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 Table of Contents  
Year : 2021  |  Volume : 8  |  Issue : 3  |  Page : 187-191

Responsiveness to hemophilia joint health score and functional independence score in patients with hemophilia with intermittent factor support and physiotherapy

1 Department of Clinical Haematology, Haemato-Oncology and Bone Marrow (Stem cell) Transplantation, Christian Medical College, Ludhiana, Punjab, India
2 Department of Physiotherapy, Christian Medical College, Ludhiana, Punjab, India
3 Department of PMR, Christian Medical College, Ludhiana, Punjab, India
4 Department of Orthopaedics, Christian Medical College, Ludhiana, Punjab, India

Date of Submission27-Sep-2020
Date of Acceptance29-Jul-2021
Date of Web Publication04-Mar-2022

Correspondence Address:
M Joseph John
Department of Clinical Haematology, Haemato-Oncology and Bone Marrow (Stem Cell) Transplantation, Christian Medical College and Hospital, Ludhiana - 141 008, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cjhr.cjhr_138_20

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Introduction: Hemophilia is a hereditary bleeding disorder with significant consequences involving the joints, leading to debilitating functions. Prophylactic replacement therapy is limited in lower-middle-income countries, and often it is the episodic or intermittent factor replacement which is feasible. Although many tools are available to evaluate the assessment of joints at the time of initial contact, its utility in response evaluation to intervention is limited. Materials and Methods: In this quasi-experimental study, we compared the Hemophilia Joint Health Score (HJHS) and Functional Independence Score in Hemophilia (FISH) scores pre and postphysiotherapy with intermittent factor support. Results: Forty-eight patients with hemophilia (PwH) were screened, and 18 PwH consented and completed the treatment protocol. The mean duration of physiotherapy was 11 days, with an average total factor consumption of 120 U/Kg. The pre and postphysiotherapy HJHS was 40 ± 18.8 and 19.5 ± 11.9 with a standardized response mean (SRM) of −2.41 (95% confidence interval [CI] −3.25–−1.53) and FISH, 16.89 ± 3.44 and 22.33 ± 3.36 with SRM of 1.78 (195% CI.29–2.23). Both the SRMs were statistically significant (both the P values were 0.000). Conclusion: This study highlights the utility of HJHS and FISH in assessing responsiveness to intermittent prophylaxis and physiotherapy.

Keywords: Factor VIII, Functional Independence Score in Hemophilia, hemophilia, Hemophilia Joint Health Score, intermittent, responsiveness

How to cite this article:
Singh R, Dinakaran M, Vandhiyadevan G D, Mathangi S, Pandey RA, John M J. Responsiveness to hemophilia joint health score and functional independence score in patients with hemophilia with intermittent factor support and physiotherapy. CHRISMED J Health Res 2021;8:187-91

How to cite this URL:
Singh R, Dinakaran M, Vandhiyadevan G D, Mathangi S, Pandey RA, John M J. Responsiveness to hemophilia joint health score and functional independence score in patients with hemophilia with intermittent factor support and physiotherapy. CHRISMED J Health Res [serial online] 2021 [cited 2022 Jul 7];8:187-91. Available from: https://www.cjhr.org/text.asp?2021/8/3/187/339041

  Introduction Top

Hemophilia is an X-linked recessive hereditary bleeding disorder which occurs due to deficiency of coagulation factors VIII and IX in the body. Their incidence ranges from 8 to 20 and 1–8 for every 100,000 male patients, respectively, depending on the geographical area.[1],[2]

Hemophilia presents as recurrent bleeding episodes that occur spontaneously or after any trauma or surgical procedure. The most commonly affected joints are the knee, ankle, and elbow.[3],[4] Because of repeated and progressive bleeding episodes referred to as hemarthrosis, changes such as synovial hypertrophy occurs in the joint, causing damages to the joint structures. Recurrent bleeding results in degenerative changes that lead to bone loss resulting in decreased functioning of the affected joints, known as hemophilic arthropathy.[5]

The development of hemophilic arthropathy is the last phase of joint damage which clinically presents as severe chronic pain, reduction in the range of movement of the affected joints, reduced muscle mass, and decreased proprioception. These changes usually set in the first 10 years of life because of the susceptibility of the joint ligament to the wear and tear brought about by the iron in the blood.[6]

The best treatment to prevent the recurrent hemarthrosis and hemophilic arthropathy is the standard infusion of FVIII or FIX concentrates in the form of continuous prophylactic treatment.[7],[8] Treatment of these bleeding episodes in the form of on-demand treatment or intermittent treatment may delay the occurrence of long-term complications, however, do not prevent them.[9],[10] As continuous prophylaxis may not be an affordable option in the majority of patients in developing countries, physiotherapy is another simple means to improve quality of life by not only improving healing but also decreasing the incidence of bleeds in hemophilic patients. The two main objectives of physiotherapy in patients with hemophilia (PwH) are to restore the functionality, maintain the range of motion, and to improve muscle strength and proprioception.[11]

A recent global survey has shown that India has one of the lowest factor usages and the per capita use of FVIII concentrates in India is 0.23 IU as compared to a global average of 2.17 IU.[12] In Punjab, only 1% of patients are on continuous prophylaxis, and more than 80% of patients with severe hemophilia have joint abnormalities.[13] Despite having the largest number of global persons with hemophilia, the diminished per capita use of treatment product illustrates the prevailing gap in the country.

