Thrombosis due to dysfunction of anticoagulant activity and strategy for prevention of thrombosis

2011 Fiscal Year Final Research Report

• Project/Area Number: 20390278
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: MIYATA Toshiyuki 独立行政法人国立循環器病研究センター, 分子病態部, 部長 (90183970)
• Co-Investigator(Kenkyū-buntansha): KOKAME Koichi 独立行政法人国立循環器病研究センター, 分子病態部, 室長 (40270730) ; BANNO Fumiaki 独立行政法人国立循環器病研究センター, 分子病態部, 研究員 (00373514) ; AKIYAMA Masashi 独立行政法人国立循環器病研究センター, 分子病態部, 室長 (30298179)
• Co-Investigator(Renkei-kenkyūsha): OKADA Hiromi 国立循環器病センター病因部, 特任研究員 (00426503) ; IMOTO Hitomi 独立行政法人国立循環器病研究センター, 分子病態部, 流動研究員 (50532230) ; MATSUMOTO Sachiko 独立行政法人国立循環器病研究センター, 分子病態部, 特任研究員 (80463272) ; KITA Toshiyuki 独立行政法人国立循環器病研究センター, 分子病態部, 流動研究員 (70589986) ; SAKATA Toshiyuki 独立行政法人国立循環器病研究センター, 臨床検査部, 臨床検査技師 (80531029) ; OKAMOTO Akira 独立行政法人国立循環器病研究センター, 臨床検査部, 臨床検査技師 (10531030) ; FAN Xinping 武田科学振興財団, 派遣研究員
• Project Period (FY): 2008 – 2011
• Keywords: 静脈血栓症 / 凝固制御因子 / ADAMTS13 / 血栓性血小板減少性紫斑病 / フォンビルブランド因子 / プロテインS

Research Abstract

We have performed the genetic analysis in 173 Japanese patients with venous thromboembolism(VTE) and identified nonsynonymous mutations in 55 patients. We also performed genetic analysis in 18 pregnant women with VTE and identified the mutations in 5 patients. We estimated the frequency of hereditary deficiency of ADAMTS13. We determined the crystal structure of the ADAMTS13-DTCS domain.

