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 Table of Contents  
Year : 2016  |  Volume : 41  |  Issue : 4  |  Page : 168-173

Joint health in Egyptian children with hemophilia A: what are the affecting factors?

1 Department of Pediatrics, University Hospital, Fayoum University, Egypt
2 Department of Physiotherapy, Misr University for Science and Technology, Egypt

Date of Submission09-Sep-2016
Date of Acceptance22-Sep-2016
Date of Web Publication20-Jan-2017

Correspondence Address:
Atwa T.H. Zeze
Department of Pediatrics, University Hospital, Fayoum University, 63514
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1110-1067.198651

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Background Hemophilia A is an X-linked recessive disorder. Patients experience spontaneous and trauma-induced bleeds. Recurrent joint bleeds lead to progressive disability. Attaining healthy joint is the main goal of hemophilia treatment. The objective of our study was to evaluate joint health and factors affecting it in hemophilia patients who were on episodic treatment.
Methodology This is a prospective observational study. Hemophilia joint health score was performed on 42 children with severe hemophilia who were selected from pediatric hematology clinics. Factors that may affect hemophilia joint health score were evaluated. These factors were age, age at first joint bleed, frequency of hemarthrosis per year, BMI, parents’ level of education, residence, hepatitis C virus infection, performing physiotherapy regularly, and performing conservative measures upon active bleeding (ice, rest, compression, and elevation). Data were analyzed using Statistical Package for Social Sciences.
Results The mean total joint score was 12.3±7.3. Knee, ankle, and elbow were the target joints in 28.6, 26.2, and 26.2% of patients, respectively. Older patient age, earlier age at first hemarthrosis, and frequent hemarthrosis were associated with higher joint score. Performing physiotherapy was associated with a lower joint score. No significant effects could be elicited as regards other studied factors.
Conclusion Older patients and those with frequent hemarthrosis were more prone to joint damage. Performing physiotherapy should be encouraged, as it can improve joint health in hemophilia patients.

Keywords: hemophilia, joint health, risk factors

How to cite this article:
Zeze AT, Hanaa EH, Nejm Eldin TR. Joint health in Egyptian children with hemophilia A: what are the affecting factors?. Egypt J Haematol 2016;41:168-73

How to cite this URL:
Zeze AT, Hanaa EH, Nejm Eldin TR. Joint health in Egyptian children with hemophilia A: what are the affecting factors?. Egypt J Haematol [serial online] 2016 [cited 2022 Aug 13];41:168-73. Available from: http://www.ehj.eg.net/text.asp?2016/41/4/168/198651

  Introduction Top

Hemophilia A is an X-linked recessive disorder caused by a deficiency of coagulation factor VIII. Patients with hemophilia A experience spontaneous and trauma-induced bleeds. Joint bleeds lead to hemophilic arthropathy resulting in progressive disability [1].

Replacement of the deficient coagulation factor with concentrates is the mainstay of hemophilia treatment, which can be administered episodically or regularly. Episodic therapy (i.e. administration of concentrates when the bleeding issues) has been shown to decrease mortality and to slow the progression to arthropathy, but not to prevent it [2]. Prophylactic treatment (long-term, regular, continuous administration of concentrates) is the most effective method to prevent bleeding and bleeding-related complications [3]. In most developing countries, there is a lack of resources to buy the necessary quantities of coagulation factor concentrate. Therefore, treatment regimen in these countries has remained predominantly episodic [4]. Optimal treatment involves a combination of replacement therapy, with conservative measures (rest, ice, compression, elevation), which may be an inexpensive and efficient treatment option to diminish the unfavorable effects of joint bleedings and to increase the functional independence [5],[6]. Performing regular physiotherapy sessions may improve musculoskeletal health by regulating joint mobilization and preventing vicious attitudes and muscle atrophy [7].

There are insufficient studies that investigate the impact of applying these measures on joint health. The objective of our study was to evaluate joint health in hemophilia A patients who were on episodic treatment using hemophilia joint health score, version 2.1 (HJHS). The benefits of applying conservative measures and physiotherapy as adjunctive treatment were studied. Other factors that may affect HJHS (sociodemographic and clinical factors) among these patients were investigated.

