Analysis of TMA and VOD after allogenic stem cell transplantation

2009 Fiscal Year Final Research Report

• Project/Area Number: 19591130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Nara Medical University
• Principal Investigator: MATSUMOTO Masanori Nara Medical University, 医学部, 准教授 (60316081)
• Co-Investigator(Kenkyū-buntansha): FUJIMURA Yoshihiro 奈良県立医科大学, 医学部, 教授 (80118033)
• Project Period (FY): 2007 – 2009
• Keywords: 造血幹細胞移植学

Research Abstract

Both hepatic veno-occulusive disease (VOD) and thrombotic microangiopathy (TMA) after stem cell transplantation (SCT) are life-threatening thrombotic complications. We demonstrated that prophylactic fresh frozen plasma (FFP) infusion prevented development of hepatic VOD after SCT in a multicenter, randomized trial. Forty-three patients were divided into two groups : 23 receiving FFP infusions and 20 not receiving it VOD developed only in three patients not receiving FFP. Since 1998, our laboratory has functioned as a nationwide referral center for TMA by analyzing ADAMTS13. As the end of 2008, we have established a registry of 919 patients with TMA. Of these, one-third of TMA patients had severe deficiency of ADAMTS13 activity. Fifty-four patients were classified as SCT associated TMA. None of the patients in this category had severe deficiency of ADAMTS13 activity as previously reported.

Research Products

• [Journal Article] Registry of 919 patients with thrombotic microangiopathies across Japan: Database of Nara Medical University during 1998-2008. (2010)
  • Author(s): Fujimura Y. Matsumoto M.
  • Journal Title: Inter Med 49 Pages: 7-15
• [Journal Article] Influenza A infection triggers thrombotic thrombocytopenic purpura by producing the anti-ADAMTS 13 IgG inhibitor. (2010)
  • Author(s): Kosugi N, Tsurutani Y, Isonishi A, Hon Y, Matsumoto M, Fujimura Y
  • Journal Title: Inter Med 49 Pages: 689-693
• [Journal Article] A 9-month-old infant with acquired idiopathic thrombotic thrombocytopenic purpura caused by inhibitory IgG-autoantibody to ADAMTS 13. (2010)
  • Author(s): Sato A, Hoshi Y, Onuma M, Sato R, Tsunematsu Y, Isonishi A, Matsumoto M, Fujimura Y, Imaizumi M.
  • Journal Title: Pediatr Hematol Oncol 27 Pages: 53-58
• [Journal Article] Pregnancy-induced thrombocytopenia and thrombotic microangiopathy in Upshaw-Schulman syndrome: Clinical observations and ADAMTS13 gene analysis in nine patients representing six families. (2009)
  • Author(s): Fujimura Y, Matsumoto M, Kokame K, Isonishi A, Soejima K, Akiyama N, Tomiyama J, Kazuhiko Natori K, Kuranishi Y, Imamura Y, Inoue N, Higasa S, Seike M, Kozuka T, Hara M, Wada H, Murata M, Ikeda Y, Miyata T, George JN
  • Journal Title: Br J Haematol 144 Pages: 742-754
• [Journal Article] Human Placental Ectonucleoside Triphosphate Diphosphohydrolase Gene Transfer via Gelatin-Coated Stents Prevents In-Stent Thrombosis. (2009)
  • Author(s): Takemoto Y, Kawata H, Soeda T, Imagawa K, Somekawa S, Takeda Y, Uemura S, Matsumoto M, Fujimura Y, Jo JI, Kimura Y, Tabata Y, Saito Y
  • Journal Title: Arterioscier Thromb Vase Biol 29 Pages: 857-862
• [Journal Article] The significance of ADAMTSI3 in a patient with thrombotic thrombocytopenic purpura complicated autoimmune hepatitis. (2009)
  • Author(s): Shimizu M, Nomura S, Ishii K, Mohri Y, Umei N, Suzuki S, Matsuo Y, Isonishi A, Matsumoto M, Urase F, Maeda Y, Fujimura Y
  • Journal Title: Thromb Haemost 101 Pages: 599-600
