Monitoring for anticoagulant therapy and mechanism for anticoagulant

• Project/Area Number: 24590692
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Mie University
• Principal Investigator: WADA Hideo 三重大学, 医学(系)研究科(研究院), 准教授 (40158704)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 抗Xa活性 / NOAC / 抗凝固療法 / モニター / 血栓予防

Outline of Final Research Achievements

Anti-Xa activity was negatively correlated with weight or surface area of a body. There was no significant difference in Xa activity between with and without thrombosis, but that was markedly high in the patients with major bleeding. Plasma levels of soluble fibrin (SF) and D-dimer were significantly high in the patients with thrombosis, but that was markedly high in those with major bleeding. Soluble platelet membrane glycoprotein VI (sGPVI) as a marker for platelet activation was markedly high in those with thrombosis. Disseminated intravascular coagulation (DIC) score was useful in the monitoring for DIC, and antithrombin, SF and D-dimer were useful in the monitoring for pregnant women.

Research Products

• [Journal Article] Anti-Xa activity in VTE patients treated with fonda- parinux. (2015)
  • Author(s): Ota S, Wada H, Mastuda A, Ogihara Y, Yamada N, Nakamura M, Ito M
  • Journal Title: Clin Chim Acta Volume: 442 Pages: 22-23
  • DOI: 10.1016/j.cca.2015.01.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Natural History of Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome (2014)
  • Author(s): Wada H, Matsumoto T, Yamashita Y
  • Journal Title: Semin Thromb Hemost Volume: 40 Issue: 08 Pages: 866-873
  • DOI: 10.1055/s-0034-1395154
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Elevated soluble platelet glycoprotein VI is a useful marker for DVT in postoperative patients treated with edoxaban (2014)
  • Author(s): Aota T, Naitoh K, Wada H, Yamashita Y, Miyamoto N, Hasegawa M, Wakabayashi H, Yoshida K, Asanuma K, Matsumoto T, Ohishi K, Shimokariya Y, Yamada N, Nishikawa M, Katayama N, Uchida A, Sudo A
  • Journal Title: Int J Hematol Volume: 100 Issue: 5 Pages: 450-456
  • DOI: 10.1007/s12185-014-1676-x
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Elevated plasma levels of soluble platelet glycoprotein VI (GPVI) in patients with thrombotic microangiopathy (2014)
  • Author(s): Yamashita Y, Naitoh K, Wada H, Ikejiri M, Mastumoto T, Ohishi K, Hosaka Y, Nishikawa M, Katayama N
  • Journal Title: Thromb Res Volume: 133 Pages: 440-444
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines (2014)
  • Author(s): Wada H, Matsumoto T, Yamashita Y
  • Journal Title: Journal of Intensive Care Volume: 2 Issue: 1 Pages: 15-15
  • DOI: 10.1186/2052-0492-2-15
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Behavior of ADAMTS13 and Von Willebrand factor levels in patients after living donor liver transplantation. (2013)
  • Author(s): Takahashi N, Wada H, Usui M, Kobayashi T, Habe-Ito N, Matsumoto T, Uemoto S, Nobori T, Isaji S
  • Journal Title: Thromb Res Volume: 131 Pages: 225-229
  • Peer Reviewed
• [Journal Article] Two patients with antiphospholipid antibody developed disseminated intravascular coagulation (2013)
  • Author(s): Habe K, Wada H, Ito-Habe N, Suzuki H, Nobori T, Mizutani H
  • Journal Title: Intern Med Volume: 52 Pages: 269-272
  • NAID: 130003365847
  • Peer Reviewed
• [Journal Article] Presence of antiphospholipid antibody is a risk factor in thrombotic events in patients with antiphospholipid syndrome or relevant diseases (2013)
