Abstract
Purpose
Hemophilia is a hereditary coagulation disorder characterized by acute hemorrhages into the musculoskeletal system, leading eventually to arthropathy and disability. Chronic inflammation of the synovial membrane arises as a result of frequent joint hemorrhage. Proteolytic enzymes in the blood and cartilage cause deterioration after that, and joint space narrows. Chronic hemophilic arthropathy develops as a result of these unfavorable developments, which occur more quickly, especially in the target joints. Balance is a process that allows us to maintain our orientation in three-dimensional space while also regulating our body posture to avoid falling. After the central nervous system evaluates deep stimuli from sensory, visual, and auditory receptors, movement of the corresponding muscle groups is delivered.
Methods
The goal of this study was to investigate how impairment to deep sensory receptors (proprioception) in the arthropathic joint structure affected hemophiliacs’ balance. The study comprised 34 patients with hemophilic arthropathy, and 34 age and weight matched healthy volunteers.
Results
When balance tests of patients with hemophilic arthropathy were compared to healthy controls, hemophiliacs had a greater risk of falling. As the degree of arthropathy increased, so did the risk of falling and balance test values in individuals with hemophilic arthropathy.
Conclusions
Treatment and coagulation factor prophylaxis to prevent the onset of arthropathy will improve patients’ quality of life and reduce morbidity associated with frequent falls and bleeding.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12288-022-01526-0.
Keywords: Hemophilia, Hemophilic arthropathy, Balance, Static balance, Dynamic balance, Functional balance
Introduction
The ability of the body to retain its center of gravity in the face of gravity and external forces is known as balance. Balance is achieved when all visual, vestibular, and proprioceptive sensations, including those from joints, are fully functional. Balance of a person can be achieved through evaluation and integration of the stimuli in the central nervous system [1, 2]. Repeated intra-articular bleedings in persons with hemophilia (PWH) cause hemophilic arthropathy [3]. Damage to the deep sensory afferent receptors (proprioception) in the joint region may result in loss of balance in these patients, in addition to the consequences on shape and function [4, 5].
There are two types of balance: static and dynamic. Dynamic balance is the ability of the body to move its position, posture, and center of gravity appropriately, whereas static balance is the ability of a person to maintain his or her posture. A variety of tests, ranging from simple to complicated measurements with various digital systems, can be used to determine the balance. Because there is no single test that can assess all of the components of balance, distinct aspects of postural control can be assessed using a series of tests. Studies on the influence of hemophilic arthropathy on balance and its role in providing postural equilibrium are sparse in English literature [2]. The goal of this study was to compare the effects of impairment to deep sensory receptors in hemophiliacs’ arthropathic joints on balance function to those in healthy participants.
Methods
This controlled cross-sectional study comprised of patients diagnosed with hemophilia and over 10 years of age who are followed up at our Hemophilia Care Center. Hemophiliacs with a single target joint in their lower extremities (Hemophilic arthropathy group) were included in the trial (HAG). Those who had active joint bleeding in the previous two weeks were ruled out. The control group (CG) consisted of healthy volunteer boys who were stratified according to their age and body mass index (BMI) of the HAG patients. Boys who have had an acute or chronic condition, or who have experienced trauma in the last two weeks, have been excluded from the trial.
All subjects had a thorough medical history taken and a physical examination completed. According to their FVIII/IX levels, patients were classified as having severe (1%), moderate (1–5%), or mild (5–40%) hemophilia. The Gilbert score (GS) [6] has been used to assess arthropathic joints. The effect of the target joint and dominant extremity on balance has been documented to explore the effect of being left or right-handed. The same radiologist examined the patients’ arthritic joints using a direct radiograph. The patients’ most recent direct radiographs were rated using the radiologic assessment scale devised by Pettersson et al. [7]. The study was reviewed and approved by the local ethics committee, (2017 − 101). Written informed consent has been obtained from the participants and parents.
