MASAC Document 283 - Physical Therapy Management for People with Bleeding Disorders and Chronic Pain

Authors:

Nancy Durben, PT, MSPT, PCS (1), J. Nicole Clark, PT, DPT (2), Jennifer R Newman, PT, MSPT (3), Lora Joyner, PT, MS (4), Ryan J. Rushton, PT, DPT, MHA, CLT (5), Lena M. Volland, PT, PhD(c) (6), Tyler Buckner, MD (2)

Affiliations:

(1) The Hemostasis and Thrombosis Center at Oregon Health and Science University

(2) University of Colorado Hemophilia and Thrombosis Center

(3) University of North Carolina at Chapel Hill Hemophilia and Thrombosis Center

(4) East Carolina University Hemophilia Treatment Center

(5) Utah Valley University, Department of Allied Health

(6) The National Bleeding Disorders Foundation

Executive Summary

The Pain Initiative Taskforce (PITF) of the National Bleeding Disorder Foundation’s (NBDF) Medical and Scientific Advisory Council (MASAC) convened an expert panel of physical therapists to develop recommendations for the physical therapy specific assessment and treatment of chronic pain in people with bleeding disorders (PWBD). The recommendations are based on a systematic review of the published medical literature, professional experiences of the panel experts, and external multistakeholder reviews.

Recommendations

1. Assessment
2. Physical therapists evaluating people with a bleeding disorder and chronic pain should utilize a combination of patient and clinician reported measures of health-related quality of life (HRQOL) and functional outcomes to best identify a plan of care focusing on patient-specific impairments and goals. 

1. Treatment: All PWBD experiencing chronic pain should:
2. receive education on pain.
3. receive education on musculoskeletal anatomy, biomechanics, and joint health.
4. receive education on the safety and efficacy of exercise.
5. receive education on prevention and treatment of bleeding episodes.
6. be offered aquatic intervention as part of their physical therapy plan of care.
7. receive an individualized therapeutic exercise program.
8. participate in a pain management program with psychosocial support to reduce pain’s impact and support skilled therapeutic exercise programs. 
9. be offered therapeutic modalities as part of a multimodal treatment approach for chronic pain.
10. be offered manual therapy interventions as part of an individualized treatment program.

INTRODUCTION

Background

Chronic pain is one of the most common chronic conditions in the United States (US),¹ with annualized prevalence among of 20.4%. The diagnosis of chronic pain is widely used to describe an innumerable number of clinical presentations. It is multifactorial, associated with actual and or potential tissue damage, and is defined as pain that lasts longer than three months extending past normal healing time.² Research in people with hemophilia (PWH) shows a high prevalence of chronic pain with 34-58% living with chronic pain,³ 39% describing poorly managed pain,⁴ and pain that affects general activity (74%), walking ability (70%), normal work (71%) and relations with other people 56%.⁵ While the prevalence of chronic pain in PWH is documented in the literature, improving the clinical treatment of chronic pain represents a critical need and priority for PWBD.

The impact of chronic pain on function and quality of life (QOL) is individual, specific, multifaceted, and dynamic. In PWBD, recurrent bleeding episodes cause progressive musculoskeletal (MSK) changes that impact bone, cartilage, and muscle. The pain experience in PWBD depends on many factors including MSK tissue damage, previously available treatment methods, medical experience and trauma, and one’s personal family history involving bleeding disorders⁶. Pain intensity and pain interference varies among PWBD even those with similar clinical presentations.^{7, 8}The biopsychosocial model of healthcare allows consideration of many factors which contribute to the experience of chronic pain. This model can identify and explain differences between individuals and establish a foundation for the interdisciplinary, multimodal management of pain. 

