Poor responder to plasma exchange therapy in acquired thrombotic thrombocytopenic purpura is associated with ADAMTS13 inhibitor boosting: visualization of an ADAMTS13 inhibitor complex and its proteolytic clearance from plasma.

• Material Type: 博士論文
• Title: Poor responder to plasma exchange therapy in acquired thrombotic thrombocytopenic purpura is associated with ADAMTS13 inhibitor boosting: visualization of an ADAMTS13 inhibitor complex and its proteolytic clearance from plasma.
• Author/Editor: Isonishi, Ayami; Bennett, Charles L.; Plaimauer, Barbara; Scheiflinger, Friedrich; Matsumoto, Masanori; Fujimura, Yoshihiro
• Author Heading: Isonishi, Ayami; Bennett, Charles L.; Plaimauer, Barbara; Scheiflinger, Friedrich; Matsumoto, Masanori; Fujimura, Yoshihiro
• Publication, Distribution, etc.: American Association Of Blood Banks / John Wiley & Sons, Inc.
• Publication Date: 2015-10
• Publication Date (W3CDTF): 2015-10
• Alternative Title: 後天性血栓性血小板減少性紫斑病治療における血漿交換不応例は、ADAMTS13インヒピター力価の急上昇によって発生する : 治療中の患者血漿中ADAMTS13抗原抗体複合体の動態可視化
• Periodical title: Transfusion
• No. or year of volume/issue: 55 10
• Volume: 55
• Issue: 10
• Pages: 2321-2330
• ISSN (Periodical Title): ISSN : 0041-1132
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2017-11-24
• Dissertation Number: 乙第1412号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: FFP Transfusion; Immune Thrombocytopenia
• Target Audience: 一般
• Note (General): type:Thesis; BACKGROUND: Plasma exchange (PE) is the first-line treatment for primary acquired thrombotic thrombocytopenic purpura (aTTP) with severe deficiency of ADAMTS13 activity (ADAMTS13:AC). Some patients are poor responders to PE, raising concern over multiple pathogenetic pathways. STUDY DESIGN AND METHODS: Based on 52 aTTP patients in our national cohort study, we monitored plasma levels of ADAMTS13, clinical and laboratory findings, and outcomes. In a representative poor responder to PE, we examined an ADAMTS13 inhibitor (ADAMTS13:INH) complex in plasma milieu, by means of a large-pore isoelectric focusing (IEF) analysis. RESULTS: Of 52 aTTP patients, 20 were good responders and 32 were poor responders. In the latter group, plasma ADAMTS13:AC levels never increased to more than 10% of normal during 14 days after PE initiation. Mean (±SD) plasma ADAMTS13:INH titers (Bethesda unit/mL) were 5.7 (±4.5) before PE, but decreased to 1.4 (±0.8) on the fourth PE day and then remarkably increased to 14.8 (±10.0) on the 10th PE day, termed "inhibitor boosting," and then slowly decreased to undetectable level over 1 month. On admission, none of the routinely available clinical and laboratory markers differentiated these two groups. However, elevated pre-PE levels of ADAMTS13:INH were correlated with a poor response. We visualized an ADAMTS13:INH (immunoglobulin G) complex in a patient plasma by an IEF analysis and found proteolytic fragment of ADAMTS13 antigen by a two-dimensional IEF and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. CONCLUSION: Findings from this cohort of aTTP patients demonstrated that inhibitor boosting often occurs in aTTP patients in Japan. Poor responders could be predicted by elevated pre-PE ADAMTS13:INH levels on admission, but not by routinely collected clinical or laboratory data.; 博士（医学）・乙第1412号・平成29年11月24日; © 2015 AABB(American Association Of Blood Banks); Copyright © 1999 - 2017 John Wiley & Sons, Inc. All Rights Reserved; This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/trf.13182], which has been published in final form at [http://dx.doi.org/10.1111/trf.13182]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.; identifier:Transfusion Vol.55 No.10 p.2321-2330 (2015 Oct); identifier:00411132; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3393; identifier:Transfusion, 55(10): 2321-2330
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1111/trf.13182
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

Table of Contents

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3393/1/01%e4%b9%991412%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3393/2/02%e4%b9%991412%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3393/6/03%e4%b9%991412%e6%9c%ac%e6%96%87.pdf fulltext