並列タイトル等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
一般注記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)
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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
DOIinfo:doi/10.1111/trf.13182
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