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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3393

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.
Other Titles: 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
Authors: Isonishi, Ayami
Bennett, Charles L.
Plaimauer, Barbara
Scheiflinger, Friedrich
Matsumoto, Masanori
Fujimura, Yoshihiro
Keywords: FFP Transfusion
Immune Thrombocytopenia
Issue Date: Oct-2015
Publisher: American Association Of Blood Banks / John Wiley & Sons, Inc.
Citation: Transfusion Vol.55 No.10 p.2321-2330 (2015 Oct)
Abstract: 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.
Description: 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
URI: http://hdl.handle.net/10564/3393
ISSN: 00411132
Academic Degrees and number: 24601B1412
Degree-granting date: 2017-11-24
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2017年度

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