Possible Targets to Reduce Fatigue in Chronic Immune Thrombocytopenia Patients – An Explorative Study

Wobke E.M. van Dijk; Merel M. Nap-van der Vlist; Hans Knoop; Roger E.G. Schutgens

doi:10.1055/s-0042-1758546

TH Open, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · TH Open 2022; 06(04): e387-e395
DOI: 10.1055/s-0042-1758546

Original Article

Possible Targets to Reduce Fatigue in Chronic Immune Thrombocytopenia Patients – An Explorative Study

Wobke E.M. van Dijk

¹Center for Benign Hematology, Thrombosis and Hemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

,

Merel M. Nap-van der Vlist

²Department of Social Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

,

Hans Knoop

³Department of Medical Psychology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Public health research institute, Amsterdam, The Netherlands

,

Roger E.G. Schutgens

¹Center for Benign Hematology, Thrombosis and Hemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

› Institutsangaben

Abstract

Background Fatigue in immune thrombocytopenia (ITP) is frequent and burdensome, but we lack the knowledge to help these patients.

Aim The aim of the study is to explore the role of disease activity and other potentially modifiable factors in fatigue.

Method This cross-sectional study included adult chronic ITP patients (n = 59). Univariable linear regression (corrected for confounders) was used to determine the relationship between disease activity (platelet count <30 × 10⁹/L or treatment), disease-specific factors (bleeding symptoms, ferritin), and transdiagnostic factors (FACT-G physical/functional/emotional/social well-being subscales, physical activity level, and vitamin D) and fatigue (Checklist Individual Strength fatigue subscale). Several multivariable models with clustered sets of variables were used to compare the proportion of explained variance of fatigue (adjusted R ²).

Results Significant relations with moderate effect sizes (>0.50) were found for physical and functional well-being and fatigue, and physical activity and fatigue. Other significant relations with fatigue (effect size 0.30–0.47) included skin and organ bleeding, emotional and social well-being, vitamin D, and disease activity. Notably, the models with disease activity and disease-specific factors explained <20% of the variance in fatigue, while the models with transdiagnostic factors (functioning and physical activity) explained >50%. Vitamin D alone explained 12% of the variance in fatigue.

Conclusion Transdiagnostic (non-disease-specific) rather than disease-specific factors explained a large part of the variance in ITP-related fatigue. Many factors related to fatigue are potentially modifiable and should be investigated as targets for interventions.

Keywords

fatigue - immune thrombocytopenia - modifiable factors - disease activity - transdiagnostic