• [Journal Article] Increased production of ADAMTS13 in hepatic stellate cells contributes to enhanced plasma ADAMTS13 activity in rat models of cholestasis and steatohepatitis. (2009)
  • Author(s): Watanabe N, Ikeda H, Kume Y, Satoh Y, Kaneko M, Takai D, Tejima K, Nagamine M, Mashima H, Tomiya T, Noiri E, Omata M, Matsumoto M, Fuiimura Y, Yatomi Y
  • Journal Title: Thromb Haemost 102 Pages: 389-396
• [Journal Article] Heterogeneous pathogenic processes of thrombotic microangiopathies in patients with connective tissue diseases. (2009)
  • Author(s): Matsuyama T, Kuwana M, Matsumoto M, Isonishi A, Inokuma S, Fujimura Y
  • Journal Title: Thromb Haemost 102 Pages: 371-378
• [Journal Article] Decreased ADAMTSI3 levels in patients with living donor liver transplantation. (2009)
  • Author(s): Kobayashi T, Wada H, Usui M, Sakurai H, Matsumoto T, Nobori T, Katayama N, Uemoto S, Ishizashi H, Matsumoto M, Fujimura Y, lsaji S
  • Journal Title: Thromb Res 124 Pages: 541-545
• [Journal Article] National Questionnaire Survey of TMA. (2009)
  • Author(s): Ito N, Wada H, Matsumoto M, Fujimura Y, Murata M, Izuno 1, Sugita M, Ikeda Y
  • Journal Title: Int J Hematol 90 Pages: 328-335
• [Journal Article] Ecto-nucleotide triphosphate diphosphohydrolase inhibits ATP-and ADP-induced vasocontriction. (2008)
  • Author(s): Furukoji E, Tanaka N, Yamashita A, Matsumoto M, Fujimura Y, Yamamoto R, Tamura S, Asada Y
  • Journal Title: Thromb Res 121 Pages: 583-585
• [Journal Article] Inherited and de novo mutations of ADAMTS13 in a patient with Upahaw-Schulman syndrome. (2008)
  • Author(s): Kokame K, Aoyama Y, Matsumoto M, Fujimura Y, Miyata T
  • Journal Title: J Thromb Haemost 6 Pages: 213-215
• [Journal Article] Functional imaging of shear-dependent activity of ADAMTS 13 in regulating mural thrombis growth under whole blood flow conditions. (2008)
  • Author(s): Shida S, Nishio K, Sugimoto M, Mizuno T, Hamada M, Kato S, Matsumoto M, Okuchi K, Fujimura Y, Yoshioka A
  • Journal Title: Blood 111 Pages: 1295-1298
• [Journal Article] Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis. (2008)
  • Author(s): Uemura M, Fujimura Y, Matsumoto M, Ishizashi H, Kato S, Matsuyama T, Isonishi A, Ishikawa M, Yagita M, Morioka C, Yoshiji H, Tsujimoto T, Kurumatani N, Fukui H
  • Journal Title: Thromb Haemost 99 Pages: 1019-1029
• [Journal Article] Acute Myocardial Infarction as a Systemic Prothrombotic Condition Evidenced by Increased von Willebrand Factor Protein Over ADAMTS13 Activity in Coronary and Systemic Circulation. (2008)
  • Author(s): Horii M, Uemura S, Uemura M, Matsumoto M, Ishizashi H, Imagawa K, Iwama H, Takeda Y, Kawata H, Nakajima T, Fujimura Y, Saito Y
  • Journal Title: Heart and Vessels 23 Pages: 301-307
• [Journal Article] Plasma ADAMTS 13 activity parallels the APACHE II score, reflecting an early prognostic indicator for patients with severe acute pancreatitis. (2008)
  • Author(s): Morioka C, Uemura M, Matsuyama T, Matsumoto M, Kato S, Ishikawa M,. Ishizashi H, Fujimoto M, Sawai M, Yoshida M, Mitoro A, Yamao J, Tsujimoto T, Yoshiji H, Urizono Y, Hata M, Nishio K, Okuchi K, Fujimura Y, Fukui H
  • Journal Title: Scand J Gastroenterol 43 Pages: 1387-1396
• [Journal Article] Chemotherapy-resistant intravascular lymphoma accompanied by ADAMTS13 inhibitor successfully treated with rituximab. (2008)
