Hemophilia is a chronic congenital blood disease, whose main clinical manifestations are joint (hemarthrosis) and muscle (hematoma) bleeding, which occurs either spontaneously or because of trauma. Successive hemarthrosis recurrence in the same joint (target joint) causes progressive joint deterioration, known as hemophilic arthropathy. Currently, prophylactic treatment in the form of periodic infusion of FVIII/FIX has managed to reduce the frequency of bleeding in children with hemophilia, preventing and minimizing the incidence and prevalence of disabling physical effects.1 , 2 However, prophylaxis alone is unable to prevent associated bleeding and joint damage, and can affect the quality of life (QoL) of children.3
QoL is a widely studied variable in people with hemophilia as a measure for evaluating medical and therapeutic progress.4 , 5 QoL studies in general population adults have been conducted since the 70s; however, instruments to measure this variable were not developed until the 80s.6 , 7 Rosendaal et al8 were the first authors to point out the importance of QoL in people with hemophilia, noting that it did not differ from that of the general population. Subsequent studies have underlined how variables such as the type of treatment9 , 10 and the condition of the joint11 , 12 may influence QoL. Studies on QoL during childhood and adolescence were first conducted in the 90s.13–15 Liesner et al16 were the first authors to consider the importance of QoL in pediatric and young population with hemophilia.17 , 18 Initially, child QoL was assessed using the information provided by the parents, with the risk of bias in their perceptions. The assessment of QoL in childhood and adolescence should take into account the changes in the physical, emotional, and social development, as well as the child's ability to understand them. In chronic diseases, children have more difficulties and are more vulnerable to the effect of the disease, becoming physically and psychologically dependent on the family. Several studies have observed how age correlates directly with a better score on the physical and psychosocial dimensions of children with hemophilia.19 , 20
The new treatment options and prophylactic schedules enable children with hemophilia to enjoy a similar childhood to that of their peers,11 , 21 being able to participate in social activities and sports activity needed to prevent bleeding and for their own wellness.
Until the 70s, physical and sports activities were not recommended in people with hemophilia because of the risk of bleeding. This has now changed, with sports activities considered beneficial and forming part of treatment.5 , 22 Several studies have evaluated how conducting individualized and safe programs23 , 24 of physical activity and sport have a positive effect on the perception of QoL for adults and children with hemophilia.10 , 25–28
Noncompetitive sports activity in hemophilia has not been considered until quite recently as beneficial. Now health professionals consider sport beneficial for physical aspects26 , 29 and for improving social and psychological aspects, promoting a better overall health.25 , 29 , 30 One of the variables that has most influenced the improvement in QoL is implementation of prophylaxis,1 , 3 which reduces and prevents bleeding, and therefore prevents the progressive joint deterioration. The World Federation of Haemophilia22 , 31 and national associations32 , 33 recommended prophylaxis; however, these are not generally applied in adult patients or in countries with scarce resources.
The aim of this study is to assess the effects of noncompetitive sports activity on the QoL of children with hemophilia compared with a control group of children without hemophilia.
MATERIALS AND METHODS
This was an observational study in children with hemophilia and in healthy peers.
Selection and Recruitment of the Sample
The study was conducted during the months of July 2014 and January 2015. Patients with hemophilia were recruited by the Spanish Federation of Hemophilia from different regions throughout Spain. The control group, consisting of 51 children, was recruited from a primary school center. We evaluated 53 children with hemophilia aged 7 to 13 years who stayed at the youth hostel.
Exclusion criteria were patients diagnosed with other congenital coagulopathies (eg, von Willebrand disease), patients with hemarthrosis in the previous month, and patients with difficulty understanding the indications of evaluators or with poor reading comprehension.
The study was approved by the Ethics Committee of the University of Valencia (register number H1433514767513). Once the parents or legal guardians of the participants had been informed by the researchers of the study objectives, they signed the informed consent.
The study was registered in the International Register of Clinical Research (NCT02198430).
To assess the QoL and joint health, we used the Spanish versions of the following questionnaires:
- Haemophilia Joint Health Score 2.1 (HJHS).34 The scale developed by the International Prophylaxis Study Group assesses joint health in patients with hemophilia. It consists of 8 dimensions: swelling, muscular atrophy, crepitation, range of motion, joint pain, strength, motion, and axial alignment.