Rationale 

This document provides practical guidance to physical therapists who care for PWBD experiencing chronic pain. It serves as a companion to the document “Management of Chronic Pain in Persons with Bleeding Disorders: Guidance for Practical Application of The Centers for Disease Control’s Opioid Prescribing Guidelines”,⁹ which was published by MASAC in 2020. This also is a companion document to the document “MASAC Recommendations Regarding Physical Therapy Management for the Care of Persons with Bleeding Disorders”.¹⁰ 

Scope and Audience

The recommendations provided in this document are intended for physical therapists working with PWBD experiencing chronic pain. Chronic pain in PWBD is often due to the sequelae of joint bleeding and damage; however, the described practices can be applied to PWBD experiencing chronic musculoskeletal pain regardless of location.   

Methods and Process

The interdisciplinary PITF was formed by the NBDF MASAC leadership to address the issue of chronic pain in the inherited bleeding disorders community. The PITF is an expert panel of clinicians and community members working in the bleeding disorder community and includes clinicians in medicine, social work, psychology, physical therapy, nursing, and community members. The physical therapy subcommittee of this taskforce led the development of the physical therapy-specific recommendations for the assessment and treatment of chronic pain in PWBD. 

The subcommittee conducted a systematic review of available evidence through July 2022 to guide the development of the recommendations presented in this document. PubMed was used to identify current literature regarding chronic pain assessment and management in PWBD. Only full-text articles were included, with no restriction on date of publication, age of participants, or original language of article. There were forty-three articles reviewed and after thorough screening of abstracts, twenty-five articles were identified as addressing PWBD, chronic pain, and physical therapy interventions. They were then evaluated using components of the GRADE process. Thirteen additional articles were identified through the review process and included.

The strength and quality of evidence in the literature and expert opinion of assessment and treatment of chronic pain were considered in these recommendations. Draft recommendations were reviewed and revised by all members of the MASAC PITF and made available for external review by the NBDF’s Physical Therapy Working Group. Pertinent comments were integrated and addressed in the final version of this document. 

The final recommendations were organized into 2 domains based on the research studies identified in the literature: (1) Assessment and (2) Treatment. Treatment was further subdivided into 5 categories: (1) Education, (2) Aquatic Therapy, (3) Therapeutic Exercise, (4) Therapeutic Modalities, and (5) Manual Therapy.   

RECOMMENDATIONS 

Physical therapy stands as a pivotal cornerstone in chronic pain management. Navigating chronic pain demands a comprehensive perspective, delving into the biopsychosocial intricacies of the pain experience.⁹ The imperative lies in tailoring the treatment strategies to the distinct requirements of every individual. Skilled physical therapists can utilize the recommendations below to curate a chronic pain care plan for PWBD. 

A physical therapist’s close collaboration with the hematology provider is necessary to ensure appropriate medical management, factor levels, and referrals to other care providers.  Common medications prescribed to maintain hemostasis prophylactically or on demand include but not limited to factor replacement, bispecific antibodies, antifibrinolytics, and desmopressin.  Medication management for chronic pain may require ongoing monitoring by prescribing medical providers. Analgesic medication use prior to or after exercising, if required, should be directed by the medical provider, and requires continual re-evaluation so that medications can be titrated to effect or stopped when no longer necessary.⁹ 

Patient involvement and adherence to the plan of care is paramount and increases the likelihood of optimal outcomes.

1. ASSESSMENT

Rationale: A well-rounded, holistic assessment is essential to evaluate health status, guide treatment, and assess the effects of treatment in PWBD who experience chronic pain. There are several outcome measures identified as valid and reliable for use in PWBD.^{5, 11, 12} However, a combination of assessment tools can best address the complex nature of pain as understood within the framework of the biopsychosocial model.⁷ By utilizing disease-specific functional assessment tools in combination with pain and HRQOL measures, physical therapists can promote patient engagement, target functional impairments, establish a plan of care, and assess outcomes of pain management interventions for PWBD. Chronic pain requires a interdisciplinary, multimodal approach with pain assessments across multiple domains (Table 1). Use of a Numeric Rating Scale (NRS) or Visual Analog Scale (VAS) alone for assessing chronic pain is inadequate.

