Neurocognitive Impairment Following Recovery from ADAMTS13-Deficient Thrombotic Thrombocytopenia Purpura (TTP).
Authors: Lewis Qurana F. , Scott James G. , Hovinga Johanna A. Kremer , Lämmle Bernhard , Terrell Deirdra R. , Vesely Sara K. , George James N. 
Published: October 2019

Patients who survive an acute episode of TTP often describe persistent problems with concentration, memory and fatigue in spite of continued remission. To assess these symptoms, we performed neuropsychological tests assessing 11 cognitive domains. We hypothesized that domains assessing complex attention/concentration skills and high level memory functions would be affected because these are characteristically abnormal in disorders with diffuse microvascular subcortical lesions. The Oklahoma TTP-HUS Registry enrolled 247 consecutive patients with their first episode of clinically diagnosed TTP from 11-13-1995 (the date of our initial ADAMTS13 measurement) to 6-30-2006; ADAMTS13 activity was measured in 228 (92%) patients immediately before their first plasma exchange treatment; 42 (18%) patients had ADAMTS13 activity <10%; 31 were currently alive; 25 (81%) were included in this study (3 patients were excluded because of dementia, 1 was too young to be evaluated, 1 was incarcerated, 1 was lost to follow-up). 21 (84%) patients were women; 9 (36%) were black; median age was 44 years (range 20–64); median time since their last episode was 46 months (range 2–127). At the time of the evaluation physical examinations and the Mini-Mental State Exams were normal. Median hematocrit was 39% (range 31–51%, 1 women had iron deficiency). Median platelet count was 303 (range 81–518; 1 woman has had persistent mild thrombocytopenia). ADAMTS13 levels remained <10% in 4 patients and were 10–20% in 4 additional patients. Results from the neuropsychological tests were compared to normal population values matched for age and education level and converted to a score with a mean value of 0 and a standard deviation of 1.

Neurocognitive test domain Patients mildly impaired* Mean score P (score) *Patients were categorized as mildly impaired if they scored ≥ 1 standard deviation below the mean (≤16th percentile). List learning 9 (36%) −0.85 0.001 Manual dexterity 10 (40%) −0.65 0.006 Complex attention, sequencing 7 (28%) −0.61 0.003 Rapid language generation 8 (32%) −0.46 0.013

The 25 patients as a group performed significantly worse than the population norms for 4 of the 11 domains. 18 (72%) patients were mildly impaired on 1 or more of these 4 domains; 10 of these patients had no severe neurologic abnormalities (seizure, stroke, coma, focal signs) during their acute episode. These are the 4 domains that are expected to be abnormal in patients with diffuse microvascular subcortical lesions. For the 7 other domains that are expected to be unaffected in these patients, our patients did not perform worse than the normal population: general cognitive functioning, visual perceptual skills, simple sustained attention, simple reaction time, executive function, semantic and visual memory.

Conclusions:

Patients who appear to have a complete recovery from their acute episode of TTP may have persistent neurocognitive abnormalities, causing deficits of attention, processing speed, and memory, slower motor function and fatigue. The pattern of neurocognitive abnormalities is similar to patients with other diffuse microvascular or thrombotic abnormalities, such as sickle cell anemia. Awareness of these potential problems is important to provide appropriate support.