Blood–brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder of systemic microthrombosis and organ ischemia. The etiology of chronic cerebrovascular outcomes in iTTP survivors is largely unknown. In this pilot study, we measured blood–brain barrier (BBB) permeabili...

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Autores principales: Huang, Shih-Han Susan, Pavenski, Katerina, Lee, Ting-Yim, Jurkiewicz, Michael T., Bharatha, Aditya, Thiessen, Jonathan Dale, St. Lawrence, Keith, Théberge, Jean, Mandzia, Jennifer, Barth, David, Licht, Christoph, Patriquin, Christopher Jordan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Hematology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945621/
https://www.ncbi.nlm.nih.gov/pubmed/34521110
http://dx.doi.org/10.1182/bloodadvances.2021005317
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author Huang, Shih-Han Susan
Pavenski, Katerina
Lee, Ting-Yim
Jurkiewicz, Michael T.
Bharatha, Aditya
Thiessen, Jonathan Dale
St. Lawrence, Keith
Théberge, Jean
Mandzia, Jennifer
Barth, David
Licht, Christoph
Patriquin, Christopher Jordan
author_facet Huang, Shih-Han Susan
Pavenski, Katerina
Lee, Ting-Yim
Jurkiewicz, Michael T.
Bharatha, Aditya
Thiessen, Jonathan Dale
St. Lawrence, Keith
Théberge, Jean
Mandzia, Jennifer
Barth, David
Licht, Christoph
Patriquin, Christopher Jordan
author_sort Huang, Shih-Han Susan
collection PubMed
description Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder of systemic microthrombosis and organ ischemia. The etiology of chronic cerebrovascular outcomes in iTTP survivors is largely unknown. In this pilot study, we measured blood–brain barrier (BBB) permeability in patients with iTTP at the start of remission and 6 months later. This prospective pilot study included 7 adult patients with incident iTTP. Eligibility criteria included ADAMTS13 activity < 10% and detectable inhibitor at diagnosis. Patients were recruited from London Health Sciences Centre in Canada (2017-2019) within 3 days of hospital admission and followed for 6 months after remission (defined as normalization of platelet count and lactate dehydrogenase with no clinical signs or symptoms of microvascular injury for more than 30 days after the last plasma exchange). All patients had cerebral computed tomography perfusion scans with BBB permeability surface product measurements. Patients (5 women, 2 men) had a mean age of 48 years (range, 21-77 years). At diagnosis, patients had a mean platelet count of 22 (standard deviation [SD], 25) × 10(9)/L. At the start of remission, mean BBB permeability surface product was 0.91 (0.30) mL/min/100 g. Six months later, the mean permeability surface product was 0.56 (0.22) mL/min/100 g, with a mean difference of −0.312 mL/min/100 g (95% confidence interval: −0.4729 to −0.1510; P = .0032). In this pilot study of patients with iTTP, pathologically increased BBB permeability was evident, and although there was some improvement, this persisted 6 months after remission. Future work will explore the chronicity of these findings and their clinical implications.
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spelling pubmed-89456212022-03-29 Blood–brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study Huang, Shih-Han Susan Pavenski, Katerina Lee, Ting-Yim Jurkiewicz, Michael T. Bharatha, Aditya Thiessen, Jonathan Dale St. Lawrence, Keith Théberge, Jean Mandzia, Jennifer Barth, David Licht, Christoph Patriquin, Christopher Jordan Blood Adv Platelets and Thrombopoiesis Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder of systemic microthrombosis and organ ischemia. The etiology of chronic cerebrovascular outcomes in iTTP survivors is largely unknown. In this pilot study, we measured blood–brain barrier (BBB) permeability in patients with iTTP at the start of remission and 6 months later. This prospective pilot study included 7 adult patients with incident iTTP. Eligibility criteria included ADAMTS13 activity < 10% and detectable inhibitor at diagnosis. Patients were recruited from London Health Sciences Centre in Canada (2017-2019) within 3 days of hospital admission and followed for 6 months after remission (defined as normalization of platelet count and lactate dehydrogenase with no clinical signs or symptoms of microvascular injury for more than 30 days after the last plasma exchange). All patients had cerebral computed tomography perfusion scans with BBB permeability surface product measurements. Patients (5 women, 2 men) had a mean age of 48 years (range, 21-77 years). At diagnosis, patients had a mean platelet count of 22 (standard deviation [SD], 25) × 10(9)/L. At the start of remission, mean BBB permeability surface product was 0.91 (0.30) mL/min/100 g. Six months later, the mean permeability surface product was 0.56 (0.22) mL/min/100 g, with a mean difference of −0.312 mL/min/100 g (95% confidence interval: −0.4729 to −0.1510; P = .0032). In this pilot study of patients with iTTP, pathologically increased BBB permeability was evident, and although there was some improvement, this persisted 6 months after remission. Future work will explore the chronicity of these findings and their clinical implications. American Society of Hematology 2021-10-22 /pmc/articles/PMC8945621/ /pubmed/34521110 http://dx.doi.org/10.1182/bloodadvances.2021005317 Text en © 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
spellingShingle Platelets and Thrombopoiesis
Huang, Shih-Han Susan
Pavenski, Katerina
Lee, Ting-Yim
Jurkiewicz, Michael T.
Bharatha, Aditya
Thiessen, Jonathan Dale
St. Lawrence, Keith
Théberge, Jean
Mandzia, Jennifer
Barth, David
Licht, Christoph
Patriquin, Christopher Jordan
Blood–brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study
title Blood–brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study
title_full Blood–brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study
title_fullStr Blood–brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study
title_full_unstemmed Blood–brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study
title_short Blood–brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study
title_sort blood–brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study
topic Platelets and Thrombopoiesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945621/
https://www.ncbi.nlm.nih.gov/pubmed/34521110
http://dx.doi.org/10.1182/bloodadvances.2021005317
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