghany
Department of Physical Medicine, Rheumatology & Rehabilitation, Faculty of Medicine, Alexandria University, 02030 Alexandria
Egypt

Abstract

Introduction Hemophilia A and B are clinically indistinguishable and are heterogeneous disorders. The severity of bleeding symptoms correlates with the coagulant activity of the deficient factor. Joint bleeding initially leads to independent adverse changes in both the synovial tissue and the articular cartilage. Aim The aim of the present work was to evaluate hemophilic joints clinically, radiologically, and functionally in patients with hemophilic arthropathy. Materials and methods The study was carried out on 30 boys suffering from hemophilic arthropathy; the mean age was 10.6 ± 2.95 years. All patients were subjected to thorough history taking and local physical examination of the «SQ»target joint«SQ». Functional Independence Score in Hemophilia (FISH) and the Pettersson scoring system were assessed for all patients. Results The age at first hemarthrosis decreased with the severity of hemophilia, whereas the number of bleeds/year and the number of joints affected increased with the severity, and the results were statistically significant. A statistically significant positive correlation was found between the Pettersson score and both the age of the patients and the number of bleeds/year. However, a negative correlation was found with factor activity level. In contrast, the FISH score had a significant positive correlation with factor activity level. Conclusion A significant decrease in the functional ability was demonstrated on the basis of the severity of hemophilia. Both the FISH and Pettersson scoring systems are of great importance in assessing patients with hemophilic arthropathy.



How to cite this article:
Abdel Ghany HM, Hassab HM, El-Noueam KI. Hemophilic arthropathy: clinical, radiologic, and functional evaluation: a single-center experience in a limited resource country.Egypt Rheumatol Rehabil 2016;43:35-40


How to cite this URL:
Abdel Ghany HM, Hassab HM, El-Noueam KI. Hemophilic arthropathy: clinical, radiologic, and functional evaluation: a single-center experience in a limited resource country. Egypt Rheumatol Rehabil [serial online] 2016 [cited 2019 Oct 21 ];43:35-40
Available from: http://www.err.eg.net/text.asp?2016/43/1/35/177425


Full Text

 Introduction



Hemophilia A and B are clinically indistinguishable and are heterogeneous disorders [1],[2] . Their clinical manifestations are identical, with an increased tendency for musculoskeletal, soft tissue, and mucocutaneous bleeding. The activity level of the deficient factor affects the severity of bleeding [1],[3],[4] .

Spontaneous bleeding into a joint (hemarthrosis) and muscle is the most frequent manifestation of severe hemophilia. Joint bleeding accounts for 90% of bleeding in hemophilic patients [1],[5] . Joint bleeding initially leads to independent adverse changes in both the synovial tissue and the articular cartilage. Both synovial inflammatory changes and cartilage damage affect each other [6] .

Hemarthroses also have their impact on bone. Enlargement of the epiphysis and growth disturbance are present in hemophilic patients as a sequelae of repeated joint bleeds; moreover, subchondral changes may occur in the form of osteoporosis, subchondral cyst formations, and both erosions and osteophyte formation. Furthermore, in severe forms of hemophilic arthropathy, ankylosis, fusion of the bones can occur; a phenomenon also observed in severe osteoarthritis [7],[8] .

The Pettersson score is a detailed radiologic classification of hemophilic joints that has been adopted by the World Federation of Hemophilia (WFH). It estimates joint destruction radiologically [9] .

Gilbert score is a physical examination score. It assesses joint health in patients with hemophilic arthropathy [10],[11] .

Functional Independence Score in Hemophilia (FISH) is a performance-based instrument used to objectively assess musculoskeletal function of patients with hemophilia. FISH measures the patient's independence in performing seven activities under three categories: self-care (grooming and eating, bathing, and dressing), transfers (chair and floor), and mobility (walking and step climbing) [12] .

The aim of the present work was to evaluate hemophilic joints clinically, radiologically, and functionally.

 Materials and methods



The study was carried out on 30 boys with hemophilia and with a history of previous joint bleeding. They were selected from those attending the Outpatient Hematology Clinic of Alexandria University Children's Hospital at Elshatby. All patients had at least one target joint. 'Target joint' was defined as a joint with a history of clinical symptoms of pain, tenderness, swelling, or locking.

