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

Abstract

Introduction: Immune thrombocytopenia (ITP) is a rare chronic disease, frequently accompanied by fatigue, which is an important comorbidity associated with this disease. Patients experience difficulties in managing their daily activities and a reduction in their overall quality of life (QoL). 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.

Methods: 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 bleeding symptoms, depression, sleep apnea, and hypersomnia. Blood tests included platelet count as well as different parameters like vitamin D.

Results: A total of 36 patients (100%; 27 females (75%) and nine males (25%)) with primary ITP, with a median age of 46.5 years (range 19‑83 years) were analyzed. The median duration of ITP was 4.5 years (min‑max 0-21). Approximately one-third of patients (29.4%; 10/34 patients) had no comorbidities. The two most frequently used current treatment options were "watch-and-wait" (38.9%; 14/36 patients) and "avatrombopag" (30.6%; 11/36 patients); eight patients (22.2%; 8/36 patients) needed rescue therapy with corticosteroids. There was a statistically negative correlation between fatigue and year of diagnosis (r=-0.41, p=0.014). Results indicated no statistically significant relationship between fatigue and age or differences in fatigue between the genders. Ferritin predicted fatigue with statistical significance. Platelet count was not correlated with the level of fatigue. A significant correlation was obvious between fatigue, depression, and obstructive sleep apnea syndrome (OSAS) as well as sleep-related problems (p<0.01).

Discussion: Patient characteristics were comparable to that of other studies. 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 additional depression and poor sleeping quality due to, e.g., hypersomnia, which seems common. Fatigue levels seem independent from thrombocyte levels, which were reported elsewhere.

Conclusion: 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.