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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3693

Title: Disordered hemostasis associated with severely depressed fibrinolysis demonstrated using a simultaneous thrombin and plasmin generation assay during L-asparaginase induction therapy in pediatric acute lymphoblastic leukemia.
Other Titles: 小児急性リンパ性白血病のL-アスパラギナーゼを含む寛解導入療法ではトロンピン・プラスミン生成試験において著明な線溶抑制を主体とする凝固障害を示す。
Authors: Ishihara, Takashi
Nogami, Keiji
Ochi, Satoshi
Ishida, Toshiaki
Kosaka, Yoshiyuki
Sawada, Akihisa
Inoue, Masami
Osone, Shinya
Imamura, Toshihiko
Hosoi, Hajime
Shima, Midori
Keywords: acute lymphoblastic leukemia
induction therapy
L-asparaginase
thrombin and plasmin generation assay
thromboembolism
Issue Date: Jan-2020
Publisher: John Wiley
Citation: Pediatric blood and cancer Vol.67 No.1 Article No.e28016 (2019 Jan)
Abstract: Background: L-asparaginase (L-Asp)-associated thromboembolisms are serious complications in pediatrics patients with acute lymphoblastic leukemia (ALL), especially at ≥10.0 years old, but the pathogenesis remains to be clarified. Procedure: We conducted a multicenter, prospective study of 72 patients with ALL aged 1.0 to 15.2 years treated with either a Berlin-Frankfurt-Münster (BFM) 95-ALL oriented regimen or Japan Association of Childhood Leukemia Study ALL-02 protocol. We divided patients into each treatment protocol and investigated the dynamic changes in coagulation and fibrinolysis using simultaneous thrombin and plasmin generation assay. Patients' plasma samples were collected at the prephase (T0), intermittent phase (T1), and postphase of L-Asp therapy (T2), and postinduction phase (T3). Measurements of endogenous thrombin potential (T-EP) and plasmin peak height (P-Peak) were compared to normal plasma. Results: None of the cases developed thromboembolisms. Median ratios of T-EP and P-Peak for the controls in the JACLS group were 1.06 and 0.87 (T0), 1.04 and 0.71 (T1), 1.02 and 0.69 (T2), and 1.20 and 0.92 (T3), respectively, while those in the BFM group were 1.06 and 1.00 (T0), 1.04 and 0.64 (T1), 1.16 and 0.58 (T2), and 1.16 and 0.85 (T3), respectively. In particular, P-Peak ratios were depressed at T1 and T2 compared to T0 in the BFM group (P < .01). Moreover, P-Peak ratios in patients ≥10.0 years old were lower at T1 in the BFM group (P = .02). Conclusions: The results demonstrated that hemostatic dynamics appeared to shift to a hypercoagulable state with marked hypofibrinolysis associated with L-Asp therapy, especially in patients ≥10.0 years old following the BFM regimen.
Description: 博士(医学)・甲第722号・令和元年12月5日
© 2019 Wiley Periodicals, Inc.
This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1002/pbc.28016], which has been published in final form at [https://doi.org/10.1002/pbc.28016]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
URI: http://hdl.handle.net/10564/3693
ISSN: 15455009
Academic Degrees and number: 24601A722
Degree-granting date: 2019-12-05
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2019年度

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