1. Physical therapists evaluating people with a bleeding disorder and chronic pain should utilize a combination of patient and clinician reported measures of HRQOL and functional outcomes to best identify a plan of care focusing on patient-specific impairments and goals.  (Table 1) 

Practice implications: Bleeding disorder-specific assessment tools evaluate joint and muscle health, self-reports of pain and function, and HRQOL. An individual’s specific impairment and participation goals will guide the choice of assessment tools and outcome measures. Multiple tools are required to fully evaluate pain, target interventions, guide the physical therapy plan of care and track outcomes. Pain assessment should not be limited to NRS and VAS scales alone.¹² [Table 1] Clinicians are encouraged to choose a core set of outcomes measures to follow in all patients with pain and use additional measures as guided by each patient’s clinical needs and goals.

Special considerations: Given the biopsychosocial nature of pain, it is recommended a psychosocial clinician (i.e., a specialist in behavioral and mental health assessment and intervention) be incorporated into an individualized pain management program.^{13, 14} 

1. TREATMENT

Education

Rationale: Patient education is an individualized, collaborative process between health care providers and patients to foster the integration of knowledge, skills, and attitudes to achieve optimal health outcomes.¹⁵ Education, including the neurophysiology and neurobiology of pain, can positively affect perceived pain intensity, level of catastrophizing, kinesiophobia, and impact of pain on daily functioning.^{15, 16} Additional education on musculoskeletal anatomy, biomechanics, joint health, safety and efficacy of exercise, and prevention and treatment of bleeding episodes support PWBD to reach their goals.¹⁷ 

1. All PWBD experiencing chronic pain should receive pain education. 

Practice implication: Pain education should be integrated into routine clinical practice for managing pain in PWBD to align beliefs and knowledge with current evidence-based pain science. The utilization of pain science assessment tools (e.g. COPI, rNPQ) is highly encouraged to identify the knowledge gaps and misconceptions, target education, and evaluate the effectiveness of pain education.^{16, 18-20} 

Special consideration: It is essential to acknowledge the tissue damage, tissue alterations, and resultant biomechanical changes in PWBD with hemophilic arthropathy.⁶ 

1. All PWBD experiencing chronic pain should receive education on musculoskeletal anatomy, biomechanics, and joint health. 

Practice implication: Education on musculoskeletal anatomy, biomechanics, and joint health should be integrated into routine clinical practice for managing pain in PWBD to enhance understanding of body functions and impairments. It is essential to consider the clinical presentation in addition to the diagnosis to tailor the education to the patient’s needs.^{18, 19} 

1. All PWBD experiencing chronic pain should receive education on the safety and efficacy of exercise. 

Practice implication: Education on the safety and efficacy of exercise should be integrated into routine clinical practice for managing pain in PWBD to encourage regular physical activity and decrease kinesiophobia. Treatment interventions (i.e., guided, skilled therapeutic exercises, aquatic therapy, and aerobic conditioning) have been shown to be safe and effective in the management of chronic pain in PWBD.^{18, 20, 21}

1. All PWBD experiencing chronic pain should receive education on prevention and treatment of bleeding episodes. 

Practice implication: Education on prevention and treatment of bleeding episodes should be integrated into routine physical therapy clinical care for managing pain in PWBD to enhance patient independence and competence. Competent self-management in the prevention and treatment of bleeding episodes will enable and broaden options of activity participation for PWBD experiencing chronic pain.^{6, 18} 

Aquatic Exercise  

Rationale: Aquatic Exercise has many different names (hydrotherapy, aquatherapy, hydro kinesiotherapy, aquatic therapy, training in pool). It is performed in warm water and is one of the oldest therapeutic interventions. The properties of water, including hydrostatic pressure, buoyancy, and temperature (33-34 Deg C) impact an individual’s physiology by improving circulation, increasing parasympathetic response, and decreasing weight bearing.  Skillful utilization of these properties during aquatic exercise reduces pain, improves functional capacity, allows for movement in all planes, and improves strength.²²   

1. All PWBD experiencing chronic pain should be offered aquatic intervention as part of their physical therapy plan of care. 