This study was explained to the participants, and informed consent was taken from parents of all children included in the study.

All hemophilic patients included in the study were subjected to the following:

History taking, including age at first hemarthrosis (years), the number of bleedings (last year) and number of joints affected, and family history of similar condition.Assessment of factor activity level: mild (5-40% of normal activity), moderate (1-5% of normal activity), and severe (<1% of normal activity) [3],[4] .Evaluation of the target joint using the WFH clinical score (Gilbert score) [10],[11] .FISH [12] .Conventional frontal and lateral radiographs of the target joint, which was scored according to the Pettersson score by a radiologist [9],[11] .

Statistical analysis of the data

Data were analyzed using Statistical Package for Social Sciences, version 20.0, 2nd ed. (2002; London, NewYork, Arnold). Qualitative data were described using number and percentage. Quantitative data were described using mean, SD median, and minimum and maximum. For abnormally distributed data (data distribution that was significantly deviated from normal), more than two populations were analyzed using the Kruskal-Wallis test. Correlations between two quantitative variables were assessed using Spearman's coefficient.

Significance was considered at P value less than 0.05.

 Results



The age of the studied boys ranged from 6 to 16 years, with a mean of 10.6 ± 2.95 years. Among the 30 hemophilic patients, 26 (86.7%) patients had hemophilia A and four (13.3%) patients had hemophilia B. Nineteen (63.3%) patients had a positive family history of similar condition and 50% of the patients had positive consanguinity.

The knee was the most affected joint in 22 (73.3%) patients, followed by ankle in five (16.7%) patients, only two (6.7%) patients had elbow affection, and one (3.3%) patient had shoulder affection.

Fifteen (50%) of the studied hemophilic patients had severe hemophilia, seven (23.3%) patients had moderate, and eight (26.7%) patients had mild hemophilia.

The age at first hemarthrosis decreased with the increased severity of hemophilia, whereas the number of bleeds/year and the number of joints affected increased with the increased severity and the results were statistically significant (P = 0.001, P < 0.001, and P = 0.048, respectively) ([Table 1]).{Table 1}

Clinical evaluation of the target joint using the Gilbert score is presented in [Table 2]. There was a significant inverse correlation between the WFH clinical (Gilbert) score and factor activity level (r = −0.538, P = 0.002) ([Figure 1]).{Figure 1}{Table 2}

FISH score was highest in patients with mild hemophilia, with a mean of 28.5 ± 2.38, and the lowest among those with severe hemophilia, with a mean of 26.07 ± 4.27, and this result showed statistical significance (P = 0.036) ([Table 3]).{Table 3}

There was a significant positive correlation between the FISH score and factor level (r = 0.602, P < 0.001) ([Figure 2]).{Figure 2}

There was a significant positive correlation between the Pettersson score and the age of the patients and number of bleeds/year ([Figure 3]a and b).{Figure 3}

Moreover, Pettersson score had a statistically significant negative correlation with factor activity level ([Figure 4]).{Figure 4}

 Discussion



Hemophilic arthropathy is the consequence of recurrent bleeding into the joint in patients with hemophilia and is the main cause of morbidity in these patients. This study was carried out to evaluate hemophilic joints clinically, radiologically, and functionally.

The most commonly affected joint in the present study was the knee in 73.3% of the cases, ankle in 16.7% of cases, elbow in 6.7% of cases, followed by shoulder in 3.3% of cases (one patient). This finding is in agreement with that of Jansen et al. [13] , who found that the three large joints (ankle, knee, and elbow) were the most commonly affected. The knee and ankle have a weight-bearing function, as a result they bleed more often. Shoulders and hips are better supported and thus bleed less [14],[15] .

On comparing the bleeding history (age at first hemarthrosis, number of bleeds/year, and number of joints affected) with the severity of factor activity level, statistical significance was detected implying that a decrease in factor level resulted in lower age of hemarthrosis and increase in the number of bleeds/year, and an increase in the number of joints affected too. Data from the Universal Data Collection showed that patients with severe hemophilia were at a higher risk of developing a target joint than those with moderate or mild hemophilia (33.1 vs. 18.8% and 5%, respectively) [16] .