Volltext

Referenzen

References
1 Al-Samkari H, Kuter DJ. Immune thrombocytopenia in adults: modern approaches to diagnosis and treatment. Semin Thromb Hemost 2020; 46 (03) 275-288
2 Cooper N, Kruse A, Kruse C. et al. Immune thrombocytopenia (ITP) World Impact Survey (iWISh): patient and physician perceptions of diagnosis, signs and symptoms, and treatment. Am J Hematol 2021; 96 (02) 188-198
3 Efficace F, Mandelli F, Fazi P. et al. Health-related quality of life and burden of fatigue in patients with primary immune thrombocytopenia by phase of disease. Am J Hematol 2016; 91 (10) 995-1001
4 Newton JL, Reese JA, Watson SI. et al. Fatigue in adult patients with primary immune thrombocytopenia. Eur J Haematol 2011; 86 (05) 420-429
5 White MH, Bennett CM. Fatigue is common in paediatric immune thrombocytopenia and improves with second-line treatments. Br J Haematol 2020; 191 (01) 15-16
6 Kuter DJ, Rummel M, Boccia R. et al. Romiplostim or standard of care in patients with immune thrombocytopenia. N Engl J Med 2010; 363 (20) 1889-1899
7 Cheng G, Saleh MN, Marcher C. et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet 2011; 377 (9763): 393-402
8 Hill QA, Newland AC. Fatigue in immune thrombocytopenia. Br J Haematol 2015; 170 (02) 141-149
9 Grace RF, Klaassen RJ, Shimano KA. et al. Fatigue in children and adolescents with immune thrombocytopenia. Br J Haematol 2020; 191 (01) 98-106
10 George JN, Mathias SD, Go RS. et al. Improved quality of life for romiplostim-treated patients with chronic immune thrombocytopenic purpura: results from two randomized, placebo-controlled trials. Br J Haematol 2009; 144 (03) 409-415
11 Kuter DJ, Mathias SD, Rummel M. et al. Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care. Am J Hematol 2012; 87 (05) 558-561
12 Gudbrandsdottir S, Birgens HS, Frederiksen H. et al. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia. Blood 2013; 121 (11) 1976-1981
13 Van Dijk-Lokkart EM, Steur LMH, Braam KI. et al. Longitudinal development of cancer-related fatigue and physical activity in childhood cancer patients. Pediatr Blood Cancer 2019; 66 (12) e27949
14 Menting J, Nikolaus S, van der Veld WM, Goedendorp MM, Tack CJ, Knoop H. Severe fatigue in type 1 diabetes: Exploring its course, predictors and relationship with HbA_1c in a prospective study. Diabetes Res Clin Pract 2016; 121: 127-134
15 Menting J, Tack CJ, Bleijenberg G. et al. Is fatigue a disease-specific or generic symptom in chronic medical conditions?. Health Psychol 2018; 37 (06) 530-543
16 World Health Organization. The International Classification of Functioning, Disability and Health (ICF). WHO; 2001
17 Nap-van der Vlist MM, Dalmeijer GW, Grootenhuis MA. et al. Fatigue among children with a chronic disease: a cross-sectional study. BMJ Paediatr Open 2021; 5 (01) e000958
18 Stein REK, Jessop DJ. What diagnosis does not tell: the case for a noncategorical approach to chronic illness in childhood. Soc Sci Med 1989; 29 (06) 769-778
19 Matteson KA, Rahn DD, Wheeler II TL. et al; Society of Gynecologic Surgeons Systematic Review Group. Nonsurgical management of heavy menstrual bleeding: a systematic review. Obstet Gynecol 2013; 121 (03) 632-643
20 Menting J, Tack CJ, Donders R, Knoop H. Potential mechanisms involved in the effect of cognitive behavioral therapy on fatigue severity in Type 1 diabetes. J Consult Clin Psychol 2018; 86 (04) 330-340
21 van den Akker LE, Beckerman H, Collette EH. et al; TREFAMS-ACE Study Group. Cognitive behavioral therapy positively affects fatigue in patients with multiple sclerosis: results of a randomized controlled trial. Mult Scler 2017; 23 (11) 1542-1553
22 Menting J, Tack CJ, van Bon AC. et al. Web-based cognitive behavioural therapy blended with face-to-face sessions for chronic fatigue in type 1 diabetes: a multicentre randomised controlled trial. Lancet Diabetes Endocrinol 2017; 5 (06) 448-456
23 van Dijk WEM, Penson A, Kuijlaars IAR. et al. Checklist individual strength to measure severe fatigue in immune thrombocytopenia. Br J Haematol 2022; 197 (03) e41-e44
24 Provan D, Stasi R, Newland AC. et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115 (02) 168-186
25 Vercoulen JH, Alberts M, Bleijenberg G. De Checklist Individual Strength (CIS). Gedragstherapie 1999; 32: 131-136
26 Vercoulen JHMM, Swanink CMA, Fennis JFM, Galama JMD, van der Meer JWM, Bleijenberg G. Dimensional assessment of chronic fatigue syndrome. J Psychosom Res 1994; 38 (05) 383-392
27 Worm-Smeitink M, Gielissen M, Bloot L. et al. The assessment of fatigue: psychometric qualities and norms for the Checklist individual strength. J Psychosom Res 2017; 98: 40-46
28 Dittner AJ, Wessely SC, Brown RG. The assessment of fatigue: a practical guide for clinicians and researchers. J Psychosom Res 2004; 56 (02) 157-170