  • Author(s): Kanno M, Nakamura S, Kawahara M, Ueno S, Nakamine H, Matsumoto M, Fujimura Y
  • Journal Title: Int J Hematol 88 Pages: 345-347
• [Journal Article] Increased von Willebrand factor over decreased ADAMTS 13 activity may contribute to the development of liver disturbance and multiorgan failure in patients with alcoholic hepatitis (2007)
  • Author(s): Matsuyama T, Uemura M, Ishikawa M, Matsumoto M, Ishizashi H, Kato S, Morioka C, Fujimoto M, Kojima H, Yoshiji H, Fujimura Y, Fukui H
  • Journal Title: Alcohol Clin Exp Res 31 Pages: 27S-35S
• [Journal Article] Successful Treatment of Primitive Neuroectodermal Tumor-associated Microangiopathy with Multiple Bone Metastases. (2007)
  • Author(s): Morishita T, Matsumoto M, Honoki K, Yoshida A, Takakura Y, Fujimura Y
  • Journal Title: Jap J Cli One 37 Pages: 66-69
• [Journal Article] Quantitative western blot analysis of plasma ADAMTSI3 antigen in patients with Upshaw-Schulman syndrome. (2007)
  • Author(s): Ishizashi H, Yagi H, Matsumoto M, Soejima K, Nakagaki T, Fujimura Y
  • Journal Title: Thromb Res. 120 Pages: 381-386
• [Journal Article] Decreased ADAMTS13 activity in plasma from patients with thrombotic thrombocytopenic purpura. (2007)
  • Author(s): Kobayashi T, Wada H, Kamikura Y, Matsumoto T, Mori Y, Kaneko T, Nobori T, Matsumoto M, Fujimura Y, Shiku H
  • Journal Title: Thromb Res 119 Pages: 447-452
• [Journal Article] Intravenous gamma globulin for thrombotic microangiopathy of unknown etiology. (2007)
  • Author(s): Ito S, Okuyama K, Nakamura T, Tetanishi JI, Saito K, Matsumoto M, Fujimura Y, Aihara Y, Yokota S
  • Journal Title: Pediatr Nephrol 22 Pages: 301-305
• [Journal Article] Plasma levels of ADAMTSI3 antigen, determined by an enzyme immunoassay using the neutralizing monoclonal antibody, parallel to those of the activity. (2007)
  • Author(s): Yagi H, Ito S, Kato S, Hiura H, Matsumoto M, Fujimura M
  • Journal Title: Int Hematol 85 Pages: 403-407
• [Journal Article] Two mechanistic pathways for thienopyridine-associated thrombotic thrombocytopenic purpura: A report from the Surveillance, Epidemiology, and Risk Factors for Thrombotic Thrombocytopenic Purpura (SERF-TTP) research group and the Research on Adverse Drug Events and Reports (RADAR) project. (2007)
  • Author(s): Bennett CL, Banjamin K, Zakarija A, Bandarenko N, Pandey DK, Buffie CG, McKoy JM, Tevar AD, Cursio JF, Yarnold PR, Kwaan HC, De Masi D, Sarode R, Raife TJ, Kiss JE, Raisch DW, Davidson C, Sadler JE, Ortel TL, Zheng XL, Kato S, Matsumoto M, Uemura M, Fujimura Y
  • Journal Title: J Am Coll Cardiol 50 Pages: 1138-1143
• [Journal Article] Prophylactic fresh frozen plasma infusion may prevent the development of hepatic VOD after stem cell transplantation via ADAMTS 13-mediated restoration of von Willebrand factor plasma levels. (2007)
  • Author(s): Matsumoto M, Kawa K, Uemura M, Kato S, Ishizashi H, Isonishi A, Yagi H, Park YD, Takeshima Y, Kosaka Y, Hara H, Kai S, Kanamaru A, Fukuhara S, Hino M, Sako M, Hiraoka A, Ogawa H, Ham J, Fujimura Y
  • Journal Title: Bone Marrow Transplant 40 Pages: 251-259
• [Presentation] Thrombotic thrombocytopenic purpura: Results of the patients with thrombotic micro- angiopathies across Japan by ADAMTS13 analysis during 1998-2008. (2009)
  • Author(s): Fujimura Y, Matsumoto M
  • Organizer: XXth Regional Congress of the 1SBT, Asia-Academy program (Hemostasis)
  • Place of Presentation: Nagoya
  • Year and Date: 20091100
