Silent cerebral infarction during immune TTP remission: prevalence, predictors, and impact on cognition.

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Immune thrombotic thrombocytopenic purpura (iTTP) survivors have increased risk of cardiovascular disease, including strokes, and report persistent cognitive difficulties during remission. We conducted this prospective study involving iTTP survivors during clinical remission to determine the prevalence of silent cerebral infarction (SCI), defined as magnetic resonance imaging (MRI) evidence of brain infarction without corresponding overt neurodeficits. We also tested the hypothesis that SCI is associated with cognitive impairment, assessed using the National Institutes of Health ToolBox Cognition Battery. For cognitive assessments, we used fully corrected T scores adjusted for age, sex, race, and education. Based on the diagnostic and statistical manual 5 criteria, we defined mild and major cognitive impairment as T scores with a 1 or 2 standard deviation (SD) and >2 SD below the mean on at least 1 test, respectively. Forty-two patients were enrolled, with 36 completing MRIs. SCI was present in 50% of the patients (18), of which 8 (44.4%) had prior overt stroke including during acute iTTP. Patients with SCI had higher rates of cognitive impairment (66.7% vs 27.7%; P = .026), including major cognitive impairment (50% vs 5.6%; P = .010). In separate logistic regression models, SCI was associated with any (mild or major) cognitive impairment (odds ratio [OR] 10.5 [95% confidence interval (95% CI), 1.45-76.63]; P = .020) and major cognitive impairment (OR 7.98 [95% CI, 1.11-57.27]; P = .039) after adjusting for history of stroke and Beck depression inventory scores. MRI evidence of brain infarction is common in iTTP survivors; the strong association of SCI with impaired cognition suggests that these silent infarcts are neither silent nor innocuous.


This work was supported by National Institutes of Health (NIH), National Heart, Lung, and Blood Institute grant K99HL150594 (S.C.) and an American Society of Hematology Scholar Award (S.C.). R.F.G. is supported by the NIH National Institute for Neurological Disorders and Stroke intramural research program.

Conflict-of-interest disclosure: S.C. is on advisory boards and provides consultancy for Alexion, Sanofi, UCB, Sobi, and Takeda; and reports honoraria/royalties from UpToDate and Dynamed. S.M.L. provides consultancy for Bluebird bio, Novo Nordisk, Pfizer, Novartis, and Magenta; reports honoraria from Novartis; reports research funding from Imara, Novartis, GBT, Takeda, CSL Behring, HRSA, PCORI, and MD CHRC; and reports stocks in Pfizer and Teva. R.P.N. provides consultancy for Elsevier. A.R.M. is on the advisory board of PharmEssentia. M.B.S. provides consultancy for CSL Behring, Johnson & Johnson, and Pfizer; is a member of data safety monitoring board of CSL Behring; receives funding from AHRQ, NovoNordisk, PCORI, Sanofi, and Tremeau; and receives honoraria from Pfizer. The remaining authors declare no competing financial interests.



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