  Patients and methods Top

Study design

The study was designed as a prospective observational study. The study was performed at the pediatric hematology clinic of a University hospital. Patients’ cohort included male individuals with severe hemophilia A who were followed up over a period of 10 months between October 2015 and July 2016 to assess the HJHS and factors affecting it.


A total of 42 children with severe hemophilia A were included in the study. Nearly all patients who met the inclusion criteria were included in the study.

Patients aged 3–16 years diagnosed as having severe hemophilia A and for whom access to their medical and follow-up records were available were included in the study.

Exclusion criteria were as follows:

  1. Patients aged less than 3 years or more than 16 years.
  2. Patients with coagulation disorders other than hemophilia A.
  3. Patients with associated chronic medical illness apart from hepatitis C and B and HIV.

Data collected

Data about age, date at first joint bleed, frequency of hemarthrosis, and target joint (joint with repeated bleed) were determined from the patient record and reported.

Addresses of the patients were recorded to detect accessibility to the nearest medical center with replacement treatment access. Parental degrees of education were also reported.

History of compliance to conservative measures at periods of active bleeding was taken from the parents. These conservative measures were as follows: applying ice (ice was applied for 5–15 min during the first 6 h), rest (joint immobilization and no weight-bearing), externally applied compression, and elevation in the first 48–72 h postinjury, to prevent further hemorrhage [5],[6],[8],[9],[10].

Performing weekly physiotherapy sessions (in the form of hydrotherapy and electrotherapy) was also detected from the patient record.

Measured weight and heights were obtained using appropriate calibrated devices, and then BMIs were calculated.

The musculoskeletal system of children with hemophilia was assessed with HJHS, version 2.1 developed by the international prophylaxis study group [11] and validated as a sensitive tool that is able to ascertain joint damage even at an early stage and at early young age [12]. HJHS was operated with the same examiner for all cases, who is the study author. When the total joint score (the sum of six joint scores: left and right elbow, left and right knee, left and right ankle) is added to the global gait score, an HJHS total score ranging from 0 (healthy score) to 124 (worst score) is obtained. We calculated the total joint score without adding global gait score.

Blood samples for hepatitis B, C, and human immunodeficiency virus serological test were collected.

All procedures performed were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from parents, next of kin, caretakers, or guardians (informants) of all cases who participated in the study, as our participants are children.

Statistical analysis

Statistical analysis was conducted as follows:

  1. Data were collected and coded to facilitate data manipulation and double-entered into Microsoft Access, and data analysis was performed using SPSS software, version 18 under Windows 7 (Chicago, USA).
  2. Simple descriptive analyses were performed in the form of numbers and percentages for qualitative data, and arithmetic means as central tendency measurement, SDs as measure of dispersion for quantitative parametric data, and inferential statistic test.

For quantitative parametric data

The following tests were used for quantitative parametric data:

  1. Independent Student’s t-test was used to compare measures of two independent groups of quantitative data.
  2. One-way analysis of variance test was used to compare more than two independent groups of quantitative data.

For quantitative nonparametric data

The following tests were used for quantitative nonparametric data:

  1. Kruskal–Wallis test was used to compare more than two independent groups.
  2. Mann–Whitney test was used to compare two independent groups.

For qualitative data

The following tests were used for qualitative data:

  1. χ2-test was to compare two or more than two qualitative groups.
  2. Multiple linear regressions were used to test the association between quantitative dependent and independent variables and detection of risk factors.
  3. The level P of 0.05 or less was considered the cutoff value for significance.