As per the International Classification of Functioning, Disability, and Health for a thorough assessment of any intervention, the measuring tool should be able to assess the impact of hemophilia on the functional capacity of the body, the patient's ability to perform daily routine exercises, and participation in social activities.[14]

Functional Independence Score in Hemophilia (FISH) is such a tool which assess performance.[15] Pettersson score is used for radiographic assessment of hemophilic joints.[16] Another established assessment tool for joint assessment is Hemophilia Joint Health Score (HJHS) score used since 2003, which was primarily designed for children with hemophilia aged 4–18 years with mild joint impairment (e.g. treated with prophylaxis) and it is along being used in adults.[17],[18] There are limited functional independence studies from India.[15],[19],[20] Moreover, only one study has attempted to evaluate the responsiveness (sensitivity to change in function due to an intervention) after physiotherapy for a specific period.[19] This study documents the responsiveness or functional improvement observed in PWH with intermittent factor VIII replacement along with physiotherapy.

  Materials and Methods Top

This quasi-experimental study was conducted in Christian Medical College, Ludhiana, over 4 months from May 1, 2016 to August 31, 2016. All PwH presenting in the outpatient department were included in this study after taking informed consent. Relevant history and clinical examination and laboratory tests were made to confirm the diagnosis wherever required.

Measurement of FVIII and inhibitor levels

FVIII levels were measured with a one-stage assay using human pooled plasma as a standard (Precision BioLogicals, Dartmouth, NS, Canada). This standard was referenced to the current World Health Organization standard for FVIII (NIBSC code 02/150). FVIII inhibitor studies were performed using the Bethesda assay.[21]

All PwH with chronic synovitis who required physiotherapy were included in the study except those patients with a prior history of hypersensitivity or anaphylaxis associated with receipt of factor VIII or IX and patients with prior inhibitor positivity. Those patients who had acute bleed (<72 h), patients with inhibitors, infection in the joint, pseudotumor with the erosion of the adjacent bone, bleeding after giving physiotherapy, and immuno-compromised patients were excluded from the study. Injection Eloctate (long-acting factor VIII) and injection Alprolix (long-acting factor IX) received through the humanitarian aid program from the World Federation of Hemophilia were used for the patients.[22]

Prophylaxis schedule for hemophilia A was 30 units per kg once a week and factor IX was 20 units per kg once a week for hemophilia B. Severity of hemophilia and response to treatment were evaluated as per the standard criteria.[23] If the patient developed breakthrough bleeding, the frequency of infusion was escalated to twice weekly after an infusion of 30%–40% factor support. The duration of therapy was as per the discretion of the physiotherapist based on his assessment and weekly improvement.

Physiotherapy plan included joint mobility exercises, upper and lower limb muscles strengthening exercises, passive manual mobilization (Grade 1) of affected joint, mild flexibility exercises, and cryotherapy. Reassessment was done every 10 days, and once the maximum improvement was noted, HJHS and FISH scores were recorded by the doctor, physiotherapist, nurse coordinator, or occupational therapist. The FISH scoring was done by eight functional activities grouped under self-care (eating and grooming, bathing, and dressing), transfer (chair and squatting), and locomotion (walking, step climbing, and running).[24] The HJHS was assessed by joint impairment and gait by rating eight items (swelling, duration of swelling, muscle atrophy, crepitus on motion, flexion loss, extension loss, joint pain, and strength) for each of the left and right elbows, knees, and ankles and a total score for each of three domains (elbow, knee, and ankle) with the addition of global gait score were calculated.

Patients documented bleeding in their in treatment diaries, and the participating families were contacted through telephone by the nurse coordinator every month to reinforce the protocol and encourage adherence. Institutional Research Committee approval was obtained.

Statistical analysis

The data were entered in a Microsoft Excel sheet. Responsiveness to treatment was assessed using the standardized response mean (SRM). Wilcoxon signed-rank test was performed due to nonparametric data distribution of the paired samples to evaluate the significance of the change in the HJHS and FISH scores obtained before and after physiotherapy in the same group of patients. All analyses were done using Statistical Package for the Social Sciences (SPSS V.21) (IBM Corp, Armonk, NY) and MedCalc (Ostend, Belgium). In a two-tailed probability distribution, the level of significance was defined as P < 0.05.

