Identification of an Unmet Medical Need – Height of Depression, Hypersomnia and Sleep Apnea Positively Correlate with the Level of Fatigue in Patients with Immune Thrombocytopenia

Introduction Immune thrombocytopenia (ITP) is a rare chronic disease, frequently accompanied by fatigue, which is an important comorbidity associated with this disease [1]. Patients experience difficulties to manage their daily activities and a reduction in their overall quality of life (QoL) [2]. The causes of fatigue in ITP are not clarified yet and underlying causes seem to be multifactorial. The development of fatigue may not solely be influenced by a decrease in platelet count, but also by unknown factors as well as psychological reasons [3] [4].

Method This prospective, multicenter, exploratory, pilot study aimed to investigate which parameters contribute to the occurrence of fatigue in patients with ITP. Adult patients with ITP and with or without fatigue, who visited the study center for their regular appointments were asked to complete questionnaires pertaining to patient-reported outcome measures regarding depression, sleep apnea and hypersomnia and the ISTH-BAT. Blood tests included platelet count as well as different parameters like vitamin D ([Fig. 1]).

Fig. 1 Internal consistency of total score, trial outcome index, and subscales (FAS); BDI: Beck Depression Inventory; FACIT‑F: Functional Assessment of Chronic Illness Therapy–Fatigue; FAS: full-analysis set; ISTH/SSC: International Society on Thrombosis and Haemostasis/Scientific and Standardization Committee; n: number; OSAS: obstructive sleeping apnea syndrome; SD: standard deviation; STOP-BANG: snore, tired, observed apneas, pressure, body mass index, age, neck circumference, gender

Results A total of 36 patients (27 females, nine males) with primary ITP, with a median age of 46.5 years (min‑max 19‑83) were analyzed. Median duration of ITP was 4.5 years (min‑max 0-21). Approximately one-third of patients (29.4%) had no comorbidities.The two most frequently used current treatment options were ‘watch-and-wait’ (38.9%) and thrombopoietin-receptor-agonists (58.3%); eight patients needed rescue therapy. There was a statistically negative correlation between fatigue and year of diagnosis (r=-0.41, p=0.014). Results indicated no statistically significant relationship in fatigue and age or gender. Ferritin predicted fatigue with statistical significance while platelet count was not correlated. A significant correlation was obvious between fatigue, depression and obstructive sleep apnea syndrome as well as sleep-related problems (p<0.01).

Conclusion Patient characteristics were comparable to that of other studies [1] [2] [3] [4]. The level of fatigue negatively impacts the lives of patients with ITP. Age and gender were not correlated with fatigue in ITP, which is in line with other reports. Interestingly, the fatigue level was higher in patients presenting with an additional depression and poor sleeping quality due to, e.g., hypersomnia, which seems not uncommon [5]. Fatigue levels seem independent from thrombocyte levels, which was reported elsewhere [3].

Patients diagnosed with ITP several years ago cope with their condition better than patients with a more recent diagnosis, who have higher levels of fatigue. Concurrent depression, hypersomnia and sleep apnea are important underestimated factors, which do have a negative effect on the QoL of patients with ITP. We were able to show that patients with ITP might face an unmet medical need in terms of delayed diagnosis and supportive therapy. To our knowledge this is the first report on combined findings of depression, hypersomnia and sleep apnea in patients with ITP.

Publication History

Article published online:
26 February 2024

• References

• 1 Matzdorff A, Alesci SR, Gebhart J. et al. Expert Report on Immune Thrombocytopenia: Current Diagnostics and Treatment – Recommendations from an Expert Group from Austria, Germany, and Switzerland. Oncol Res Treat 2023; 46 (Suppl. 02) 5-44 DOI: 10.1159/000529662..
• 2 Hill QA, Newland AC. Fatigue in immune thrombocytopenia. Br J Haematol 2015; 170: 141-149 DOI: 10.1111/bjh.13385..
• 3 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: 188-198 DOI: 10.1002/ajh.26045..
• 4 Newton JL, Reese JA, Watson SI. et al. Fatigue in adult patients with primary immune thrombocytopenia. Eur J Haematol 2011; 86: 420-429 DOI: 10.1111/j.1600-0609.2011.01587.x..
• 5 Farney RJ, Walker BS, Farney RM, Snow GL, Walker JM. The STOP-Bang equivalent model and prediction of severity of obstructive sleep apnea: relation to polysomnographic measurements of the apnea/hypopnea index. J Clin Sleep Med 2011; 7: 459-465b DOI: 10.5664/jcsm.1306..