- Child health profile (Childhood Health and Illness Perception; CHIP-CE).35 The generic scale developed to evaluate the perception of QoL in childhood consists of 5 dimensions: satisfaction (assesses satisfaction with overall health and self-esteem), resistance (appreciates the family involvement, problem solving, physical activity, and health and safety at home), wellness (appreciates physical and emotional well-being, and activity limitation), risk (evaluates individual risk, the threat of achievements, and influence of their peers), and function (assesses the academic and work performance). The score ranges from 0 (poor QoL) to 100 points (good perception of QoL).
The clinical data of patients with hemophilia were obtained, including the type and severity of hemophilia, the type of treatment they received at the time (prophylaxis or on demand), the presence of antibodies to FVIII/FIX (inhibitors), and the establishment of a central venous access. Also, anthropometric variables (height, weight, and body mass index), age, and sport for all subjects included in the sample were evaluated.
Statistical analysis was performed using the SPSS 19.0 statistical package for Windows (IBM Corporation, Somers, New York). A descriptive analysis of the subjects in both groups of the study was conducted. We used the t test to analyze differences depending on the group, and through the Pearson correlation coefficient we observed correlations between the study variables. A multivariate cluster analysis was conducted using the K-means method, for obtaining empirical groups. We determined a level of 95% to estimate the confidence interval.
One hundred four subjects participated in our study. Fifty-three were in the group with hemophilia and 51 to the group without hemophilia. The average age of the total sample was 10 years (range 7-13 years). The average weight was 39.15 kg and the average height was 148.59 cm. One significantly overweight child, with a weight of 100.9 kg, exceeded the range of this variable. Regarding the body mass index of children enrolled in the study, the average was 18.19 (normal range). On average, in the group of patients with hemophilia, it was slightly lower (17.84) than the group without hemophilia (18.55). Sport was carried out 1.29 days per week on average. The sports played by children with hemophilia were swimming, cycling, tennis, and football. Both groups were similar at baseline, and with no significant differences. Table 1 includes the main descriptive characteristics of the groups.
The diagnosis of hemophilia A was the most prevalent at 92.5%, the severe phenotype being the most common (73.6%), and most of the children were following a prophylactic treatment (81.1%). Only 7.5% of children had developed inhibitors, and most did not need central venous access (94.3%) to administer the factor.
Scores on the HJHS scale regarding joint health are presented, along with the clinical characteristics in Table 2.
Student t Test and Correlation Analysis
Table 3 includes the scores on the scale of QoL in both groups. There were no significant differences in any of the subscales, including children with and without hemophilia.
There were significant differences in QoL, depending on the sport played, within the group of patients with hemophilia in the subscale of satisfaction with health status in favor of individuals who played sports, versus those who did not (F = 7.258; P = .010).
The analysis of correlations between QoL variables and the scale of joint health in patients with hemophilia had significant negative correlations between different types of QoL subscales: satisfaction with affected knee (F = −0.369; P = .007) and right elbow (F = −0.324: P = .018), and wellness with impaired left elbow (F = −0.321; P = .019).
This type of multivariate analysis allows us to group the different cases studied depending on the degree of similarity and dissimilarity among them. The goal is to classify subjects according to this criterion and thus obtain empirical groupings or patterns of response to the set of variables studied.
We performed a cluster analysis of patients with hemophilia (n = 53) using the K-means method. There were 3 patterns of response, using the following variables: the subscales of quality of life and joint condition of our patients, using the HJHS scale. The sport variable was also included. Table 4 includes the results of the cluster analysis.
The first grouping consists of 37 patients (69.8% of the sample), with minor joint impairment, according to the HJHS scale, located on the right ankle. They play sport 2 days a week and their QoL has the highest scores on the variables of wellness, risk behavior and function.
The second group consists of 4 patients (7.5% of the sample). Unlike the preceding group, the left ankle is the most affected, and they play sport 3 days a week. Regarding their perception of QoL, the 4 subjects in this group had the highest scores on the resistance subscale and the lowest scores on those for wellness and risk behaviors.
The third group consisted of 12 children with hemophilia (22.6% of the sample). Unlike the other groups, these subjects were affected in all joints except the left knee, reducing sports activity to 1 day a week. Satisfaction with health, strength, and function were the variables with the lowest QoL scores.