  Results Top

The study included 42 male patients with severe hemophilia. The mean age of study patients was 7.8±3.8 years, and the mean BMI was 21±8.4 kg/m2. Mean urea level was 26.8±8.9 mg/dl and mean creatinine level was 0.45±0.18 mg/dl. The mean age of presentation in the study patients was 11.6±5.4 months, the mean frequency of hemoarthritis was 8.2±8.2, and the mean total joint score was 12.3±7.3. In all, 57.1% of patients are resident in rural area and 42.9% are from urban areas. As regards parents’ education level, around half of the fathers and mothers had middle and high education levels. In all, 47.6% of patients had other siblings affected with hemophilia. With regard to the conservative treatment used, 40.5% performed regular weekly sessions of physiotherapy. Upon active joint bleeding, ice fomentation, rest, elevation, and compression were done by 73.8, 45.2, 52.4, and 59.5% of patients, respectively ([Table 1]).
Table 1 Description to clinical and sociodemographic characters of hemophilic patients (n=42)

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As regards the target joint (joint with frequent bleeding), knee, elbow, and ankle were the target joints in 28.6, 26.2, and 19% of the patients, respectively ([Table 1]).

By univariate test, there were no statistical significant differences in HJHS with P-value of more than 0.05 as regards the effect of HCV seropositivity, the presence of other sibling affection, residence, or parental educational level ([Table 2]).
Table 2 Comparisons of study variables with regard to the level of total joint score

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There was a statistically significant negative effect of physiotherapy on HJHS, which means better joint health on performing physiotherapy. There were no statistically significant differences with P-value of more than 0.05 as regards the effect of ice, rest, elevation, or compression on HJHS ([Table 3]).
Table 3 Relation between total joint score and different treatment modalities

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There were statistically significant positive correlations with a P-value of less than 0.05 between HJHS with each of age of patients and frequency of heamoartrosis ([Figure 1] and [Table 2]). However, there were no statistically significant correlations with P-value of more than 0.05 as regards BMI ([Table 4]).
Figure 1 Correlation between total joint score and frequency of hemarthrosis.

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Table 4 Correlation between total joint score and different variables among hemophilic patients

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The multivariate logistic regression model analysis was conducted to explore the explanatory power of different risk factors on HJHS; it illustrated that there were statistically significant predictors, with P-value of less than 0.05, to age of patients, age of presentation, and frequency of hemarthrosis and performing physiotherapy with P-value of 0.01, 0.01, and <0.001, 0.006, respectively ([Table 5]).
Table 5 Stepwise regression analysis to determine the risk factors affecting total joint score among hemophilic patients

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  Discussion Top

There are variations in the treatment options of hemophilia all over the world. Developing countries contain about 80% of hemophilic patients; however, they receive only 20% of the financial plan of the world as regards hemophilia care [13],[14]. The mode and quantity of replacement of factor VIII concentrate are the most important determinants of long-term musculoskeletal outcome [15],[16],[17]. In our study locality, factor VIII concentrate is unavailable as an option for prophylaxis. The lone treatment option is an episodic (on-demand) one.

Our results showed that the more frequent cases of hemarthrosis per year were associated with higher joint score, which indicates worse joint health. Repeated hemarthrosis episodes stimulate a proliferative and destructive chronic synovitis with progressive joint destruction, known as hemophilic arthropathy. Active joint bleeding is associated with increased level of angiogenic and inflammatory factor [18]. The mechanism of occurrence of arthropathy is multifactorial; inflammation of the synovial membrane that is induced by hemosiderin and other agents in blood leads to inflammatory joint disease and also cartilage destruction because of the direct corrosive effect of blood, which leads to degenerative disease [19]. Chronic hemophilic arthropathy may affect a significant number of joints in children with severe hemophilia. Knee was the most common target joint in our study cases (28.6% of patients). This coincides with a study by Hassab et al. [20] on hemophilic patients where knee was the most commonly affected joint (83.3%). In our study, patient’s age had a significant effect on joint score. With age, the joint was exposed to more frequent hemarthrosis and thus more joint damage. Various studies illustrated the effect of age of the patient on HJHS [21],[22].

