Abstract
Objectives
Patients with haemophilia (PwH) often suffer from joint pain due to repetitive haemarthroses and resulting arthropathy. Literature focuses so far on pain causes, diagnosis or treatment. A summary of prevalence rates, providing facts on the absolute occurrence of pain, is not sufficiently described so far. This review aimed to explore and systematically review different pain conditions, focussing on prevalence rates of pain in adult PwH.
Methods
A review of English articles using PubMed and Web of Science was conducted in February 2020. The search strategy included patients with haemophilia A or B suffering from pain. The articles were selected based on defined PICOS-selection criteria.
Results
Out of 606 identified articles, 13 studies matched the given eligibility criteria and indicated pain prevalence rates. The weighted mean (WM) for the prevalence rate (varying timeframes) for chronic pain was 40% whereas for point prevalence the rate was WM=75%. Regarding pain intensity, findings of the EQ-5D-3L revealed moderate pain to be more present (61.0%) compared to extreme (11.6%). The main problem was the inconsistency of the definition of both acute and chronic pain as well as for prevalence types.
Conclusions
Pain is a major problem in patients with haemophilia. Pain therapy should be carried out taking into account the difference between bleeding-related or arthropathy-related causes of pain. In addition, the intensity and duration of pain should be recorded consistently to better monitor therapy and allow comparison with existing data.
Acknowledgements
The authors would like to thank Sietske De Keyser for her help in the literature search.
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Research funding: Authors state no funding involved.
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Author contributions: Pia Ransmann and Steffen Krüger and Nathalie Roussel performed the research and analysed the data. Pia Ransmann wrote the paper with support of Steffen Krüger, Thorsten Hagedorn, Thomas Hilberg and Nathalie Roussel.
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Competing interest: S. Krüger has received honoraria and travel support from Shire/Takeda and Swedish Orphan Biovitrum. S. Krüger was an employee at the Department of Sports Medicine during his work on the review and when the manuscript was written but is now employed by Takeda.
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Informed consent: This is not applicable as this article reviews prior literature.
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Ethical approval: This is not applicable as this article reviews prior literature.
References
1. Jansen, NWD, Roosendaal, G, Lafeber, FPJG. Understanding haemophilic arthropathy: an exploration of current open issues. Br J Haematol 2008;143:632–40. https://doi.org/10.1111/j.1365-2141.2008.07386.x.Search in Google Scholar PubMed
2. 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(6 Suppl):1–158. https://doi.org/10.1111/hae.14046.Search in Google Scholar PubMed
3. Krüger, S, Hoffmeister, M, Hilberg, T. Pain and structural alterations in knee joints in patients with haemophilia. Haemophilia 2018;24:657–66.10.1111/hae.13472Search in Google Scholar PubMed
4. Castaman, G, Linari, S. Prophylactic vs. on-demand treatments for hemophilia: advantages and drawbacks. Expert Rev Hematol 2018;11:567–76. https://doi.org/10.1080/17474086.2018.1486704.Search in Google Scholar PubMed
5. Oldenburg, J. Optimal treatment strategies for hemophilia: achievements and limitations of current prophylactic regimens. Blood 2015;125:2038–44. https://doi.org/10.1182/blood-2015-01-528414.Search in Google Scholar PubMed
6. Hilberg, T, Czepa, D, Freialdenhoven, D, Boettger, MK. Joint pain in people with hemophilia depends on joint status. Pain 2011;152:2029–35. https://doi.org/10.1016/j.pain.2011.04.030.Search in Google Scholar PubMed
7. Paredes, AC, Costa, P, Almeida, A, Pinto, PR. A new measure to assess pain in people with haemophilia: the multidimensional haemophilia pain questionnaire (MHPQ). PLoS One 2018;13:1–22. https://doi.org/10.1371/journal.pone.0207939.Search in Google Scholar PubMed PubMed Central