Practice Implication: Aquatic exercise can improve joint range of motion, strength, aerobic function, and pain intensity in PWBD. Buoyancy decreases compressive and gravitational forces on joints during immersion which promotes active participation in therapy. Aquatic exercise is shown to be an effective intervention for pain relief.^{21, 23, 24}

Special consideration: Access to an aquatic environment may be limited by several external factors (i.e., insurance, culture, location, entrance/exit to pool). Additionally, medical clearance is required for individuals who have immune deficiency, central venous catheters, skin conditions, cardiovascular disease, chronic kidney disease, pregnancy, and thermoregulation difficulties.  

Therapeutic Exercise

Rationale: PWBD who experience soft tissue, joint, and muscle bleeds may present with decreased range of motion and impaired muscle activation that can negatively impact participation, activities of daily living, and hobbies.²⁵ Therapeutic exercise is a broad category of physical therapy interventions used to address impairments and maximize function and participation. 

1. All PWBD experiencing chronic pain should receive an individualized therapeutic exercise program.

Practice Implications: A combination of therapeutic exercise types (i.e., strengthening, stretching, aerobic exercise, and functional activities) is used to individualize a program to meet the needs of the patient.^{18, 20, 23, 24, 26-29} Therapeutic exercise programs with variable duration, frequency, and intensity have shown to be safe in PWBD and effective in decreasing the experience of chronic pain.

Special Consideration: The research available reinforces the importance of bleed prevention strategies when engaging in therapeutic exercise. Prior to initiation of plan of care, use of medications to prevent bleeding before or after exercise should be discussed with the treating hematologist.^{27, 29}

1.  All PWBD experiencing chronic pain should participate in a pain management program with psychosocial support to reduce pain’s impact and support skilled therapeutic exercise programs. 

Practice Implication: Skilled therapeutic exercise and cognitive-behavioral therapy support the biopsychosocial treatment model for chronic pain.  Used in combination, improvements in self-efficacy, QOL and emotional status, while reducing pain and kinesiophobia are shown when compared to therapeutic exercise alone.¹⁹ 

Special Consideration: Mental health service access and an individual’s receptiveness to intervention may vary. 

Therapeutic Modalities 

Rationale: Therapeutic modalities are part of a larger biophysical agent category, including electromagnetic, thermal, and mechanical tools, utilized by physical therapists to relieve pain and reduce inflammation. These are often combined with other skilled PT interventions in a comprehensive pain management plan of care.²⁸ 

1. PWBD experiencing chronic pain should be offered therapeutic modalities as part of a multimodal treatment approach for chronic pain. 
   1. Electrotherapy modalities (Transcutaneous Electrical Nerve Stimulation (TENS), electromagnetic field, high intensity laser therapy) are insufficiently studied in PWBD with chronic pain; however, they can be considered as part of an individualized plan of care.^{24, 30} 

Practice Implications:

1. Cryotherapy and heat therapy: Although the use of cryotherapy has been studied in this population for treatment during acute bleeding events, the use of cryotherapy has not been fully examined for chronic pain. The use of heat as a modality exists in many forms, for example therapeutic ultrasound, hot packs, and diathermy. As with many existing therapeutic modalities, research investigating the efficacy and safety of these modalities in PWBD with chronic pain is extremely limited.^{24, 30}

Special Consideration: Due to lack of high-level evidence, using therapeutic modalities with PWBD should be considered carefully and monitored over time. Other modalities, such as dry needling, acupressure, cupping, blood flow restriction, and instrument assisted soft tissue mobilization have not been studied in the PWBD population and chronic pain, and therefore should be used with caution and in coordination with the hematology health care provider due to their mechanism of action and potentially increased risk for bleeding. 

Manual Therapy 

Rationale: Manual therapy involves the mobilization of soft tissues through joint traction, muscle stretching, joint mobilization, and proprioceptive neuromuscular facilitation to improve mobility, functionality, and reduce pain. PWBD may present with altered limb alignment, contractures, loss of soft tissue and bony structure integrity, weakness, altered proprioception and kinesiophobia that result in chronic pain and impact HRQOL, functional mobility, and ADLs. Manual therapy is utilized to address the soft tissue restrictions that result from recurrent bleeding events.