Pollmann et al. [17] reported that, in nearly half of all children with severe hemophilia, the initial hemarthrosis occurs during the first year of life. Fischer et al. [18] added that 90% of youngsters who are severely deficient in FVIII or FIX experience at least one joint hemorrhage before the age of 4.5 years.

In the present study, the mean age of first hemarthrosis in severe hemophilic patients was 2.22 ± 1 years and ranged from 0.5 to 4.0 years.

Individuals with severe hemophilia are more likely to develop joint problems and reduced range of motion (ROM) of joints [19],[20] . ROM has been the most utilized measurement for evaluating the effects of intervention on joint health [21] . In the current study, 15 patients had severe hemophilia and seven patients had moderate, and all patients had limited ROM with variable degrees. ROM limitation increased significantly with more frequent bleeding episodes [20] . If patients with severe disease do not receive appropriate treatment, they will develop clinical symptoms: pain, swelling, and reduced ROM by early adolescence that will severely affect their health and quality of life [19],[22],[23] .

In the current study, FISH score was significantly higher in those with mild hemophilia than in patients with moderate or severe hemophilia.

Because our patients receive on-demand therapy, the severity of the factor deficiency will increase the number of bleeds/year and thus more degenerative changes within the joint that correspondingly will impair patients' function. This was supported by previous studies [24],[25] .

The present study showed a statistically significant negative correlation between the Pettersson score and factor activity level. Similar results were reported by Hassan et al. [24]. Patients with severe degree of hemophilia have more radiological changes with Pettersson, as intra-articular bleeding accounted for more than 90% of all serious bleeding events in those patients [26] .

Enlargement of epiphysis (30%) and irregular subchondral surface (32%) were the most frequent observation, whereas osteoporosis was less observed (13.3%). This was supported by Erlemann et al. [27] , who studied the degree of osteoarthropathy in 40 hemophilic children using the Pettersson score.

Fischer et al. [18] reported that the Pettersson radiological score increases by 1 point for every three joint hemorrhages occurring after 5 years of age. In this study, the positive significant correlation between Pettersson score and number of joint bleeds/year was in accordance with that reported by Van Dijk et al. [28] , who assessed joint damage using Pettersson score based on age groups in severe hemophiliacs and reported that the score increased with the cumulative number of joint bleeds.

 Conclusion



A significant decrease in the functional ability was demonstrated on the basis of the severity of hemophilia. The most commonly affected joints in patients receiving on-demand therapy are the knees, followed by the elbows and ankles.

In hemophilic patients, radiographic scoring of the joints using the Pettersson scoring system proved to be useful, available, and cheap for prediction of the degree of hemophilic arthropathy.

Acknowledgements

Dr. Hayam Mostafa and Dr. Hoda Hassab performed the research, analyzed the data, and wrote the paper. Dr. Khaled El-Noueam performed the radiological evaluation of the participants.