8. Krüger, S, Hilberg, T. Neuropathic pain in patients with haemophilia, that is the question. Hamostaseologie 2015;35:S5–9.10.1055/s-0037-1619823Search in Google Scholar
9. Boettger, MK, Krucker, S, Gajda, M, Schaible, HG, Hilberg, T. Repeated autologous intraarticular blood injections as an animal model for joint pain in haemophilic arthropathy. Arthritis Res Ther 2013;15:R148. https://doi.org/10.1186/ar4331.Search in Google Scholar PubMed PubMed Central
10. den Uijl, IEM, Fischer, K, Van Der Bom, JG, Grobbee, DE, Rosendaal, FR, Plug, I. Clinical outcome of moderate haemophilia compared with severe and mild haemophilia. Haemophilia 2009;15:83–90. https://doi.org/10.1111/j.1365-2516.2008.01837.x.Search in Google Scholar PubMed
11. Kalnins, W, Schelle, G, Jost, K, Eberl, W, Tiede, A. Pain therapy in haemophilia in Germany. Hamostaseologie 2015;35:167–73. https://doi.org/10.5482/HAMO-14-03-0021.Search in Google Scholar PubMed
12. Roussel, NA. Gaining insight into the complexity of pain in patients with haemophilia: state-of-the-art review on pain processing. Haemophilia 2018;24:3–8. https://doi.org/10.1111/hae.13509.Search in Google Scholar PubMed
13. van Vulpen, LFD, Holstein, K, Martinoli, C. Joint disease in haemophilia: pathophysiology, pain and imaging. Haemophilia 2018;24:44–9. https://doi.org/10.1111/hae.13449.Search in Google Scholar PubMed
14. European Patients’ Academy. Epidemiologic concepts: incidence and prevalence. Prevalence 2015;100:1–3.Search in Google Scholar
15. Witkop, M, Neff, A, Buckner, TW, Wang, M, Batt, K, Kessler, CM, et al.. Self-reported prevalence, description and management of pain in adults with haemophilia: methods, demographics and results from the pain, functional impairment, and quality of life (P-FiQ) study. Haemophilia 2017;23:556–65. https://doi.org/10.1111/hae.13214.Search in Google Scholar PubMed
16. Bondesson, E, Olofsson, T, Caverius, U, Schelin, ME, Jöud, A. Consultation prevalence among children, adolescents and young adults with pain conditions: a description of age- and gender differences. Eur J Pain 2019;24:1–21. https://doi.org/10.1002/ejp.1518.Search in Google Scholar PubMed
17. Page, MJ, Moher, D, Bossuyt, PM, Boutron, I, Hoffmann, TC, Mulrow, CD, et al.. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ 2021;372:n160. https://doi.org/10.1136/bmj.n160.Search in Google Scholar PubMed PubMed Central
18. Methley, AM, Campbell, S, Chew-Graham, C, McNally, R, Cheraghi-Sohi, S. PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv Res 2014;14:579. https://doi.org/10.1186/s12913-014-0579-0.Search in Google Scholar PubMed PubMed Central
19. Harbour, R, Miller, J. A new system for grading recommendations in evidence based guidelines. BMJ 2001;323:334–6. https://doi.org/10.1136/bmj.323.7308.334.Search in Google Scholar PubMed PubMed Central
20. Boonstra, AM, Schiphorst, HR, Reneman, MF, Posthumus, JB, Stewart, RE. Reliability and validity of the visual analogue scale for disability in patients with chronic musculoskeletal pain. Int J Rehabil Res 2008;31:165–9. https://doi.org/10.1097/mrr.0b013e3282fc0f93.Search in Google Scholar
21. Shaw, JW, Johnson, JA, Coons, SJ. US valuation of the EQ-5D health states: development and testing of the D1 valuation model. Med Care 2005;43:203–20. https://doi.org/10.1097/00005650-200503000-00003.Search in Google Scholar PubMed
22. Holstein, K, Klamroth, R, Richards, M, Carvalho, M, Pérez-Garrido, R, Gringeri, A. Pain management in patients with haemophilia: a European survey. Haemophilia 2012;18:743–52. https://doi.org/10.1111/j.1365-2516.2012.02808.x.Search in Google Scholar PubMed
23. Lorenzato, CS, Santos, RB, Fagundes, GZZ, Ozelo, MC. Haemophilia experiences, results and opportunities (HERO study) in Brazil: assessment of the psychosocial effects of haemophilia in patients and caregivers. Haemophilia 2019;25:640–50. https://doi.org/10.1111/hae.13774.Search in Google Scholar PubMed
24. Wallny, T, Hess, L, Seuser, A, Zander, D, Brackmann, HH, Kraft, CN. Pain status of patients with severe haemophilic arthropathy. Haemophilia 2001;7:453–8. https://doi.org/10.1046/j.1365-2516.2001.00540.x.Search in Google Scholar PubMed