1. PWBD experiencing chronic pain should be offered manual therapy interventions as part of an individualized treatment program.

Practice implications: Manual therapy (grades 1 and 2 joint mobilizations) has been studied in PWBD. These investigations suggest that manual therapy is safe and did not cause bleeding events.^{20, 31-35} It was shown to be effective in improving range of motion by mobilizing soft tissues, such as the joint capsule, muscle, and fascia.^{20, 31-35} Further benefits in pain perception,^{20, 31, 32, 34, 35} functional mobility,³⁴ proprioception,²⁰ muscle strength,^{20, 35} QOL,²⁰ and perception of disease²⁰ can occur.^{20, 34, 35}

Special Considerations: Due to potential risk of injury and bleeding complications, grade 4 mobilizations and grade 5 manipulations are not recommended. 

Recommended Physical Therapy Assessment Tools for the Evaluation of Chronic Pain (Table 1) 

* Indicates recommended tool. Table 1 provides evidenced based assessment tools available for the clinician to utilize based on their clinical judgement. The recommended assessment tools represent a quick reference guide for each area of impairment.

Glossary of Terms

Conclusion

More research is needed to specifically address pediatric chronic pain, the addition of complementary and alternative medicine in combination with physical therapy treatments, and the impact of chronic pain on all PWBD.  These recommendations do not represent the extensive skill set that physical therapists bring to the treatment of chronic pain but summarize the research that is currently published. Using available research and expert opinion, these recommendations will improve the function, QOL, and pain intensity of PWBD.

Acknowledgement

The authors would like to acknowledge all the members of the National Bleeding Disorders Foundation’s MASAC Pain Initiative Subcommittee and the National Bleeding Disorder Foundation’s Physical Therapy Working Group for their assistance in editing and providing feedback for these recommendations.  

References

1.         Dahlhamer J, Lucas J, Zelaya C, Nahin R, Mackey S, DeBar L, et al. Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults - United States, 2016. MMWR Morb Mortal Wkly Rep. 2018;67(36):1001-6.

2.         WHO. ICD-11 for Mortality and Morbidity Statistics 2023 [Available from: https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/1581976053.

3.         Paredes AC, Teixeira P, Almeida A, Pinto PR. Prevalence and Interference of Chronic Pain Among People With Hemophilia: A Systematic Review and Meta-Analysis. J Pain. 2021;22(10):1134-45.

4.         Witkop M, Lambing A, Divine G, Kachalsky E, Rushlow D, Dinnen J. A national study of pain in the bleeding disorders community: a description of haemophilia pain. Haemophilia. 2012;18(3):e115-9.

5.         Buckner TW, Batt K, Quon D, Witkop M, Recht M, Kessler C, et al. Assessments of pain, functional impairment, anxiety, and depression in US adults with hemophilia across patient-reported outcome instruments in the Pain, Functional Impairment, and Quality of Life (P-FiQ) study. European Journal of Haematology. 2018;100:5-13.

6.         Gualtierotti R, Tafuri F, Arcudi S, Solimeno PL, Acquati J, Landi L, et al. Current and Emerging Approaches for Pain Management in Hemophilic Arthropathy. Pain and Therapy. 2022;11(1):1-15.

7.         Chantrain VA, Guillaume S, Foubert A, Meeus M, Lobet S, Lambert C, et al. Discordance between joint pain and imagery severity in the ankle joint and contributors of lower limb activity limitations in adults with haemophilia: A cross‐sectional study. Haemophilia. 2023;29(2):648-57.

8.         Roussel NA, Chantrain VA, Foubert A, Lambert C, Hermans C, Meeus M, et al. Gaining more insight into ankle pain in haemophilia: A study exploring pain, structural and functional evaluation of the ankle joint. Haemophilia. 2022;28(3):480-90.