• [Presentation] Identification of 41 Japanese patients with Upshaw-Shulman syndrome, with special reference to its genotype-phenotype analysis. (2009)
  • Author(s): Fujimura Y, Kokame K, Matsumoto M, Isonishi A, Kato S., Hiura H., Miyata T
  • Organizer: XXII ISTH congress
  • Place of Presentation: Boston
  • Year and Date: 20090700
• [Presentation] National questionnaire survey of TMA (2009)
  • Author(s): Ito N, Wada H., Sugita M, Matsumoto M, Fujimura Y, Murata M, Ikeda Y
  • Organizer: XXII ISTH congress
  • Place of Presentation: Boston
  • Year and Date: 20090700
• [Presentation] Multiple Mapping of Peptide Sequences Recognized by Various Monoclonal Anti-ADAMTS13 Antibodies with Functional or Nonfunctional Effects On the Catalytic Activity. (2009)
  • Author(s): Nakagawa T, Moriki T, Yamaguchi Y, Igari A, Soejima K, Matsumoto M, Fujimura Y, Murata M
  • Organizer: 51th ASH Annual Meeting
  • Year and Date: 20090000
• [Presentation] Characterization of Two Patient Groups with Acquired Idiopathic Thrombotic Thrombocytopenic Purpura, Defined by ADAMTS13 (n=195) and/or Classic Pentad (n=89). (2009)
  • Author(s): Matsumoto M, Isonishi A, Kato S, Ishizashi H, Yagi H, Fujimura Y
  • Organizer: 51th ASH Annual Meeting
  • Year and Date: 20090000
• [Presentation] Identification of ADAMTS13 peptide sequences recognized by autoantibodies in patients with acquired thrombotic thrombocytopenic purpura. (2008)
  • Author(s): Yusuke Yamaguchi, Takanori Moriki, Hideo Wada, Masanori Matsumoto, Yoshihiro Fujimura, Terumichi Nakagawa, Atsuko Igari, Yasuo Ikeda, Mitsuru Murata
  • Organizer: 50th ASH annual meeting
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 20080000
• [Presentation] Potential role of enhanced cytokinemia and endotoxemia on the decreased activity of plasma ADAMTS13 in patients with alcoholic hepatitis. (2008)
  • Author(s): Masatoshi Ishikawa, Masahito Uemura, Tomomi Matsuyama, Masanori Matsumoto, Masao Fujimoto, Hiromichi Ishizashi, Seiji Kato, Chie Morioka, Tatsuhiro Tsujimoto, Toshiyuki Kitazawa, Hidehito Kawaratani, Yoshihiro Fujimura, Hiroshi Fukui
  • Organizer: 50th ASH annual meeting
  • Place of Presentation: San Francisco (USA)
  • Year and Date: 20080000
• [Presentation] The ADAMTS13 analysis on thrombotic microangiopathies in Japan (2007)
  • Author(s): Matsumoto M, Fujimura Y.
  • Organizer: 6th World Congress of the International Society for Apheresis/World Apheresis Association 11th Congress
  • Place of Presentation: Yokohama (Japan)
  • Year and Date: 20070000
• [Presentation] Immuno-purification of ADAMTS13 and its physico-chemical characterization. (2007)
  • Author(s): Hiura H, Isonoshi A, Kato S, Matsumoto M, Fujimura Y
  • Organizer: XXI Congress of the ISTH
  • Place of Presentation: Geneva (Switzerland)
  • Year and Date: 20070000
• [Presentation] Alternation of von Willebrand factor and ADAMTS13 activity and its clinical significant in patients with obstructive sleep apnea syndrome. (2007)
  • Author(s): Koyama N, Makinodan K, Tamaki S, Fukuoka A, Hamada K, Matsumoto M, Fujimura Y, Kimura H
  • Organizer: XXI Congress of the ISTH
  • Place of Presentation: Geneva (Switzerland)
  • Year and Date: 20070000
• [Presentation] Analysis of ADAMTS13 in patients with collagen disease-associated TMAs. (2007)
  • Author(s): Matsuyama T, Matsumoto M, Isonishi A, Uemura M, Inokuma S, Fujimura Y
  • Organizer: XXI Congress of the ISTH
