{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:59:13Z","timestamp":1790189953967,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Immune-mediated thrombotic thrombocytopenic purpura (iTTP) causes systemic microvascular thrombosis, often leading to long-term neurological complications and cognitive decline despite achieving hematologic remission. Persistent blood-brain barrier (BBB) dysfunction is a suspected driver of these chronic sequelae. This study investigated whether adding caplacizumab to standard of care (SOC) improves long-term BBB integrity and cognitive outcomes in refractory iTTP survivors compared with SOC alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      We analyzed 16 patients with iTTP categorized into SOC-only (n=7) or SOC plus caplacizumab (n=9) cohorts. Patients underwent computed tomography perfusion imaging to measure BBB permeability (PS product), blood flow, and blood volume at baseline (30 days postremission) and 12-month follow-up. Cognitive function was assessed using Creyos (URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT03187652).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      At baseline, the caplacizumab group, composed largely of refractory cases, exhibited nominally higher BBB permeability than the SOC-only group (0.48\u00b10.11 mL\/min per 100 grams versus 0.38\u00b10.14 mL\/min per 100 grams,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.048, Cohen d=0.73 [95% CI, \u22120.277 to \u22120.001]), an exploratory finding. The primary outcome, within-group BBB-PS reduction in the SOC plus caplacizumab group at 12 months, was significant (0.37\u00b10.09 mL\/min per 100 grams,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.027, Cohen d=0.90 [95% CI, 0.016\u20130.203]), while the SOC-only group showed minimal change. Despite variations in rituximab administration due to regional funding restrictions, higher BBB permeability was moderately to strongly correlated with lower scores across all cognitive domains and lower ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13) activity (\n                      <jats:italic toggle=\"yes\">q<\/jats:italic>\n                      &lt;0.05, Benjamini-Hochberg corrected).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Caplacizumab may provide a neuroprotective benefit by facilitating BBB repair, even in initially refractory patients. These findings suggest that targeting microvascular integrity during acute episodes can mitigate long-term cognitive decline in iTTP survivors. By facilitating long-term BBB repair, caplacizumab may mitigate chronic cognitive decline and improve the quality of life for refractory iTTP survivors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.126.324382","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T09:01:15Z","timestamp":1778144475000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Neurological Impact of Caplacizumab in Refractory iTTP Survivors: A Comparative Study of Blood-Brain-Barrier Integrity and Cognitive Outcomes"],"prefix":"10.1161","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8321-683X","authenticated-orcid":true,"given":"Fahad","family":"Hannan","sequence":"first","affiliation":[{"name":"Department of Medical Biophysics (F.H., J.D.T., J.T., S.-H.S.H.), Schulich School of Medicine and Dentistry, Western University, London, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6132-3020","authenticated-orcid":true,"given":"Jonathan D.","family":"Thiessen","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics (F.H., J.D.T., J.T., S.-H.S.H.), Schulich School of Medicine and Dentistry, Western University, London, Canada."},{"name":"Division of Medical Physics, CancerCare Manitoba, Winnipeg, Canada (J.D.T.)."},{"name":"Department of Radiology, University of Manitoba, Winnipeg, Canada (J.D.T.)."},{"name":"Lawson Imaging, Lawson Health Research Institute, London, Canada (J.D.T., T.-Y.L., J.T., S.-H.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2089-8650","authenticated-orcid":true,"given":"Christopher J.","family":"Patriquin","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology &amp; Hematology, University Health Network, Toronto, Canada (C.J.P.)."},{"name":"Department of Medicine (Hematology) (C.J.P.), University of Toronto, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-5197","authenticated-orcid":true,"given":"Katerina","family":"Pavenski","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Laboratory Medicine &amp; Pathobiology (K.P.), University of Toronto, Canada."},{"name":"Departments of Medicine and Laboratory Medicine, St. Michael\u2019s Hospital\u2014Unity Health Toronto, Canada (K.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro","family":"Tristao","sequence":"additional","affiliation":[{"name":"Department of Radiology, McMaster University, Hamilton, Canada (J.L.M., L.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7605-9752","authenticated-orcid":true,"given":"Ting-Yim","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging (T.-Y.L., J.T.), Schulich School of Medicine and Dentistry, Western University, London, Canada."},{"name":"Lawson Imaging, Lawson Health Research Institute, London, Canada (J.D.T., T.-Y.L., J.T., S.-H.S.H.)."},{"name":"Robarts Research Institute, London, Canada (T.-Y.L., D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Mendes","sequence":"additional","affiliation":[{"name":"Robarts Research Institute, London, Canada (T.-Y.L., D.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7578-4469","authenticated-orcid":true,"given":"Jean","family":"Th\u00e9berge","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics (F.H., J.D.T., J.T., S.-H.S.H.), Schulich School of Medicine and Dentistry, Western University, London, Canada."},{"name":"Department of Medical Imaging (T.-Y.L., J.T.), Schulich School of Medicine and Dentistry, Western University, London, Canada."},{"name":"Lawson Imaging, Lawson Health Research Institute, London, Canada (J.D.T., T.-Y.L., J.T., S.-H.S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1331-0695","authenticated-orcid":true,"given":"Jennifer L.","family":"Mandzia","sequence":"additional","affiliation":[{"name":"Department of Radiology, McMaster University, Hamilton, Canada (J.L.M., L.T.)."},{"name":"Department of Clinical Neurological Sciences, Western University, London, Canada (J.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Al-Jaishi","sequence":"additional","affiliation":[{"name":"London Health Sciences Research Institute, Canada (M.A.-J., K.L.G., 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