9.         Buckner T, et al. MASAC Document 260 - Management of Chronic Pain in Persons with Bleeding Disorders: Guidance for Practical Application of The Centers for Disease Control's Opioid Prescribing Guidelines Hemophilia.org2020 [Available from: https://www.hemophilia.org/healthcare-professionals/guidelines-on-care/masac-documents/masac-document-260-management-of-chronic-pain-in-persons-with-bleeding-disorders-guidance-for-practical-application-of-the-centers-for-disease-controls-opioid-prescribing-guidelines.

10.       Joyner L, et al. MASAC Document 275 - MASAC Recommendations Regarding Physical Therapy Management for the Care of Persons with Bleeding Disorders Hemophilia.org2022 [Available from: https://www.hemophilia.org/healthcare-professionals/guidelines-on-care/masac-documents/masac-document-275-masac-recommendations-regarding-physical-therapy-management-for-the-care-of-persons-with-bleeding-disorders.

11.       Kuijlaars IAR, Emst M, Net J, Timmer MA, Fischer K. Assessing the test–retest reliability and smallest detectable change of the Haemophilia Activities List. Haemophilia. 2021;27(1):108-12.

12.       Batt K, Recht M, Cooper DL, Iyer NN, Kempton CL. Construct validity of patient-reported outcome instruments in US adults with hemophilia: results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study. Patient Prefer Adherence. 2017;11:1369-80.

13.       Stromer W, Pabinger I, Ay C, Crevenna R, Donnerer J, Feistritzer C, et al. Pain management in hemophilia: expert recommendations. Wiener klinische Wochenschrift. 2021;133(19-20):1042-56.

14.       Cassis FRMY, Querol F, Forsyth A, Iorio A. Psychosocial aspects of haemophilia: a systematic review of methodologies and findings. Haemophilia. 2012;18(3):e101-e14.

15.       Bastable SB. Essentials of Patient Education: Jones & Bartlett Learning; 2017.

16.       Louw A, Zimney K, Puentedura EJ, Diener I. The efficacy of pain neuroscience education on musculoskeletal pain: A systematic review of the literature. Physiotherapy Theory and Practice. 2016;32(5):332-55.

17.       Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, et al. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020;26(S6):1-158.

18.       Cuesta-Barriuso R, Torres-Ortuño A, Nieto-Munuera J, López-Pina JA. Effectiveness of an Educational Physiotherapy and Therapeutic Exercise Program in Adult Patients With Hemophilia: A Randomized Controlled Trial. Arch Phys Med Rehabil. 2017;98(5):841-8.

19.       García-Dasí M, Pérez-Alenda S, Carrasco JJ, Marques-Sule E, Aguilar-Rodríguez M, Moreno-Segura N, et al. Effects of a non-pharmacological approach for chronic pain management in patients with haemophilia: efficacy of cognitive-behavioural therapy associated with physiotherapy. Haemophilia. 2021;27(3):e357-e67.

20.       Cuesta-Barriuso R. Effectiveness of Physiotherapy in the Treatment of Hemophilic Arthropathy a Systematic Review. Annals of Hematology & Oncology. 2017;4(9).

21.       Neelapala YVR, Attal R, Tandale S. Aquatic exercise for persons with haemophilia: A review of literature. Complement Ther Clin Pract. 2019;34:195-200.

22.       Mazloum V, Rahnama N, Khayambashi K. Effects of therapeutic exercise and hydrotherapy on pain severity and knee range of motion in patients with hemophilia: a randomized controlled trial. Int J Prev Med. 2014;5(1):83-8.

23.       Siqueira TC, Dominski FH, Andrade A. Effects of exercise in people with haemophilia: An umbrella review of systematic reviews and meta‐analyses. Haemophilia. 2019;25(6):928-37.

24.       McLaughlin P, Hurley M, Chowdary P, Khair K, Stephensen D. Physiotherapy interventions for pain management in haemophilia: A systematic review. Haemophilia. 2020;26(4):667-84.

