Fatigue and Cognition During Remission in Adults with Immune Thrombotic Thrombocytopenic Purpura

Introduction: Although impaired cognitive function following recovery from immune-mediated thrombotic thrombocytopenic purpura (iTTP) has been well-described, the issue of fatigue is rarely addressed. In our qualitative studies, people with iTTP described fatigue significantly impacted their daily lives. It is unknown if the prevalence of fatigue in iTTP patients differs from the general population. The first aim of this study was to compare fatigue and cognitive scores of people with iTTP in clinical remission to both the United States (US) population and to people with other disorders. Our second aim was to describe clinical severity of fatigue and cognitive impairment among people with iTTP in remission.

Methods: Patients were recruited from 9 US centers (8/2019 - 11/2021). Eligibility included: 1) age >18 years, 2) ADAMTS13 deficiency (<10% activity) at diagnosis or during a relapse and 3) being >1-year from the last episode. Fatigue and cognitive function were assessed with the validated NIH Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROMIS measures are disease cross-cutting instruments which allow for comparisons to not only the US population but also other disorders. Demographic information was also obtained.

A one sample t-test was used to compare mean fatigue score of iTTP patients to the US population. iTTP patients were compared to other disorders using PROMIS mean scores and 95% confidence intervals (CI). To aid in clinical interpretation of PROMIS scores, severity thresholds (‘No/Mild’, ‘Moderate’, ‘Severe’) were created utilizing T-score ranges as described previously (Terrell DR, et al Blood 2021; 834). Patients were compared by severity categories and clinical characteristics.

Results: 101 patients completed the study (83% female; 52% White; 36% Black; median age 49.5 years [range 26-85 years]). The mean fatigue score in the iTTP patients was 58 (95% CI 56.4, 60.3), significantly worse than the US population (mean 50), (p<0.0001) with higher scores indicating worse function. Comparisons to other disorders indicated that fatigue in iTTP patients was worse than breast cancer survivors and persons who had recovered from severe COVID-19, but similar to patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (Figure 1). The mean cognitive function score in iTTP patients was 45 (95% CI 43.2, 46.8), significantly worse than the US population (p<0.0001) with lower scores indicating worse function. iTTP cognitive function was worse than breast cancer patients and persons who have recovered from severe COVID-19, but similar to patients with SLE (Figure 1).

Table 1 shows the overlap of clinical severity for cognitive and fatigue symptoms. 13% (13/101) of patients in remission had scores indicating ‘Severe’ impairment on both domains (cognitive and fatigue). Notably, the majority (62%) of patients with severe impairment on both measures were > 5 years since their last episode while only 38% had experienced a relapse. In contrast, 36% of patients with ‘No/Mild’ impairment on both measures were > 5 years from their last episode and 50% of them had relapsed. Yet, patients with moderate severity on both measures were the most likely to report surviving a relapse (68%) and 50% of these patients were > 5 years from their most recent episode.

Conclusion: Fatigue and cognitive function in iTTP patients is worse than the US population but similar to chronic autoimmune disorders such as SLE. Further, 62% of people with severe impairment on both fatigue and cognitive measures were more than 5-years from their most recent episode, and a history of disease relapse was not associated with more severe symptoms. These data suggest that even in long-term ‘remission’, people with iTTP continue to struggle with severe fatigue and cognition, and whether this relates to the initial disease occurrence or continued sub-clinical disease activity is unknown. Strengths of this study included the large number of patients that were recruited from 9 US academic centers. Future studies should evaluate the impact of ADAMTS13 activity and subclinical microangiopathy on symptom clinical severity.