We observed homogeneity between the group of children with hemophilia compared with the children without hemophilia in the descriptive variables. One important variable is weight. Being overweight and obese are risk factors in the development and progression of joint36 problems. In children with hemophilia it is essential to maintain weight within a normal range to avoid compromising the condition of the joints, especially weight-bearing joints (knees and ankles).37 The children in our study, as in the study conducted by Iorio et al,38 had a healthy weight, which favors a lower risk of bleeding and joint problems. With our relatively large sample size with patients from across Spain, we established that patients in our sample are not overweight, contrary to what has been described by Hofstede et al39 in a prospective study conducted between 1992 and 2001.40 QoL in children with hemophilia was not only affected by the clinical aspects of the disease or by the difficulties of treatment. Depriving children and adolescents of being physically active can affect the development of their personal identity.24 , 41 Psychosocial variables seem to affect the QoL positively or negatively, especially for children. Some studies have indicated how psychosocial variables, though not statistically significant, may have great clinical relevance.42 , 43
We observed that the QoL of children with hemophilia is similar to that found for children without hemophilia. These results are in agreement with previous studies,25 , 30 in which the relevant role of the introduction of prophylactic treatments is highlighted.17 Sixty-two percent of our children are physically active and of these 56% engage in a sports activity regularly, 2 to 3 days a week, resulting in a significant correlation of sport with the perception of health satisfaction and self-esteem. Also, negative correlations were found between the perception of health satisfaction and wellness, and the clinical assessment of joint health as measured by the HJHS scale.
Our results agree with those obtained in the multicenter study by Khair et al,28 who found that sport improved the QoL of children with hemophilia, perceiving themselves as less limited and giving them a better self-image. Other studies27 have reported that children with hemophilia consider their daily sports activity as routine. Similarly, our results coincide with those obtained by other authors, who found no clinical differences between patients who play sports and those who do not in relation to the physical risk,44 , 45 or a higher frequency of hemarthrosis.46
Our result supports that exercise improves the physical aspects of the children with hemophilia as well as the psychosocial aspects. Their better social interaction assists them in creating a better image of themselves and the ability to control their disease.25 , 42 , 47 Therefore, noncompetitive sports activity (days per week) has to be monitored by individualized treatment schedules and periodic evaluations of the joint condition.26 , 48 , 49
Cluster analysis shows 3 response patterns that characterize children with hemophilia on the basis of their perception of Qol, joint health, and practice of sport. The first group, comprising 70% of children with hemophilia, has a good perception of Qol and risk control, and they do not feel different from their healthy peers in terms of their expectations and achievements. Similarly, they play sports regularly and have a minimum joint deterioration (right ankle). The second group, composed of only 7% of the sample, is characterized by playing sport more often, being exposed to greater risks. But their perception of Qol is “quality-adjusted”, their joints are minimally affected (left ankle), and they have family and own resources for coping with the disease.
The third and last group, comprising 23% of children with hemophilia, has a poor perception of QoL, many limitations because of their disease, fewer resources to face the difficulties, low self-esteem, and low expectations of achievement compared with their peers. They minimally play sports and their joints are more affected. What we observed in the third group is similar to the results obtained in patients recruited by Gringeri et al,30 who had a poorer QoL in relation to a higher frequency of major bleeding and physical limitations.
According to the cluster analysis, 77% of children with hemophilia carried out a physical or sporting activity regularly, perceiving a satisfactory QoL and having a good overall joint condition. These results support the relationship between physical exercise and good joint health, and a better QoL. The remaining 23%, who did not perform any type of physical activity, presented a poorer QoL and more affected joints. Therefore, these patients should receive physiotherapy and psychosocial interventions, as well as guidance for the development of controlled sports activities, commensurate with their physical condition.
Professionals should guide the child with hemophilia to a perception of competence with regard to the disease. This includes support, resources, and an environment that encourages their participation in activities favoring their integration and the control of their disease.
The sample size is a limitation of our study. Failure to conduct an intervention with children with hemophilia during their stay at the youth hostel does not allow us to test its potential influence on the study results. Another limitation of the study is the provenance of subjects included in the study. Although children with hemophilia were from all regions of Spain, children without hemophilia could not be recruited from those same regions (they were all from 1 community).
Relevance to Clinical Practice
The results of this study allow us to identify and group children with hemophilia on the basis of 3 variables. By early identification, it may be possible to intervene at an early stage, thereby improving their perception of QoL.
Sports activity in children with hemophilia is associated with a better QoL and improved joint health. It is also associated with better psychosocial wellness similar to that enjoyed by all children.
It is essential that the disease does not affect the welfare and development of children with hemophilia. It is therefore essential to inform and educate parents from the moment the disease is diagnosed.
They must be made aware that, in addition to prophylactic treatment, exercise can help to maintain joint health and prevent hemophilic arthropathy.
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