A series of tests were utilized to assess various aspects of balance. The dynamic variant of the balance was evaluated using the Functional Reach Test (FRT). Then, the result was compared to the reference values [8, 9]. In statistical analysis, the ratio [(FRT/Height)x100] was employed to eliminate the effect of variance in height. Functional balance and the risk of falling are assessed using the pediatric Berg Balance Scale and Timed Up and Go Tests (TU>). A total of 14 items from the Pediatric Berg Balance Scale were used [1]. Each participant was repeated three times Timed Up and Go Test, and the median value was used in the analysis [9]. In both HAG and CG, static balance was assessed using a device (TechnoBody S.R.1. Dalmine, 24,044 Bergamo, Italy) [10]. The Technobody isokinetic balance device was created to research people’s postural balance components. The device is composed of a movable platform and a computer with the Prokin Software System (core program module testing dynamic, static, and proprioceptive status). Patients are given different levels of resistance depending on their weight. When switching from static to dynamic measurement, the platform is moved by air-driven piston bases. After getting into the proper position on the equipment, the boys were told not to use their arms for support throughout the measurement to avoid the upper extremities affecting balance. After a two-minute practice period, the test was administered. During the test, which lasted 30 s, the boys were asked to hold their positions on a movable ground while the shapes on a screen changed. They were subsequently instructed to maintain their positions on the midline and then to balance with their eyes closed. The center of pressure (COP) is the location on the body where the pressure is increased, and it is defined by two axes (X-axis; anteroposterior and Y-axis; mediolateral). The higher the rate of oscillation in COP readings shows the worse the static balancing situation.
Statistical Analysis
Statistical analysis of the data was performed by using SPSS 15 package software (SPSS Inc Chicago IL, USA). Normality of the distribution of variables was analyzed with Shapiro-Wilk test. Parametric variables are expressed as mean ± SD, and non-parametric variables as median (minimum-maximum) values. Chi-squared was used for comparison of categorical variables. Independent Sample t test, and Mann Whitney U test was used for comparison of the continuous variables in two independent groups according to data normally distributed or not. Comparison of more than three dependent continuous variables was made with Kruskal Wallis test. Pearson test was used for the parametric variables, and Spearman test was used for the non-parametric variables for determination of the correlation. If p value < 0.05, it was considered as statistically significant.
Results
The study comprised 34 patients with hemophilic arthropathy and 34 healthy boys who were age and weight-matched. All of the participants were male. Patients in HAG had a mean age of 15.6 ± 3.3 years and 19.2 ± 1 kg/m2, whereas those in CG had a mean age of 15.7 ± 3.3 years and 19.8 ± 2 kg/m2, respectively. In terms of age and BMI, there was no statistically significant difference between the groups (p > 0.05). In HAG, 27 (80%) of the 34 patients had hemophilia A, whereas 7 (20%) had hemophilia B. According to the baseline factor levels, 33 individuals (97%) had severe hemophilia, and one (3%) had moderate hemophilia. Three of the 27 patients with hemophilia A (8.8%) had inhibitors, whereas none of the individuals with hemophilia B had inhibitors. All of the patients had been on prophylactic therapy for at least a year. The patients were mostly right-handed [28 (82.3%) right-handed, 6 (17.6%) left-handed]. Although the majority of our patients were right-handed (83%) there was no difference in the involvement of left- and right-sided joints (p > 0.05). At a median of 21.1 (14–28) months ago, six (17.6%) patients had had radioactive synovectomy (all of the joints were knee). Pettersson and Gilbert scores of the HAG are presented in Tables 1 and 2.
Table 1.
Gilbert scores of the patients by involved joint
|
All patients [n = 34] Mild Moderate Severe |
11 (32.4%) 16 (47.1%) 7 (20.6%) |
|
Knee Joint [n = 27] Mild Moderate Severe |
8 (29.6%) 12 (44.4%) 7 (25.9%) |
|
Ankle Joint [n = 7] Mild Moderate Severe |
3 (42.8%) 4 (57.1%) 0 |
Table 2.
Pettersson Scores of the Patients
| Pettersson Scores [median (range)] | |
|---|---|
| All patients [n = 34] | 8.1 (3–12) |
|
Patients by GS Severe [n = 7] Moderate [n = 16] Mild [n = 11] |
10.5 (8–12) 8.3 (6–11) 6.2 (3–10) |
GS: Gilbert score
In the HAG, the median distance measured in FRT was 34.5 (19–40) cm, while in the CG, it was 34.6 (24–46) cm. There was no statistically significant difference between the two groups (p > 0.05). A positive association was identified between age and FRT scores in both groups, indicating that FRT scores increase with age. There was no statistically significant difference between those who had inhibitors and those who did not, or between those who had hemophilia A or B (p > 0.05). The HAG had a significantly lower pediatric Berg Balance score [median 51.5 (range, 49–56)] than the CG [median 55 (range, 52–56)] (p = 0.006). TU> timings were substantially longer in the HAG [median 9.7 s (range, 8.6–12.6)] than in the CG [median 9.2 s (range, 8.5–11.9)] (p = 0.0064), confirming these findings. In terms of the Pediatric Berg Balance Test and TU>, the presence of inhibitor, type of hemophilia (A or B), and age did not differ between the two groups (p > 0.05). Patients with severe arthropathy had considerably lower Berg Balance scores (p < 0.001) and significantly longer TU> times than those with mild and moderate arthropathy defined by GS (p < 0.001) (Fig. 1).