The manuscript has been read and approved by all authors, that the requirements for authorship as stated earlier in this document have been met, and that each author believes that the manuscript represents an honest work.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Jayandharan GR, Srivastava A. Hemophilia: genetics, diagnosis and treatment. Genet Syndr Gene Ther 2011; 1 :1-12.
2 Hoffman M. A cell-based model of coagulation and the role of factor VIIa. Blood Rev 2003; 17 (Suppl 1):1-5.
3 Paul-Scott J, Robert R. Montgomery hereditary clotting factor deficiencies (bleeding disorders). In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, (editors) Nelson textbook of pediatrics. 19th ed. Philadelphia: Saunders Elsevier; 2011. 470 :1699-1701.
4 White GC II, 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 : 560.
5 Rodriguez-Merchan EC, Jimenez-Yuste V, Aznar JA, Hedner U, Knobe K, Lee CA, et al. Joint protection in haemophilia. Haemophilia 2011; 17 (Suppl 2): 1-23.
6 Roosendaal G, Lafeber F. Prophylactic treatment for prevention of joint disease in hemophilia - cost versus benefit. N Engl J Med 2007; 357 : 603-605.
7 Jansen NW, Roosendaal G, Lafeber FP. Understanding haemophilic arthropathy: an exploration of current open issues. Br J Haematol 2008; 143 :632-640.
8 Jacobson JA, Girish G, Jiang Y, Sabb BJ. Radiographic evaluation of arthritis: degenerative joint disease and variations. Radiology 2008; 248 :737-747.
9 Pettersson H, Ahlberg A, Nilsson IM. A radiologic classification of hemophilic arthropathy. Clin Orthop Relat Res 1980; 149 : 153-153159.
10De Kleijn P, Heijnen L, Van Meeteren NL. Clinimetric instruments to assess functional health status in patients with haemophilia: a literature review. Haemophilia 2002; 8 :419-427.
11Pergantou H, Matsinos G, Platokouki H, Papadopoulos A, Aronis S. An attempt to improve the clinical scale for assessment of haemophilic arthropathy in children. J Pediatr Orthop B 2009; 18 :204-210.
12Poonnoose PM, Thomas R, Keshava SN, Cherian RS, Padankatti S, Pazani D et al. Psychometric analysis of the Functional Independence Score in Haemophilia (FISH). Haemophilia 2007; 13 :620-626.
13Jansen NW, Roosendaal G, Lundin B, Heijnen L, Mauser-Bunschoten E, Bijlsma JW, et al. The combination of the biomarkers urinary C-terminal telopeptide of type II collagen, serum cartilage oligomeric matrix protein, and serum chondroitin sulfate 846 reflects cartilage damage in hemophilic arthropathy. Arthritis Rheum 2009; 60 :290-298.
14Valentino LA, Taylor A. Hemophilia Clinical Consults: hemophilic arthropathy, reduced bone density and preventive strategies. Clinical Consults 2011; 1 :1.
15Stephensen D, Tait RC, Brodie N, Collins P, Cheal R, Keeling D, et al. Changing patterns of bleeding in patients with severe haemophilia A. Haemophilia 2009; 15 :1210-1214.
16Centers for Disease Control and Prevention. Report on the Universal Data Collection Program. 2005; 7: 1-39. Available at www.cdc.gov/ncbddd/hbd/documents/ UDC7(1).pdf.
17Pollmann H, Richter H, Ringkamp H, Jurgens H. When are children diagnosed as having severe haemophilia and when do they start to bleed? A 10-year single-centre PUP study. Eur J Pediatr 1999; 158 (Suppl 3):S166-S166S170.
18Fischer K, van der Bom JG, Mauser-Bunschoten EP, Roosendaal G, Prejs R, de Kleijn P, et al. The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia. Blood 2002; 99 :2337-2341.
19Knobe K, Berntorp E. Haemophilia and joint disease: pathophysiology, evaluation, and management. J Comorbidity 2011; 1 :51-59.
20Soucie JM, Cianfrini C, Janco RL, Kulkarni R, Hambleton J, Evatt B, et al. Joint range-of-motion limitations among young males with hemophilia: prevalence and risk factors. Blood 2004; 103 :2467-2473.
21Raffini L, Manno C. Modern management of haemophilic arthropathy. Br J Haematol 2007; 136 :777-787.
22Khawaji M, Astermark J, Von Mackensen S, Akesson K, Berntorp E. Bone density and health-related quality of life in adult patients with severe haemophilia. Haemophilia 2011; 17 :304-311.
23Blanchette P, Rivard G, Israels S, Robinson S, Ali K, Walker I, et al. A survey of factor prophylaxis in the Canadian haemophilia A population. Haemophilia 2004; 10 :679-683.
24Hassan TH, Badr MA, El-Gerby KM. Correlation between musculoskeletal function and radiological joint scores in haemophilia A adolescents. Haemophilia 2011; 17 :920-925.
25Tlacuilo-Parra A, Villela-Rodriguez J, Garibaldi-Covarrubias R, Soto-Padilla J, Orozco-Alcala J. Functional independence score in hemophilia: a cross-sectional study assessment of Mexican children. Pediatr Blood Cancer 2010; 54 :394-397.
26Valentino LA. Blood-induced joint disease: the pathophysiology of hemophilic arthropathy. J Thromb Haemost 2010; 8 :1895-1902.
27Erlemann R, Pollmann H, Reiser M, Almeida P, Peters PE. Staging of hemophilic osteoarthropathy using the Pettersson score. Pathogenesis, early diagnosis, and prophylaxis for chronic hemophilic synovitis. Clin Orthop Relat Res 1997; 343 :74-80.
28Van 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 :438-443.