Updated on 2024/04/12

写真a

 
KANEMATSU Takeshi
 
Organization
Nagoya University Hospital Department of Clinical Laboratory Assistant professor of hospital
Title
Assistant professor of hospital

Degree 2

  1. Doctor of Philosophy (Medical Science) ( 2022.3   Nagoya University ) 

  2. Bachelor of Medicine ( 2006.3   Nagoya University ) 

Research Areas 3

  1. Others / Others  / 血栓・止血学

  2. Life Science / Hematology and medical oncology

  3. Life Science / Hematology and medical oncology

Research History 1

  1. Nagoya University   Nagoya University Hospital Department of Clinical Laboratory   Assistant professor of hospital

    2018.4

Education 1

  1. Nagoya University   Faculty of Medicine

    2000.4 - 2006.3

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    Country: Japan

Professional Memberships 13

  1. 日本血栓止血学会

  2. 日本血液学会

  3. 日本内科学会

  4. 日本検査血液学会

  5. 日本輸血・細胞治療学会

  6. 日本臨床腫瘍学会

  7. International Society on Thrombosis and Haemostasis

  8. 日本輸血・細胞治療学会

  9. 日本臨床腫瘍学会

  10. 日本検査血液学会

  11. 日本血栓止血学会

  12. 日本内科学会

  13. 日本血液学会

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Papers 50

  1. Haemophilia and cardiovascular disease in Japan: Low incidence rates from ADVANCE Japan baseline data Reviewed International journal

    Nagao, A; Chikasawa, Y; Sawada, A; Kanematsu, T; Yamasaki, N; Takedani, H; Nojima, M; Fujii, T; Suzuki, N; Matsushita, T; Higasa, S; Amano, K; ADVANCE Japan Working Grp

    HAEMOPHILIA   Vol. 29 ( 6 ) page: 1519 - 1528   2023.11

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Haemophilia  

    Introduction: With the increasing life expectancy of people with haemophilia, the risk of cardiovascular disease (CVD) and thrombotic events has become a growing concern. Longitudinal studies on the incidence and risk factors of CVD in this population are limited, and optimal prevention and treatment strategies are yet to be established. Aim: This study aimed to present the baseline data of a prospective longitudinal study focusing on a subset of Japanese patients with haemophilia, specifically investigated the incidence, risk factors and treatment modalities for CVD and thrombotic diseases in people aged 40 years in Japan over 10 years through the ADVANCE Japan study. Methods: The ADVANCE Japan study is a prospective multicentre cohort study involving 600 adult individuals with haemophilia A/B aged 40 years in Japan. The primary endpoint was the incidence of CVD, with secondary endpoints encompassing anticoagulant use, mortality rates, and comparison with the general population. Results: Baseline data from the 600 participants revealed that thrombotic events occurred in 13 individuals (2.2%), mostly in those with haemophilia A. Atrial fibrillation was observed in 11 participants (1.8%). Hypertension and dyslipidaemia were identified as the prevalent risk factors. Various prophylactic treatments were employed, and no severe bleeding events were observed during the study period. Conclusion: This study provides vital baseline data for a 10-year prospective investigation of CVD and thrombotic disease risk in people with haemophilia. These findings will contribute to refining prevention and treatment approaches and improving patients’ quality of life.

    DOI: 10.1111/hae.14876

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  2. Clinical course and prognosis of patients with hepatocellular carcinoma and haemophilia Reviewed International journal

    Matsuda, N; Imai, N; Yokoyama, S; Yamamoto, K; Ito, T; Ishizu, Y; Honda, T; Okamoto, S; Kanematsu, T; Suzuki, N; Matsushita, T; Ishigami, M; Kawashima, H

    EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY   Vol. 35 ( 10 ) page: 1211 - 1215   2023.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:European Journal of Gastroenterology and Hepatology  

    Introduction Although patients with haemophilia are known to develop hepatocellular carcinoma (HCC) at a lower age than patients without, there are few reports on the clinical course and prognosis of HCC. Aim We aimed to investigate the clinical course and prognosis of patients with HCC and haemophilia. Methods Twenty-two patients with haemophilia, who were initially diagnosed with HCC between 2003 and 2021, were included. Their clinical courses and prognoses were retrospectively analysed. The results were compared with those of the 24th Nationwide Follow-up Survey of Primary Liver Cancer. Results All 22 patients were male; of these, 20 patients had haemophilia A, and 2 had haemophilia B. The mean age of diagnosis was 63 years (range 45-78 years) which is lower than the mean of 72 years reported in the Nationwide Survey. The mean diameter of the largest tumour was 30 mm (range 11-70 mm), and 18 tumours (82%) were solitary at the initial diagnosis. Standard treatments for HCC were performed in all patients. Sixty-one transarterial chemoembolisation, 28 RFA, 10 hepatectomies, and 2 radiation treatments were performed, and molecular-targeted agents were administered to 5 patients during their clinical courses. No deaths were associated with complications of HCC treatments. The median survival time after initial treatment was 6.4 years (range 0.9-18.7 years) which did not differ much from the median survival time of 5.8 years in the Nationwide Survey. Conclusion Standard treatment for HCC could improve the prognosis of patients with HCC and haemophilia.