29 Hewlett S, Dures E, Almeida C. Measures of fatigue: Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF MDQ), Bristol Rheumatoid Arthritis Fatigue Numerical Rating Scales (BRAF NRS) for severity, effect, and coping, Chalder Fatigue Questionnaire (CFQ), Checklist Individual Strength (CIS20R and CIS8R), Fatigue Severity Scale (FSS), Functional Assessment Chronic Illness Therapy (Fatigue) (FACIT-F), Multi-Dimensional Assessment of Fatigue (MAF), Multi-Dimensional Fatigue Inventory (MFI), Pediatric Quality Of Life (PedsQL) Multi-Dimensional Fatigue Scale, Profile of Fatigue (ProF), Short Form 36 Vitality Subscale (SF-36 VT), and Visual Analog Scales (VAS). Arthritis Care Res (Hoboken) 2011; 63 (Suppl. 11) S263-S286
30 Zhou Z, Yang L, Chen Z. et al. Health-related quality of life measured by the Short Form 36 in immune thrombocytopenic purpura: a cross-sectional survey in China. Eur J Haematol 2007; 78 (06) 518-523
31 Rodeghiero F, Michel M, Gernsheimer T. et al. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group. Blood 2013; 121 (14) 2596-2606
32 Kumar M, Dutta S, Bhattyacharyya M. Application of ITP-BAT bleeding score in clinical practice. Int J Hematol 2015; 101 (02) 207-208
33 Webster K, Cella D, Yost K. The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement System: properties, applications, and interpretation. Health Qual Life Outcomes 2003; 1 (01) 79
34 Hewlett S, Chalder T, Choy E. et al. Fatigue in rheumatoid arthritis: time for a conceptual model. Rheumatology (Oxford) 2011; 50 (06) 1004-1006
35 Evers AWM, Kraaimaat FW, van Riel PLCM, de Jong AJL. Tailored cognitive-behavioral therapy in early rheumatoid arthritis for patients at risk: a randomized controlled trial. Pain 2002; 100 (1-2): 141-153
36 van Kessel K, Moss-Morris R, Willoughby E, Chalder T, Johnson MH, Robinson E. A randomized controlled trial of cognitive behavior therapy for multiple sclerosis fatigue. Psychosom Med 2008; 70 (02) 205-213
37 Franek J. Self-management support interventions for persons with chronic disease: an evidence-based analysis. Ont Health Technol Assess Ser 2013; 13 (09) 1-60
38 Vazgiourakis VM, Zervou MI, Eliopoulos E. et al. Implication of VEGFR2 in systemic lupus erythematosus: a combined genetic and structural biological approach. Clin Exp Rheumatol 2013; 31 (01) 97-102
39 Mathias SD, Gao SK, Miller KL. et al. Impact of chronic Immune Thrombocytopenic Purpura (ITP) on health-related quality of life: a conceptual model starting with the patient perspective. Health Qual Life Outcomes 2008; 6 (01) 13
40 Tsukune Y, Komatsu N. Management of adult chronic immune thrombocytopenia in Japan: patient and hematologist perspectives from a multi-center cross-sectional questionnaire survey. Intern Med 2016; 55 (17) 2379-2385
41 Suvajdzic N, Zivkovic R, Djunic I. et al. Health-related quality of life in adult patients with chronic immune thrombocytopenia in Serbia. Platelets 2014; 25 (06) 467-469
42 Trotter P, Hill QA. Immune thrombocytopenia: improving quality of life and patient outcomes. Patient Relat Outcome Meas 2018; 9: 369-384
43 Engel GL. The need for a new medical model: a challenge for biomedicine. Science. 1977; 196 (4286): 129-136
44 van Heukelom RO, Prins JB, Smits MG, Bleijenberg G. Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome and late melatonin secretion. Eur J Neurol 2006; 13 (01) 55-60
45 Castro-Marrero J, Zaragozá MC, López-Vílchez I. et al. Effect of melatonin plus zinc supplementation on fatigue perception in myalgic encephalomyelitis/chronic fatigue syndrome: a randomized, double-blind, placebo-controlled trial. Antioxidants 2021; 10 (07) 1010
46 Lund Rasmussen C, Klee Olsen M, Thit Johnsen A. et al. Effects of melatonin on physical fatigue and other symptoms in patients with advanced cancer receiving palliative care: a double-blind placebo-controlled crossover trial. Cancer 2015; 121 (20) 3727-3736
47 Nguyen MH, Bryant K, O'Neill SG. Vitamin D in SLE: a role in pathogenesis and fatigue? A review of the literature. Lupus 2018; 27 (13) 2003-2011
48 Lassandro G, Carriero F, Palmieri V. et al. Serum vitamin D levels in children with immune thrombocytopenia. Endocr Metab Immune Disord Drug Targets 2020; 20 (02) 221-226
49 Fattizzo B, Zaninoni A, Bianchi P, Fermo E, Nesa F, Barcellini W. 25-OH vitamin D, vitamin D receptor and immunomodulatory cytokines serum levels in patients with autoimmune citopenias: correlation with hematologic parameters and clinical severity. Blood 2014;124(21):
50 Zheng R, Gonzalez A, Yue J. et al. Efficacy and safety of vitamin D supplementation in patients with systemic lupus erythematosus: a meta-analysis of randomized controlled trials. Am J Med Sci 2019; 358 (02) 104-114
51 Liu Z, Doan QV, Blumenthal P, Dubois RW. A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding. Value Health 2007; 10 (03) 183-194
52 Shankar M, Chi C, Kadir RA. Review of quality of life: menorrhagia in women with or without inherited bleeding disorders. Haemophilia 2008; 14 (01) 15-20
53 Berti D, Moons P, Dobbels F, Deuson R, Janssens A, De Geest S. Impact of corticosteroid-related symptoms in patients with immune thrombocytopenic purpura: results of a survey of 985 patients. Clin Ther 2008; 30 (08) 1540-1552
54 Sarpatwari A, Watson S, Erqou S. et al. Health-related lifestyle in adults and children with primary immune thrombocytopenia (ITP). Br J Haematol 2010; 151 (02) 189-191

Zusatzmaterial

Supplementary Material