Documentation of Fatigue In Patients with Immune Thrombocytopenic Purpura (ITP) and Its Association with Autonomic Dysfunction
Authors: Reese Jessica A , Newton Julia , Watson Shirley , Vesely Sara K. , Bolton-Maggs Paula , George James N. , Terrell Deirdra 
Published: October 2019

Abstract
Abstract 570
Bleeding is the characteristic symptom of ITP but recent data from development of quality-of-life questionnaires have suggested that fatigue may be a common problem. Previous studies of another autoimmune disease, primary biliary cirrhosis, have documented that fatigue is common and is associated with autonomic nervous system dysfunction and daytime sleepiness (Hepatology 2007;45:1496). The goals of this study were to survey adult patients with ITP to [1] estimate the prevalence of fatigue among ITP patients, [2] describe characteristics of ITP that are related to the occurrence of fatigue, and [3] determine if fatigue in ITP, as in primary biliary cirrhosis, may be associated with autonomic dysfunction manifested by orthostatic symptoms and excessive daytime sleepiness. The survey contained questions about ITP, bleeding symptoms, and symptoms of fatigue that were developed specifically for this study together with established, validated questionnaires that quantitatively score symptoms of fatigue (Fatigue Impact Scale [FIS]), symptoms of autonomic dysfunction (Orthostatic Grading Scale [OGS]), and symptoms of daytime sleepiness (Epworth Sleepiness Scale [ESS]). 585 (31%) of 1871 members of the UK ITP Support Association and 69 (74%) of 93 patients in the Oklahoma ITP Registry completed and returned their surveys. Both groups of patients were combined for our analysis. 68% of patients had had ITP for ≥5 years; 31% had had a splenectomy; 63% had active ITP defined by a platelet count <100,000/μ L and/or current treatment for ITP; 17% reported that they had bleeding problems daily/weekly/monthly (described as “bleeding”) vs. rarely/never (described as no bleeding). 63% had other diagnosed medical conditions. 78% of patients reported that their energy levels had changed since having ITP and 67% reported that they had less energy when their platelet count is low. Fatigue (FIS≥40) was present for 37% of patients. Odds ratios (OR) with 95% confidence intervals were calculated using logistic regression to estimate the association between fatigue (FIS≥40) and other variables while controlling for confounders. A multivariate model was created and active ITP, bleeding, other medical conditions, OGS≥4, and ESS≥10 were all independently associated with fatigue (P<0.05). Country was included in the model, even though it was not independently associated with fatigue. The data were then stratified by bleeding status, because interactions between bleeding and active ITP (P=0.034) and bleeding and ESS (P=0.026) were significant.VariableStratified OR (95% CI), Bleeding (n=105)Stratified OR(95% CI), No bleeding (n=490)Active ITP (Yes vs. No)4.64 (1.58, 13.63)1.27 (0.79, 2.02)Other medical conditions (Yes vs. No)1.14 (0.45, 2.91)1.76 (1.09, 2.84)OGS (≥4 vs. <4)3.09 (1.21, 7.93)4.76 (2.98, 7.60)ESS (≥10 vs. <10)1.93 (0.78, 4.77)5.51 (3.50, 8.66)Country (UK vs. US)0.37 (0.05, 2.62)0.59 (0.27, 1.28)
Among patients who report bleeding problems, having active ITP and having a high OGS (≥4) remain independently associated with fatigue. Among patients with no bleeding, having other medical conditions, a high OGS (≥4), and a high ESS (≥10) are independently associated with fatigue.

Conclusion:
Patients with ITP frequently report energy changes that appear to be greater when their platelet count is lower. In this analysis, we document that fatigue is associated with bleeding problems and that predictors of fatigue are different among patients with and without bleeding problems. Fatigue is associated with orthostatic symptoms in patients with and without bleeding problems. Fatigue is associated with active ITP only in patients with bleeding problems; fatigue is associated with other medical conditions and sleepiness symptoms only in patients without bleeding problems. The association of orthostatic and sleepiness symptoms with fatigue in patients with ITP suggests that the fatigue symptoms may be related to autoimmune autonomic abnormalities.

Disclosures:
No relevant conflicts of interest to declare.