  Results Top

Forty-eight PwH were screened, and 18 PwH (16 hemophilia A and 2 hemophilia B) consented and completed the treatment protocol. Among these 18 patients, 15 were given intermittent prophylactic factors, and 3 of them received factors for breakthrough bleeds only. [Table 1] describes the severity of hemophilia, site of bleeding, and prior deformity. Patients received physiotherapy for an average of 11 days, with an average total factor consumption of 120 U/kg [Table 2]. The SRMs of pre and postphysiotherapy HJHS and FISH scores showed a statistically significant difference between the groups [Table 3].
Table 1: Baseline characteristics

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Table 2: Duration, factor consumption, and breakthrough bleeds

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Table 3: Pre and postintervention scores

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  Discussion Top

This study showed a significant difference in the FISH and HJHS scores before and after physiotherapy with intermittent factor support underscoring their utility in measuring the responsiveness to therapy. Although FISH is a valid and reliable instrument for measuring activities of self-care, transfer, and locomotion, limited studies have evaluated its responsiveness to interventions such as physiotherapy and intermittent factor support.[25] Although the current HJHS 2.1 version measures global gait score, there is only limited evidence about its utility in assessing responsiveness.[26]

The principal aim of treatment in hemophilia is to reduce the recurrence of bleeding and enhance the musculoskeletal capacity of the joints. With the use of factors as prophylaxis for PwH, life expectancy, and the quality of life have significantly improved.[27] In developing countries like India, factors replacement of <200 IU/kg/year approximates to about 10,000 units per patient per year as compared to 112,802 IU (>10 times) in high-economic ranking countries.[12]

The different consequences of the disease make the outcome assessment complicated. Outcome assessment includes annualized bleeding rate and annual joint bleed rates, HJHS, Gilbert score and active range of motion concerning musculoskeletal outcome. X rays, ultrasonography and magnetic resonance imaging we used for radiological assessment. FISH and three dimensional gait analysis for objective assessment of activities, and hemophilia activities list (HAL) and pedHAL for self reported assessment of activity.[28] The present study utilized HJHS and FISH to assess the responsiveness to intermittent prophylaxis and active physiotherapy.

Prophylactic factor therapy has shown to reduce the frequency of hemarthrosis in hemophilia and hence reduce hemophilic joint replacements.[7],[9] The rest, ice, compression, and elevation method is generally used for the management of acute joint injuries in hemophilic patients for immediate relief.[29] However, physiotherapy has shown improvement in acute joint injuries and hemarthrosis in such patients.[30],[31]

In the present study, the median age of patients observed was 25 years, and they underwent average physiotherapy for 11 days along with factor VIII therapy. The most affected joint was the knee joint followed by the elbow joint, and the least affected joint was the ankle. Other studies have also reported knee joint as the most commonly involved joints.[29],[32],[33]

In our study, the mean prescores obtained by HJHS system and FISH improved clinically and were statistically significant. Improvement was reflected by the reduction of the score in HJHS and vice versa for FISH [Table 3].

The mean quantity of factors used was 120 units per kg. Even though the cohort had three breakthrough bleeds in total, in the absence of a steady supply of prophylaxis of factors, even intermittent replacement therapy has a role in improving the joint function if combined with physiotherapy. Improvement even with the intermittent replacement therapy would also support the current policy of the government to provide as much factor as possible in the light of insufficient factors for replacement therapy. This study has shown to continue with active physiotherapy with minimal factor support for patients with joint stiffness.

[TAG:2]Conclusion [/TAG:2]

Our study highlights the utility of HJHS and FISH in assessing responsiveness to intermittent prophylaxis and physiotherapy. However, it would be imperative to follow-up these patients and assess the HJHS and FISH if the objective improvements are long lasting. Limitations of the study are small sample size and short-term follow-up. Prospective, multicentric long-term studies with stratified sampling with larger samples size may be able to overcome some of these limitations.


RS and MJJ conceptualized the study and made the design. RS, MJJ, MD, RP, GDV, and SM DV were involved in data acquisition. RS, MD, and MJJ were involved in data analysis. SM, MD, and GDV were involved in patient management over the years. RS, MJJ, and MD were involved in drafting the manuscript and proofreading. RS, MD, RP, GDV, SM, and MJJ approved the final draft of the manuscript. MJJ would be the “guarantor” about the integrity of the work.

Ethics approval


Availability of data and material



We acknowledge, Dr. Clarence J Samuel assisted in modifying the datasheet and cleaning the data, Dr. Naveen Kakkar, who proofread this and give his valuable inputs. We are also grateful for the support of the comprehensive hemophilia care team, including orthopedic department, physiotherapy, occupational therapy, physical medicine and rehabilitation team, and laboratory personnel for their support in managing the patients.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2], [Table 3]


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