  • Author(s): Habe K, Wada H, Matsumoto T, Ohishi K, Ikejiri M, Matsubara K, Morioka T, Kamimoto Y, Ikeda T, Katayama N, Nobori T, Mizutani H
  • Journal Title: Int J Hematol Volume: 97 Issue: 3 Pages: 345-350
  • DOI: 10.1007/s12185-013-1277-0
  • NAID: 10031162898
  • Peer Reviewed
• [Journal Article] The relationships among hemostatic markers, the withdrawal of fondaparinux due to a reduction in hemoglobin and deep vein thrombosis in Japanese patients undergoing major orthopedic surgery. (2013)
  • Author(s): Hasegawa M, Wada H, Wakabayashi H, Yoshida K, Miyamoto N, Asanuma K, Matsumoto T, Ohishi K, Shimokariya Y, Yamada N, Uchida A, Sudo A.
  • Journal Title: Clin Chim Acta Volume: 425 Pages: 109-113
  • DOI: 10.1016/j.cca.2013.07.009
  • Peer Reviewed
• [Journal Article] A prospective analysis of disseminated intravascular coagulation in patients with infections. (2013)
  • Author(s): Seki Y, Wada H, Kawasugi K, Okamoto K, Uchiyama T, Kushimoto S, Hatada T, Matsumoto T, Imai H
  • Journal Title: Intern Med Volume: 52 Pages: 1893-1898
  • NAID: 130003365784
  • Peer Reviewed
• [Journal Article] Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines (2013)
  • Author(s): Wada H, Thachil J, Di Nisio M, Mathew P, Kurosawa S, Gando S, Kim HK, Nielsen JD, Dempfle CE, Levi M, Toh CH
  • Journal Title: J Thromb Haemost Volume: 11 Issue: 4 Pages: 761-767
  • DOI: 10.1111/jth.12155
  • Peer Reviewed
• [Journal Article] Differentiating disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype from coagulopathy of trauma and acute coagulopathy of trauma-shock (COT/ACOTS) (2013)
  • Author(s): Gando S, Wada H, Tachil J
  • Journal Title: J Thromb Haemost Volume: 11 Issue: 5 Pages: 826-835
  • DOI: 10.1111/jth.12190
  • Peer Reviewed
• [Journal Article] Harmonized guidance for DIC from the ISTH and the current status of anticoagulant therapy in Japan: a rebuttal (2013)
  • Author(s): Wada H, Thachil J, Di Nisio M, Kurosawa S, Gando S, Toh CH
  • Journal Title: J Thromb Haemost Volume: 11 Issue: 11 Pages: 2078-2079
  • DOI: 10.1111/jth.12366
  • Peer Reviewed
• [Journal Article] A novel protein S gene mutation combined with protein S Tokushima mutation in a patient with superior sagittal sinus thrombosis (2012)
  • Author(s): Shindo A, Tomimoto H
  • Journal Title: J Neurol Volume: 259(1) Issue: 1 Pages: 178-179
  • DOI: 10.1007/s00415-011-6122-x
  • Peer Reviewed
• [Journal Article] Increased fibrinolysis increases bleeding in orthopedic patients receiving prophylactic fondaparinux. (2012)
  • Author(s): Yoshida K, Wada H, Hasegawa M, Wakabayashi H, Matsumoto T, Shimokariya Y, Noma K, Yamada N, Uchida A, Nobori T, Sudo A.
  • Journal Title: Int J Hematol Volume: 95 Issue: 2 Pages: 160-166
  • DOI: 10.1007/s12185-012-1004-2
  • NAID: 10030267312
  • Peer Reviewed
• [Journal Article] Frequent association of thrombophilia in cerebral venous sinus thrombosis. (2012)
  • Author(s): Ikejiri M, Shindo A, Ii Y, Tomimoto H, Yamada N, Matsumoto T, Abe Y, Nakatani K, Nobori T, Wada H
  • Journal Title: Int J Hematol Volume: 95 Issue: 3 Pages: 257-262
  • DOI: 10.1007/s12185-012-1006-0
  • NAID: 10030551794
  • Peer Reviewed
• [Journal Article] Plasma ADAMTS13, von Willebrand Factor (VWF) and VWF Propeptide Profiles in Patients with DIC and Related Diseases (2012)
  • Author(s): Habe K, Wada H, Ito-Habe N, Hatada T, Matsumoto T, Ohishi K, Maruyama K, Imai H, Mizutani H, Nobori T
  • Journal Title: Thromb Res Volume: 129 Issue: 5 Pages: 598-602