25. Lechner, H, Schleiermacher, A, Berger, K, Schopohl, D, Schramm, W. Wishes and worries of haemophilia patients: a patient survey from Bavaria. Hamostaseologie 2017;37:117–26. https://doi.org/10.5482/hamo-16-09-0033.Search in Google Scholar PubMed
26. van Genderen, FR, Fischer, K, Heijnen, L, de Kleijn, P, van den Berg, HM, Helders, PJM, et al.. Pain and functional limitations in patients with severe haemophilia. Haemophilia 2006;12:147–53. https://doi.org/10.1111/j.1365-2516.2006.01203.x.Search in Google Scholar PubMed
27. Molho, P, Rolland, N, Lebrun, T, Dirat, G, Courpied, JP, Croughs, T, et al.. Epidemiological survey of the orthopaedic status of severe haemophilia A and B patients in France. Haemophilia 2000;6:23–32. https://doi.org/10.1046/j.1365-2516.2000.00358.x.Search in Google Scholar PubMed
28. Windyga, J, Lopaciuk, S, Stefanska, E, Juszynski, A, Wozniak, D, Strzelecki, O, et al.. Haemophilia in Poland. Haemophilia 2006;12:52–7. https://doi.org/10.1111/j.1365-2516.2006.01188.x.Search in Google Scholar PubMed
29. Fischer, K, Poonnoose, P, Dunn, AL, Babyn, P, Manco-Johnson, MJ, David, JA, et al.. Choosing outcome assessment tools in haemophilia care and research: a multidisciplinary perspective. Haemophilia 2017;23:11–24. https://doi.org/10.1111/hae.13088.Search in Google Scholar PubMed
30. Davari, M, Gharibnaseri, Z, Ravanbod, R, Sadeghi, A. Health status and quality of life in patients with severe hemophilia A: a cross-sectional survey. Hematol Rep 2019;11:39–42. https://doi.org/10.4081/hr.2019.7894.Search in Google Scholar PubMed PubMed Central
31. Witkop, M, Guelcher, C, Forsyth, A, Hawk, S, Curtis, R, Kelley, L, et al.. Treatment outcomes, quality of life, and impact of hemophilia on young adults (aged 18–30 years) with hemophilia. Am J Hematol 2015;90:S3–10. https://doi.org/10.1002/ajh.24220.Search in Google Scholar PubMed
32. von Mackensen, S, Harrington, C, Tuddenham, E, Littley, A, Will, A, Fareh, M, et al.. The impact of sport on health status, psychological well-being and physical performance of adults with haemophilia. Haemophilia 2016;22:521–30. https://doi.org/10.1111/hae.12912.Search in Google Scholar PubMed
33. Elander, J, Barry, T. Analgesic use and pain coping among patients with haemophilia. Haemophilia 2003;9:202–13. https://doi.org/10.1046/j.1365-2516.2003.00723.x.Search in Google Scholar PubMed
34. Kim, S-Y, Kim, S-W, Kim, J-M, Shin, I-S, Bael, H-J, Lee, H-S, et al.. Impact of personality and depression on quality of life in patients with severe haemophilia in Korea. Haemophilia 2013;19:e270–5. https://doi.org/10.1111/hae.12221.Search in Google Scholar PubMed
35. Gilbert, M. Prophylaxis: musculoskeletal evaluation. Semin Hematol 1993;30:3–6.Search in Google Scholar
36. Finnerup, NB, Scholz, J, First, MB, Barke, A, Cohen, M, Smith, BH, et al.. Chronic pain as a symptom or a disease. Pain 2018;160:19–27.10.1097/j.pain.0000000000001384Search in Google Scholar PubMed
37. Treede, R, Rief, W, Barke, A, Aziz, Q, Bennett, M, Benoliel, R, et al.. Chronic pain as a symptom or a disease: the IASP classification of chronic pain for the international classification of diseases (ICD-11). Pain 2019;160:19–27. https://doi.org/10.1097/j.pain.0000000000001384.Search in Google Scholar
38. Timmer, MA, Pisters, MF, de Kleijn, P, de Bie, RA, Fischer, K, Schutgens, RE. Differentiating between signs of intra-articular joint bleeding and chronic arthropathy in haemophilia: a narrative review of the literature. Haemophilia 2015;21:289–96. https://doi.org/10.1111/hae.12667.Search in Google Scholar PubMed
39. Hoots, WK, Ebbesen, LS, Konkle, BA, Auerswald, GKH, Roberts, HR, Weatherall, J, et al.. Secondary prophylaxis with recombinant activated factor VII improves health-related quality of life of haemophilia patients with inhibitors. Haemophilia 2008;14:466–75. https://doi.org/10.1111/j.1365-2516.2008.01654.x.Search in Google Scholar PubMed
40. Krüger, S, Hilberg, T, Cook, DA, Reed, DA, Krüger, S, Hoffmeister, M, et al.. Prophylactic vs. on-demand treatments for hemophilia: advantages and drawbacks. Haemophilia 2018;11:567–76.Search in Google Scholar
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