25.       Guodemar-Pérez J, Ruiz-López M, Rodríguez-López E, García-Fernández P, Hervás-Pérez JP. Physiotherapy Treatments in Musculoskeletal Pathologies Associated with Haemophilia. Hamostaseologie. 2018;38(3):141-9.

26.       Hill K, Fearn M, Williams S, Mudge L, Walsh C, McCarthy P, et al. Effectiveness of a balance training home exercise programme for adults with haemophilia: a pilot study. Haemophilia. 2010;16(1):162-9.

27.       Scaturro D, Benedetti MG, Lomonaco G, Tomasello S, Farella MGG, Passantino G, et al. Effectiveness of rehabilitation on pain and function in people affected by hemophilia. Medicine (Baltimore). 2021;100(50):e27863.

28.       Salim M, Brodin E, Spaals-Abrahamsson Y, Berntorp E, Zetterberg E. The effect of Nordic Walking on joint status, quality of life, physical ability, exercise capacity and pain in adult persons with haemophilia. Blood Coagul Fibrinolysis. 2016;27(4):467-72.

29.       Calatayud J, Pérez-Alenda S, Carrasco JJ, Cruz-Montecinos C, Andersen LL, Bonanad S, et al. Safety and Effectiveness of Progressive Moderate-to-Vigorous Intensity Elastic Resistance Training on Physical Function and Pain in People With Hemophilia. Phys Ther. 2020;100(9):1632-44.

30.       Watson T. Current concepts in electrotherapy. Haemophilia. 2002;8(3):413-8.

31.       Donoso-Úbeda E, Meroño-Gallut J, López-Pina JA, Cuesta-Barriuso R. Safety and effectiveness of fascial therapy in adult patients with hemophilic arthropathy. A pilot study. Physiotherapy Theory and Practice. 2018;34(10):757-64.

32.       Cuesta-Barriuso R, Trelles-Martínez RO. Manual therapy in the treatment of patients with hemophilia B and inhibitor. BMC Musculoskeletal Disorders. 2018;19(1).

33.       Cuesta-Barriuso R, Gómez-Conesa A, López-Pina J-A. Manual therapy in the treatment of ankle hemophilic arthropathy. A randomized pilot study. Physiotherapy Theory and Practice. 2014;30(8):534-9.

34.       Donoso-Úbeda E, Meroño-Gallut J, López-Pina JA, Cuesta-Barriuso R. Safety of fascial therapy in adult patients with hemophilic arthropathy of ankle. A cohort study. Musculoskelet Sci Pract. 2018;35:90-4.

35.       Cuesta-Barriuso R, Gómez-Conesa A, López-Pina J-A. Manual and educational therapy in the treatment of hemophilic arthropathy of the elbow: a randomized pilot study. Orphanet Journal of Rare Diseases. 2018;13(1).

36.       Witkop M, Santaella M, Nichols CD, Lambing AY, Baumann K, Curtis RG, et al. Understanding the Pain Management Landscape Within the US Bleeding Disorder Community: A Multi-Center Survey. Pain Med. 2022;23(2):269-79.

37.       Hermans C, De Moerloose P, Fischer K, Holstein K, Klamroth R, Lambert T, et al. Management of acute haemarthrosis in haemophilia A without inhibitors: literature review, European survey and recommendations. Haemophilia. 2011;17(3):383-92.

38.       Santavirta N, Solovieva S, Helkama O, Lehto S, Konttinen Y, Santavirta S. Musculoskeletal pain and functional ability in haemophilia A and B. Physiotherapy and rehabilitation in haemophilia patients. Rheumatology International. 2001;21(1):15-9.

39.       Cuesta-Barriuso R, Gómez-Conesa A, López-Pina JA. Effectiveness of two modalities of physiotherapy in the treatment of haemophilic arthropathy of the ankle: a randomized pilot study. Haemophilia. 2014;20(1):e71-e8.