  • DOI: 10.1016/j.thromres.2011.10.011
  • Peer Reviewed
• [Journal Article] Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: A prospective multicenter survey (2012)
  • Author(s): Iba T, Saito D, Wada H, Asakura H
  • Journal Title: Thromb Res Volume: 130 Issue: 3 Pages: e129-e133
  • DOI: 10.1016/j.thromres.2012.03.021
  • Peer Reviewed
• [Journal Article] Increased Ratio of Soluble Fibrin Formation/Thrombin Generation in Patients With DIC. (2012)
  • Author(s): Kushimoto S, Wada H, Kawasugi K, Okamoto K, Uchiyama T, Seki Y, Hatada T, Imai H, Nobori T
  • Journal Title: Clin Appl Thromb Hemost Volume: 18 Issue: 6 Pages: 627-631
  • DOI: 10.1177/1076029612451648
  • Peer Reviewed
• [Journal Article] Analysis of the Cutoff Values in Fibrin-Related Markers for the Diagnosis of Overt DIC (2012)
  • Author(s): Hatada T, Wada H, Kawasugi K, Okamoto K, Uchiyama T, Kushimoto S, Seki Y, Okamura T, Imai H, Kaneko T, Nobori T
  • Journal Title: Clin Appl Thromb Hemost Volume: 18 Issue: 5 Pages: 495-500
  • DOI: 10.1177/1076029611429786
  • Peer Reviewed
• [Presentation] 播種性血管内凝固と輸血療法 (2014)
  • Author(s): 和田英夫
  • Organizer: 第21回日本輸血・細胞治療学会秋季シンポジウム
  • Place of Presentation: 愛媛（ひめぎんホール）
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] Diagnosis and therapy of DIC (2014)
  • Author(s): Wada H
  • Organizer: The 8th Congress of Asia Pacific Society on Thrombosis and haemostasis
  • Place of Presentation: Vietnam (Hanoi)
  • Year and Date: 2014-10-09 – 2014-10-11
  • Invited
• [Presentation] New guideline for DIC management (2014)
  • Author(s): Wada H
  • Organizer: The 8th Congress of Asia Pacific Society on Thrombosis and haemostasis
  • Place of Presentation: Vietnam (Hanoi)
  • Year and Date: 2014-10-09 – 2014-10-11
  • Invited
• [Presentation] 臨床検査を活用した血栓・止血異常症の診療 (2014)
  • Author(s): 和田英夫
  • Organizer: 第54回日本臨床化学会年次学術集会
  • Place of Presentation: 東京 (東京大学）
  • Year and Date: 2014-09-05 – 2014-09-07
  • Invited
• [Presentation] aHUS/TTP患者の検査値異常 (2014)
  • Author(s): 和田英夫
  • Organizer: 第49回日本小児腎臓学会シンポジウム
  • Place of Presentation: 秋田（秋田ビューホテル）
  • Year and Date: 2014-06-05 – 2014-06-07
  • Invited
• [Presentation] Guidance for diagnosis and treatment of DIC (2013)
  • Author(s): Wada H
  • Organizer: 59th SSC meeting
  • Place of Presentation: アムステルダム、オランダ
  • Invited
• [Presentation] 2013年に公表される新しいISTHのDIC診療ガイダンス (2013)
  • Author(s): 和田英夫
  • Organizer: 第35回日本血栓止血学会学術集会
  • Place of Presentation: 山形
  • Invited
• [Presentation] 救急から集中治療へ・臓器不全対策 (2013)
  • Author(s): 和田英夫
  • Organizer: 第21回日本集中治療医学会東海北陸地方会
  • Place of Presentation: 岐阜
  • Invited
• [Presentation] 旧厚生省基準などスコアリングによるDIC診断基準のエビデンス (2013)
  • Author(s): 和田英夫
  • Organizer: 第7回日本血栓止血学会学術標準化委員会シンポジウム
  • Place of Presentation: 東京
  • Invited
• [Presentation] Elevated fibrin related markers in patients with malignant diseases associated with DIC or DVT (2012)
  • Author(s): Wada H
  • Organizer: 58th SSC meeting
  • Place of Presentation: Liverpool
• [Presentation] Chairman’s report, (2012)
  • Author(s): Wada H:
  • Organizer: 58th SSC meeting
  • Place of Presentation: Liverpool
• [Presentation] 播種性血管内凝固（DIC)の病態と輸血療法 (2012)
  • Author(s): 和田英夫
  • Organizer: 第60回日本輸血・細胞治療学会
  • Place of Presentation: 福島
  • Invited
• [Presentation] 播種性血管内凝固（DIC）の病態と治療 (2012)
  • Author(s): 和田英夫
  • Organizer: 第34回日本血栓止血学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 整形外科術後の血栓予防療法に対する抗Xa活性のモニター (2012)
  • Author(s): 和田英夫
  • Organizer: 日本臨床検査自動化学会第44回大会
  • Place of Presentation: 横浜
  • Invited