Rest, ice fomentation, compression, and elevation are generally suggested as an adjunct to factor replacement therapy during acute joint bleeding, [5],[6], but the benefits of these measures are not well established. Ice may decrease pain, inflammation, and tissue damage; it also slows blood flow, platelet function, and enzymatic reactions, including conversion of prothrombin to thrombin [5],[23]. Our study revealed that there is a nonsignificantly lower HJHS as regards applying conservative managements in the form of ice, rest, elevation, and compression. This finding may indicate the limited effect of these measures on reducing joint damage, although it could be used to relieve pain. This result was consistent with that of Hubbard and Denegar who reported that using ice or combined ice and compression after minor knee surgery had no effect on the range of motion (ROM) and girth. However, they found that ice, compression, and a placebo injection reduced pain more than a placebo injection alone [23]. In contrast, Basur and colleagues found that cryotherapy reduces edema, pain, disability, and recovery time in acute ankle sprain [24],[25].

Physiotherapy is an essential adjunct therapy in hemophilia patients with acute and chronic joint bleeding [26]. Hydrotherapy is particularly recommended for patients with multiple joint arthropathies, who find land-based functional stretching and strengthening exercise difficult [27]. Hydrotherapy not only reduces pain but also decreases bleeding frequency and instability in target joints and improves ROM and muscle girth [28]. Isometric and isotonic exercise and transcutaneous electrical nerve stimulations are other modalities of physiotherapy used both acutely and chronically in the rehabilitation of hemophilia patients following hemarthrosis [29]. In children with severe hemophilia who are on episodic treatment, moderate-intensity exercise has a positive effect on homeostatic system and it may be safe and beneficial for those patients [30]; our study revealed that there is a statistically significant difference with a P-value of 0.04 with regard to the level of total joint score, with a negative effect of physiotherapy on total joint score. The multivariate logistic regression model analysis was conducted to explore the explanatory power of different risk factors on total joint score, and it illustrates that there were statistically significant predictors to physiotherapy, with a P-value of 0.006, which illustrates the beneficial effect of physiotherapy on improvement of joint score. This was consistent with a study by Mazloum et al. [31] who concluded that aquatic exercise therapy can increase knee joint ROM in hemophilic patients. Effects of hydrostatic pressure on the body during the immersion cause centralization of peripheral fluid. This results in various physiological responses such as increasing cardiac output and decreasing peripheral resistance [32]. Reducing edema, inflammation, and improvement in contractile tissues activity are the results of this process [31]. In addition, a study by Mulvany et al. [33] reported that exercise therapy supervised by a physical therapist can increase ROM in affected joints.

Before the routine use of recombinant factor VIII replacement therapy and in localities where there was insufficient availability of it, pooled plasma was the only therapeutic option, and thus many patients had been infected with HCV. Although liver is the main site of affection by HCV, extrahepatic involvement − such as the musculoskeletal system in the form of arthralgia and arthritis − has been reported [34]. The mechanism of HCV-induced arthritis is indistinct; it is thought to be a local inflammatory response that is caused by direct viral invasion or deposition of cryoglobulin-induced immune complexes in synovial fluid. In this study, HCV seropositivity was detected in 9.5% of the studied cases, but no significant effect on HJHS could be elicited.

Parental education can affect their children’s health through different ways. It can increase the ability to gain and process the information. High education level may give access to more skilled work and thus higher income, which can be reflected on health. Higher education has a role in increasing risk aversion and self-caring [35]. However, in our study, no significant differences in HJHS were found as regards the level of parental education. The presence of effective sessions of health education about the nature of the disease and its management may be the cause, as it can raise the awareness even in parents with low level of education. Health instructions can improve health practice in adolescent patients with hemophilia [36].

  Conclusion Top

Performing physiotherapy can improve joint health among hemophilia patients who are on episodic treatment regimen. Physiotherapy should be encouraged as an adjunctive treatment to replacement therapy. Conservative measures (ice, rest, compression, and elevation) alone cannot preserve joint health; however, they must be recommended, and the patient must be educated to relieve pain and swelling at the time of active bleeding. Effective health education can overcome the predictive health differences as regards parental level of education.

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Conflicts of interest

There are no conflicts of interest.

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  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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