Fig. 1.
(a) Comparison of Pediatric Berg Balance scores by severity of arthropathy (Gilbert score) (b) Comparison of TU> times by severity of arthropathy (Gilbert score)
Isokinetic Balance Test
Patients’ data were analyzed with both open and closed eyes. When the HAG’s open eyes data was compared to the CG’s, considerably larger oscillations in the anteroposterior axis (COP X) measurement were found (p = 0.013). Measurements on the mediolateral axis (COP Y) in HAG showed higher oscillations than those in CG, while the difference was statistically insignificant. The HAG group also had higher oscillations in the anteroposterior and mediolateral axes when the eyes were closed, but the difference was not statistically significant. There was no significant correlation between disease severity and joint scores, or the presence of inhibitors. Both with open and closed eyes, the speed of front back oscillations was significantly higher in the HAG (p = 0.002 and p = 0.026, respectively). There was no significant difference in mediolateral oscillation whether the eyes were open or closed. There was also no significant correlation between the speed of anteroposterior oscillations and the severity of the disease or joint scores (p > 0.05). When the ellipse area and perimeter width that was drawn by the software according to the oscillations from COP were compared, a significantly wider area has been obtained in the HAG compared CG both with open and closed eyes (Table 3). These findings were not correlated with disease severity or joint scores.
Table 3.
Comparison of the balance tests results
| HAG (n = 34) median (range) |
CG (n = 34) median (range) |
p | |
|---|---|---|---|
| Pediatric Berg Balance score | 51.5 (52–56) | 55 (52–56) | 0.006 |
| TU> (sec) | 9.7 (8.6–12.6) | 9.2 (8.5–11.9) | 0.0064 |
| FRT score | 34.5 (19–40) | 34.6 (24–46) | 0.271 |
| Isokinetic balance device measurements | |||
|
COP X (OE) COP X (CE) COP Y (OE) COP Y (CE) |
-0.78 ± 1.99 -0.33 ± 9.77 -2 (-11-1) -5 (-18-20) |
0 (-5-3) 0 (-9-18) -1 (-2-6) -5 (-18-2) |
0.013 0.478 0.306 0.880 |
|
sFB deviation (OE) sFB deviation (CE) sML deviation (OE) sML deviation (CE) |
7 (3–17) 8.48 ± 3.66 4 (2–14) 4 (2–18) |
5 (3–11) 5 (3–16) 3.5 (2–14) 4 (2–18) |
0.013 0.022 0.246 0.486 |
|
aFB speed (OE) aFB speed (CE) aML speed (OE) aML speed (CE) |
12.90 ± 4.31 15.24 ± 5.55 7 (5–19) 8 (5–22) |
9 (6–25) 12 (7–22) 8 (5–19) 8.23 ± 2.11 |
0.002 0.029 0.840 0.718 |
|
Ellipse area (OE) Ellipse area (CE) Perimeter width (OE) Perimeter width (CE) |
547 (126–1708) 632 (98-3976) 533.5 ± 191.3 558 (325–1359) |
242 (150–1455) 317 (98-1454) 405 (279–1088) 481 (253–902) |
0.010 0.012 0.012 0.036 |
aFB, aML speed: Average front-back, mediolateral speed; CG: Control group; COP X, Y: Center of Pressure X, Y; FRT: Functional Reach Test; HAG: Hemophilic arthropathy group; OE: Open Eyes; CE: Closed Eyes; sFB, sML deviation: Standart front-back, medio-lateral deviation; TU>: Time Up and Go Test
Discussion
Deep sensory receptor pathologies and afferent sensory conduction impairment in an arthropathic joint might create postural instability in PWH and make them more likely to fall [8]. In this study, a set of balance tests were administered to children with hemophilic arthropathy to investigate the impact of lower extremity arthropathies on balance, and they were compared to age and weight-matched healthy peers. Our findings revealed that PWH’s balance is disturbed, which could lead to more falls and accidents.