Research Products

• [Journal Article] More on : racial differences in venous thromboembolism (2012)
  • Author(s): T. Miyata, N. Hamasaki, H. Wada, T. Kojima
  • Journal Title: J Thromb Haemost Volume: 10 Pages: 319-320
  • DOI: DOI:10.1111/j.1538-7836.2011.04578.x
  • Peer Reviewed
• [Journal Article] Genetic analysis of patients with deep vein thrombosis during pregnancy and postpartum (2011)
  • Author(s): R. Neki, T. Fujita, K. Kokame, I. Nakanishi, M. Waguri, Y. Imayoshi, N. Suehara, T. Ikeda, T. Miyata
  • Journal Title: Int J Hematol Volume: 94 Pages: 150-155
  • DOI: DOI:10.1007/s12185-011-0902-z
  • Peer Reviewed
• [Journal Article] Polymorphisms and mutations of ADAMTS13 in the Japanese population and estimation of the number of patients with Upshaw-Schulman syndrome (2011)
  • Author(s): K. Kokame, Y. Kokubo, T. Miyata
  • Journal Title: J Thromb Haemost Volume: 9 Pages: 1654-1656
  • DOI: DOI:10.1111/j.1538-7836.2011.04399.x
  • Peer Reviewed
• [Journal Article] von Willebrand factor-to-ADAMTS13 ratio increases with age in a Japanese population (2011)
  • Author(s): K. Kokame, T. Sakata, Y. Kokubo, T. Miyata
  • Journal Title: J Thromb Haemost Volume: 9 Pages: 1426-1428
  • DOI: DOI:10.1111-j.1538-7836.2011.04333.x
  • Peer Reviewed
• [Journal Article] Usefulness of antithrombin deficiency phenotypes for risk assessment of venous thromboembolism : type I deficiency as a strong risk factor for venous thromboembolism (2010)
  • Author(s): M. Mitsuguro, T. Sakata, A. Okamoto, S. Kameda, Y. Kokubo, Y. Tsutsumi, M. Sano, T. Miyata
  • Journal Title: Int J Hematol Volume: 92 Pages: 468-473
  • DOI: DOI:10.1007/s12185-010-0687-5
  • Peer Reviewed
• [Journal Article] The function of ADAMTS13 in thrombogenesis in vivo : insights from mutant mice (2010)
  • Author(s): F. Banno, A. K. Chauhan, T. Miyata
  • Journal Title: Int J Hematol Volume: 91 Pages: 30-35
  • DOI: DOI:10.1007/s12185-009-0477-0
  • Peer Reviewed
• [Journal Article] ADAMTS13 gene deletion aggravates ischemic brain damage : a possible neuroprotective role of ADAMTS13 by ameliorating postischemic hypoperfusion (2010)
  • Author(s): M. Fujioka, K. Hayakawa, K. Mishima, A. Kunizawa, K. Irie, S. Higuchi, T. Nakano, C. Muroi, H. Fukushima, M. Sugimoto, F. Banno, K. Kokame, T. Miyata, M. Fujiwara, K. Okuchi, K. Nishio
  • Journal Title: Blood Volume: 15 Pages: 1650-1653
  • DOI: DOI:10.1182/blood-2009-06-230110
  • Peer Reviewed
• [Journal Article] Crystal structures of the non-catalytic domains of ADAMTS13 reveal multiple discontinuous exosites for von Willebrand factor (2009)
  • Author(s): M. Akiyama, S. Takeda, K. Kokame, J. Takagi, T. Miyata
  • Journal Title: Proc Natl Acad Sci USA Volume: 106 Pages: 19274-19279
  • DOI: DOI:10.1073/pnas.0909755106
  • Peer Reviewed
• [Journal Article] Integrin-linked kinase associated with integrin activation (2009)
  • Author(s): S. Honda, H. Shirotani-Ikejima, S. Tadokoro, Y. Maeda, T. Kinoshita, Y. Tomiyama, T. Miyata
  • Journal Title: Blood Volume: 113 Pages: 5304-5313
  • DOI: DOI:10.1182/blood-2008-07-169136
  • Peer Reviewed
• [Journal Article] The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation (2009)
  • Author(s): F. Banno, AK. Chauhan, K. Kokame, J. Yang, S. Miyata, DD. Wagner, T. Miyata
  • Journal Title: Blood Volume: 113 Pages: 5323-5329
  • DOI: DOI:10.1182-blood-2008-07-169359
  • Peer Reviewed
• [Journal Article] Prevalence of genetic mutations in protein S, protein C and antithrombin genes in Japanese patients with deep vein thrombosis (2009)
  • Author(s): T. Miyata, Y. Sato, J. Ishikawa, H. Okada, S. Takeshita, T. Sakata, K. Kokame, R. Kimura, S. Honda, T. Kawasaki, E. Suehisa, H. Tsuji, S. Madoiwa, Y. Sakata, T. Kojima, M. Murata, Y. Ikeda
  • Journal Title: Thromb Res Volume: 124 Pages: 14-18
  • DOI: DOI:10.1016/j.thromres.2008.08.020
  • Peer Reviewed
• [Presentation] シンポジウム6血栓止血学・血管生物学の最近の進歩、ADAMTS13研究の最先端 (2011)
  • Author(s): 宮田敏行、小亀浩市、秋山正志、武田壮一、坂野史明
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 20111014-16
• [Presentation] 教育講演「日本人の血栓性素因」 (2010)
  • Author(s): 宮田敏行
  • Organizer: 第20回日本産婦人科・新生児血液学会
  • Place of Presentation: 浜松市
  • Year and Date: 2010-06-25
• [Presentation] 教育講演2、遺伝子情報を用いる血栓症の個別化医療 (2009)
  • Author(s): 宮田敏行
  • Organizer: 第12回日本栓子検出と治療学会
  • Place of Presentation: 大阪市
  • Year and Date: 2009-10-10
• [Presentation] The APSTH-JSTH Joint Symposium, Genetic disorders related to coagulopathy prevalent in the Far East (2009)
  • Author(s): Toshiyuki Miyata
  • Organizer: XXII Congress of the international Society on Thrombosis and Haemostasis
  • Place of Presentation: Boston, USA
  • Year and Date: 2009-07-11
• [Presentation] シンポジウム4「血栓止血・血管生物学」Thrombosis and hemostasis/vascular biology,静脈血栓塞栓症の遺伝的素因、Genetic risk factor for thrombophilia (2008)
  • Author(s): 宮田敏行
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都市
  • Year and Date: 20081010-12
• [Presentation] Binding of ADAMTS13 with Lys-plasminogen (2008)
  • Author(s): Toshiyuki MIYATA, Yongchol SHIN, Koichi KOKAME, Masashi AKIYAMA, Kenji SOEJIMA
  • Organizer: Gordon Research Conference, Hemostasis 2008
  • Place of Presentation: Waterville Valley Resort, USA
  • Year and Date: 20080629-0704
• [Book] 「VI.凝固線溶系3.内因系凝固反応と血栓症」Annual Review血液(高久史麿・小澤敬也・坂田洋一・金倉譲・小島勢二編集) (2012)
  • Author(s): 宮田敏行、喜多俊行
  • Total Pages: 236-244
  • Publisher: 中外医学社
• [Book] 「遺伝子改変血栓症モデル」疾患モデルの作製と利用-循環器疾患(北徹・堀内久徳・柳田素子・猪原匡史・冨本秀和・並河徹編集) (2010)
  • Author(s): 宮田敏行、水口純、坂野史明
  • Total Pages: 226-233
  • Publisher: 株式会社エル・アイ・シー
• [Book] Biology of an antithrombotic factor-ADAMTS13.Recent Advances in Thrombosis and Hemostasis 2008(K. Tanaka, E. W. Davie(Eds.) Y. Ikeda, S. Iwanaga, H. Saito, K. Sueishi(Associate Eds.)) (2008)
  • Author(s): F. Banno, T. Miyata
  • Total Pages: 162-176
  • Publisher: Springer