  • Place of Presentation: Geneva (Switzerland)
  • Year and Date: 20070000
• [Presentation] Analysis of ADAMTS13 and its IgG-autoantibodies in 170 patients with connective tissue disease-associated thrombotic microangiopathy indicates more than 2 types on its pathogenesis. (2007)
  • Author(s): Matsuyama T, Matsumoto M, Isonishi A, Inokuma S, Fujimura Y
  • Organizer: 49th ASH annual meeting
  • Place of Presentation: Atlanta (USA)
  • Year and Date: 20070000
• [Presentation] Clinical and outcomes findings for thrombotic thrombocytopenic purpura among 467 persons with severely versus not severely deficient ADAMTS-13 levels. (2007)
  • Author(s): Bennett CL, Luu TH, Zakarija A, Kwaan HC, Bandarenko N, Pandey DK, Curio JF, McKoy JM, Buffie C, Winters JL, Ortel TL, Sarode R, Zheng XL, Raife TJ, Matsumoto M, Fujimura Y. Rock GA
  • Organizer: 49th ASH annual meeting
  • Place of Presentation: Atlanta (USA)
  • Year and Date: 20070000
• [Presentation] Ticlopidine- and Clopidogrel- associated thrombotic thrombocytopenic purpura (TTP): final results from the serveillance epidermiology and risk factor- TTP study group. (2007)
  • Author(s): Richey EA, Bennett CL, Kwaan HC, Zakarija A, Bandarenko N, Pandey DK, Yarnold PR, Raisch DW, Winters TL, Raife TJ, Curio JF, Fisher MJ, Ortel TL, Tallman MS, Matsumoto M, Fujimura Y. Moake JL
  • Organizer: 49th ASH annual meeting
  • Place of Presentation: Atlanta (USA)
  • Year and Date: 20070000
• [Presentation] Plasma ADAMTS13 activity markedly decreased in patients with severe acute pancreatitis: Its potential role on the development of multiorgan failure. (2007)
  • Author(s): Morioka C, Uemura M, Matsuyama T, Matsumoto M, Kato S, Ishikawa M, Ishizashi H, Fujimoto M, Tsujimoto T, Nishio K, Okuchi K, Fujimura Y, Fukui H
  • Organizer: 49th ASH annual meeting
  • Place of Presentation: Atlanta (USA)
  • Year and Date: 20070000
• [Presentation] Natural history of 33 patients with Upshaw-Schulman syndrome has revealed that all the gravida develop thrombocytopenia, often followed by thrombotic microangiopathy with stillbirth. (2007)
  • Author(s): Fujimura, Y, Matsumoto M, Kokame K, Yagi H, Isonishi A, Matsuyama T, Kato S, Ishizashi H, Shida Y, Kenji N, Akiyama N, Tomiyama J, Natori K, Kuraishi Y, lmamura Y, Inoue N, Higasa S, Seike M, Kozuka T, Hara M, Sugimoto M, Wada H, Murata M, Miyata T, Ikeda Y
  • Organizer: 49th ASH annual meeting
  • Place of Presentation: Atlanta (USA)
  • Year and Date: 20070000
• [Book] 輸血療法. 小児救急アトラス(内山聖、安次嶺馨編 (2009)
  • Author(s): 松本雅則, 吉岡章
  • Total Pages: 4-6
  • Publisher: 西村書店
• [Book] 血栓性血小板減少性紫斑病疫学. 血小板減少症・増加症(池田康夫編) (2009)
  • Author(s): 松本雅則
  • Publisher: 最新医学社
• [Book] ADAMTS13とTTP-最近の進歩-. Annual Review血液2009 (2009)
  • Author(s): 松本雅則, 藤村吉博
  • Total Pages: 209-216
• [Book] Thrombotic microangiopathy. Recent Advances of Thrombosis and Hemaostasis. (2008)
  • Author(s): Fujimura Y, Matsumoto M, Yagi H
  • Total Pages: 625-639
  • Publisher: Springer Verlag
• [Book] 血栓性血小板減少性紫斑病. TODAY'STHERAPY2008今日の治療方針私はこう治療している (2008)
  • Author(s): 松本雅則
  • Total Pages: 524-526
• [Book] von Willebrand病-最近の進歩. Annual Review血液2008 (2008)
  • Author(s): 松本雅則, 藤村吉博
  • Total Pages: 211-220
• [Book] 血栓性微小血管障害症(TMA). ガイドラインパースペクティブ造血幹細胞移植(豊嶋崇徳編)
  • Author(s): 松本雅則
  • Total Pages: 116-121
  • Publisher: 医薬ジャーナル社
• [Remarks] 奈良県立医科大学輸血部ホームページ
  • URL: http://www.nararned-u.acjp/~trans/