One of the tests used to determine the functional balance in our study, the Pediatric Berg Balance Scale, revealed significantly lower scores in HAG compared to CG. Furthermore, patients with severe arthropathy obtained lower scores on this test. An adult study comprised of 147 PWH evaluated the incidence and risk of falling revealed that the number of falls was increased in those with frequent intra-articular bleedings and a higher number of target joints. Besides, almost half of the patients had fallen more than once within the previous year [11]. TU> times were significantly longer in patients who had joints with higher GSs in our study. Baumgardner et al. found no significant differences in TU> between 88 adults with hemophilic arthropathy and healthy controls [12]. TU> times, likewise in our study, tended to be longer among individuals with lower joint scores. These findings, along with recent research, suggest that increasing articular damage causes functional components of balance to be disrupted [13, 14]. Due to a loss of balance, arthropathy appears to be a risk factor for falls and subsequent bleeding. The FRT is used to measure the dynamic component of balance. An adult study revealed that FRT scores were statistically lower in patients with hemophilic arthropathy compared to controls [14]. However, we were unable to detect such a difference in our study, which could be owing to the small sample size. To assess dynamic balance in children with hemophilic arthropathy, further studies with larger patient groups is required.
Various devices can be used to measure the static component of postural balance. Our findings revealed that HAG both opened and closed eyes had higher anteroposterior axis oscillations and faster front back oscillations. Impaired balance in our patients could be caused by a loss of proprioception in the deteriorated joint. Tat et al. recently investigated 21 PWH between the ages of 6 and 18 using the same instrument as ours and found that PWH had considerably greater mediolateral oscillations [15]. The clinical score of the lower limb joints was moderately correlated with these findings. An adult study tested 20 PWH with frequent joint bleeding (joints were not defined) for postural balance and compared to healthy persons [14]. COP oscillations were found to be higher in PWH measured using a balance equipment (NeuroCom Balance Master). The importance of joint health in maintaining balance is also supported by this research. It is generally established that PWH on prophylaxis had a decreased incidence of joint bleeds and arthropathy.
It is well known that a lower incidence of joint bleeds and arthropathy occurs in PWH on prophylaxis. However, in developing counties, it was reported that most of the PWH was receiving on-demand treatment and 84% had target joint resulting that 70% of them having orthopedic disabilities [16]. Boccalandro et al. investigated static balance in children with hemophilia using the BioPostural System (AXA Srl, Vimercate, Italy) and found no significant relationship between hemophilia joint health score (HJHS) and balance [17]. However, the majority of the patients in that study (71%) had an HJHS of zero, whereas the remaining ten patients had a target joint with a median HJHS of three (range, 2–8). They concluded that if patients had lower joint scores as a result of good physical activities and prophylaxis at a young age, their postural balance would be similar to that of healthy people. In another study, static balance parameters were assessed at two-time points: before and after a 6-week exercise program conducted at home by individuals with hemophilic arthropathy [18]. While frontback oscillation score was higher likewise our study, a significant decrease has been obtained with a proper exercise program. Regular exercise regimens are well known for strengthening patients’ joints and surrounding muscular tissues, as well as assisting them in achieving a more upright posture and static balance. These findings highlight the need of physical treatment, regular exercise, and factor prophylaxis in maintaining good balance and avoiding falls and accidents.
In conclusion, we found significant impairments in functional and static components of balance in children with hemophilic arthropathy compared to healthy peers, and the impairment was related to the severity of the arthropathy. Preventing impairment in balance and destructive alterations to joints requires regular prophylaxis, early initiation of physical therapy, and exercise programs. These measures will help to reduce the risk of falling and bleeding.
Electronic Supplementary Material
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Funding
No funding was received for conducting this study.
Statements and Declerations
Competing Interest
The authors have no relevant financial or non-financial interests to disclose.
Ethics Approval
Approval was obtained from the ethics committee of University of Health Sciences, Ankara Child Health and Diseases Hematology and Oncology Training and Research Hospital (2017 − 101). The procedures used in this study adhere to the tenets of the Declaration of Helsinki.
Consent to Participate
Written informed consent was obtained from the parents.
Conflict of Interest and Source of Funding
None declared.
Footnotes
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