{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T04:28:59Z","timestamp":1772771339328,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Answering TTP Foundation","award":["T32 HL007093"],"award-info":[{"award-number":["T32 HL007093"]}]},{"name":"Answering TTP Foundation","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}]},{"name":"Answering TTP Foundation","award":["UM1TR004405"],"award-info":[{"award-number":["UM1TR004405"]}]},{"name":"Answering TTP Foundation","award":["1K01HL135466"],"award-info":[{"award-number":["1K01HL135466"]}]},{"name":"National Institutes of Health","award":["T32 HL007093"],"award-info":[{"award-number":["T32 HL007093"]}]},{"name":"National Institutes of Health","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}]},{"name":"National Institutes of Health","award":["UM1TR004405"],"award-info":[{"award-number":["UM1TR004405"]}]},{"name":"National Institutes of Health","award":["1K01HL135466"],"award-info":[{"award-number":["1K01HL135466"]}]},{"name":"National Heart, Lung, and Blood Institute","award":["T32 HL007093"],"award-info":[{"award-number":["T32 HL007093"]}]},{"name":"National Heart, Lung, and Blood Institute","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}]},{"name":"National Heart, Lung, and Blood Institute","award":["UM1TR004405"],"award-info":[{"award-number":["UM1TR004405"]}]},{"name":"National Heart, Lung, and Blood Institute","award":["1K01HL135466"],"award-info":[{"award-number":["1K01HL135466"]}]},{"name":"National Institutes of Health\u2019s National Center for Advancing Translational Sciences","award":["T32 HL007093"],"award-info":[{"award-number":["T32 HL007093"]}]},{"name":"National Institutes of Health\u2019s National Center for Advancing Translational Sciences","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}]},{"name":"National Institutes of Health\u2019s National Center for Advancing Translational Sciences","award":["UM1TR004405"],"award-info":[{"award-number":["UM1TR004405"]}]},{"name":"National Institutes of Health\u2019s National Center for Advancing Translational Sciences","award":["1K01HL135466"],"award-info":[{"award-number":["1K01HL135466"]}]},{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["T32 HL007093"],"award-info":[{"award-number":["T32 HL007093"]}]},{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}]},{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["UM1TR004405"],"award-info":[{"award-number":["UM1TR004405"]}]},{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["1K01HL135466"],"award-info":[{"award-number":["1K01HL135466"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, chronically relapsing disorder that causes life-threatening thrombotic microangiopathy. Many survivors in clinical remission show evidence of ongoing silent cerebral infarction and neurocognitive deficits. Prospective longitudinal studies of this population are needed to acquire a complete understanding of the mechanism behind this ongoing neurologic injury. We aimed to assess the feasibility of a multicenter prospective study of neuropsychological and cognitive function in iTTP survivors in remission and examine novel biomarkers. Methods: We aimed to enroll 50 iTTP patients across three USTMA consortium sites between 2019 and 2022 in a 24-month longitudinal study. Clinical, cognitive, and biomarker assessments, including ADAMTS13 activity, were performed. Results: Despite the COVID-19 pandemic, we enrolled 38 subjects, and 31 (81.6%) completed closeout evaluations at 24 months. Upon the participants\u2019 enrollment in the study, we confirmed previous findings, including high rates of moderate to severe neurocognitive and psychiatric sequelae (anxiety, 47%; depression, 45%; and headaches, 55%). Changes in cognitive function were measurable and included decreased immediate memory and visuospatial abilities. Over this two-year study, we did not see a significant change in neurocognitive findings. There was no association between cognitive function and ADAMTS13 activity; however, we found that the level of soluble thrombomodulin (CD141) was significantly correlated with cognitive impairment. Conclusions: We conclude that a more extensive study is feasible, and at least 5\u201310 years may be required to detect trends in neurocognitive function. Soluble thrombomodulin is a promising biomarker for cognitive impairment in survivors of iTTP, and it is worthy of additional study.<\/jats:p>","DOI":"10.3390\/jcm14030694","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T05:50:53Z","timestamp":1737525053000},"page":"694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Multicenter Prospective Pilot Study Identifying Thrombomodulin as a Potential Biomarker for Neurocognitive Outcomes in Immune Thrombotic Thrombocytopenic Purpura"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9566-7809","authenticated-orcid":false,"given":"Aaron B.","family":"Boothby","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7449-3993","authenticated-orcid":false,"given":"Michael D.","family":"Evans","sequence":"additional","affiliation":[{"name":"Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangbin","family":"Yang","sequence":"additional","affiliation":[{"name":"Section of Hematology-Oncology, Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0882-6793","authenticated-orcid":false,"given":"Senthil","family":"Sukumar","sequence":"additional","affiliation":[{"name":"Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James G.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0794-5851","authenticated-orcid":false,"given":"Deirdra R.","family":"Terrell","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8977-6910","authenticated-orcid":false,"given":"Spero","family":"Cataland","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Ohio State University, Columbus, OH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-3069","authenticated-orcid":false,"given":"Marshall","family":"Mazepa","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2839","DOI":"10.1182\/blood.V91.8.2839.2839_2839_2846","article-title":"Acquired deficiency of von Willebrand factor-cleaving protease in a patient with thrombotic thrombocytopenic purpura","volume":"91","author":"Furlan","year":"1998","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1056\/NEJM199811263392203","article-title":"Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura","volume":"339","author":"Tsai","year":"1998","journal-title":"N. 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