40.       St‐Louis J, Abad A, Funk S, Tilak M, Classey S, Zourikian N, et al. The Hemophilia Joint Health Score version 2.1 Validation in Adult Patients Study: A multicenter international study. Research and Practice in Thrombosis and Haemostasis. 2022;6(2):e12690.

41.       Strike K, Mulder K, Michael R. Exercise for haemophilia. Cochrane Database of Systematic Reviews. 2016;2016(12).

42.       Pate JW, Simons LE, Rush G, Hancock MJ, Hush JM, Verhagen A, et al. The Concept of Pain Inventory for Adults (COPI-Adult): Assessing Knowledge and Beliefs Regarding Pain Science Education. Clin J Pain. 2021;38(1):32-40.

43.       Vaughan B, Mulcahy J, Fitzgerald K, Austin P. Evaluating Patient's Understanding of Pain Neurophysiology: Rasch Analysis of the Neurophysiology of Pain Questionnaire. Clin J Pain. 2019;35(2):133-9.

44.       Van Balen EC, Haverman L, Hassan S, Taal EM, Smit C, Driessens MH, et al. Validation of PROMIS Profile‐29 in adults with hemophilia in the Netherlands. Journal of Thrombosis and Haemostasis. 2021;19(11):2687-701.

45.       Cella D, Choi SW, Condon DM, Schalet B, Hays RD, Rothrock NE, et al. PROMIS Adult Health Profiles: Efficient Short-Form Measures of Seven Health Domains. Value Health. 2019;22(5):537-44.

46.       Beaton DE, Katz JN, Fossel AH, Wright JG, Tarasuk V, Bombardier C. Measuring the whole or the parts? Validity, reliability, and responsiveness of the Disabilities of the Arm, Shoulder and Hand outcome measure in different regions of the upper extremity. J Hand Ther. 2001;14(2):128-46.

47.       Hale SA, Hertel J. Reliability and Sensitivity of the Foot and Ankle Disability Index in Subjects With Chronic Ankle Instability. J Athl Train. 2005;40(1):35-40.

48.       Zigler JE, Delamarter RB. Oswestry disability index. J Neurosurg Spine. 2014;20(2):241-2.

49.       Vernon H, Mior S. The Neck Disability Index: a study of reliability and validity. J Manipulative Physiol Ther. 1991;14(7):409-15.

50.       Nilsdotter AK, Lohmander LS, Klässbo M, Roos EM. Hip disability and osteoarthritis outcome score (HOOS)--validity and responsiveness in total hip replacement. BMC Musculoskelet Disord. 2003;4:10.

51.       Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS)--development of a self-administered outcome measure. J Orthop Sports Phys Ther. 1998;28(2):88-96.

52.       Vincent JI, MacDermid JC, King GJW, Grewal R. Rasch analysis of the Patient Rated Elbow Evaluation questionnaire. Health and Quality of Life Outcomes. 2015;13(1):84.

53.       Ferraz MB, Quaresma MR, Aquino LR, Atra E, Tugwell P, Goldsmith CH. Reliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis. J Rheumatol. 1990;17(8):1022-4.

54.       Jensen MP, McFarland CA. Increasing the reliability and validity of pain intensity measurement in chronic pain patients. Pain. 1993;55(2):195-203.

55.       Cao ZB, Miyatake N, Aoyama T, Higuchi M, Tabata I. Prediction of maximal oxygen uptake from a 3-minute walk based on gender, age, and body composition. J Phys Act Health. 2013;10(2):280-7.

56.       Kubo H, Asai T, Fukumoto Y, Oshima K, Koyama S, Monjo H, et al. Value of the 3-min walk test and its association with motor functions in older adults. Physiotherapy Theory and Practice. 2022:1-9.

57.       Binkley JM, Stratford PW, Lott SA, Riddle DL. The Lower Extremity Functional Scale (LEFS): scale development, measurement properties, and clinical application. North American Orthopaedic Rehabilitation Research Network. Phys Ther. 1999;79(4):371-83.

58.       Carroll D. A quantitative test of upper extremity function. Journal of Chronic Diseases. 1965;18(5):479-91.