    DOI: 10.1097/MEG.0000000000002628

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  3. The usefulness of tranexamic acid for bleeding symptoms of chronic consumptive coagulopathy complicated by aortic disease: a single-institute, retrospective study of 14 patients. Reviewed International journal

    Naruko Suzuki, Nobuaki Suzuki, Yuka Kawaguchi, Shuichi Okamoto, Takeshi Kanematsu, Akira Katsumi, Atsuo Suzuki, Shogo Tamura, Tetsuhito Kojima, Hitoshi Kiyoi, Tadashi Matsushita

    Thrombosis journal   Vol. 21 ( 1 ) page: 10 - 10   2023.1

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    BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic drug that blocks lysine-binding sites on the profibrinolytic enzyme plasminogen. Aortic diseases with chronic consumption coagulopathy may lead to disseminated intravascular coagulation (DIC) and cause fatal bleeding. Although the use of antifibrinolytic agents in DIC is generally not recommended due to enhanced fibrin deposition risking thrombotic symptoms, the efficacy of TXA has been reported in several cases of DIC with aortic diseases. However, the efficacy and safety of TXA for bleeding symptoms of chronic consumption coagulopathy with aortic diseases have not been studied in detail. METHODS: We evaluated the efficacy of TXA in 14 patients with chronic consumptive coagulopathy due to aortic disease complicated by bleeding symptoms. Changes in coagulation and fibrinolysis parameters from baseline were analyzed with Wilcoxon matched-pairs signed-rank tests, excluding missing values. Kaplan-Meier curves were used to analyze overall survival. RESULTS: Median age was 78.5 years (range, 66-89 years) and median observation period was 448 days (range, 0-2282 days). Twelve patients had chronic renal failure and 1 patient had chronic liver failure. Before starting treatment, median Japanese Ministry of Health and Welfare DIC diagnostic criteria score was 8 (range, 4-11) and median platelet count was 64 × 109/L (range, 25-97 × 109/L). Twelve patients underwent evaluation of bleeding symptoms after introduction of TXA, and 10 of those 12 patients showed improved bleeding tendencies within 30 days (median, 5.0 days). One patient with chronic liver failure showed worsening of bleeding symptoms. Although only one patient was initiated TXA in combination with anticoagulants, no significant worsening of thrombotic events was observed within 30 days. CONCLUSIONS: TXA therapy appears effective against chronic consumptive coagulopathy with bleeding due to aortic disease, with few side effects.

    DOI: 10.1186/s12959-022-00429-4

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  4. Bursitis, Bacteremia, and Disseminated Infection of <i>Mycobacteroides</i> (<i>Mycobacterium</i>) <i>abscessus</i> subsp. <i>massiliense</i> International journal

    Oka Keisuke, Morioka Hiroshi, Eguchi Motoki, Sato Yoshitaka, Tetsuka Nobuyuki, Iguchi Mitsutaka, Kanematsu Takeshi, Fukano Hanako, Hoshino Yoshihiko, Kiyoi Hitoshi, Yagi Tetsuya

    Internal Medicine   Vol. 60 ( 18 ) page: 3041 - 3045   2021

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Society of Internal Medicine  

    <p>We herein report a 59-year-old woman with a 2-year history of chronic bursitis of the hand who took 50 mg/day prednisolone for several autoimmune diseases. <i>Mycobacteroides</i> <i>abscessus</i> subsp. <i>massiliense</i> was isolated from the abscess and blood culture. Combination therapy (imipenem/cilastatin, amikacin, and clarithromycin) was administered for a month. Two months later, <i>M. massiliense</i> was detected from a blood culture again, and disseminated lesions were found. Clarithromycin and sitafloxacin were administered following eight weeks of the same regimen. Six months after the diagnosis, <i>M. massiliense</i> was isolated from a blood culture, and she expired due to multiple organ failure. </p>

    DOI: 10.2169/internalmedicine.6189-20

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  5. Lupus anticoagulant-hypoprothrombinemia syndrome associated with follicular lymphoma Reviewed International journal

    KOYAMA Daisuke, HANAJIRI Ryo, KANEMATSU Takeshi, ITO Rie, YAMAMOTO Satomi, IMOTO Naoto, SUZUKI Nobuaki, KURAHASHI Shingo, SUGIURA Isamu

    Rinsho Ketsueki   Vol. 61 ( 7 ) page: 745 - 749   2020

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Society of Hematology  

    <p>A 56-year-old woman was referred to our hospital with symptoms of swelling, purpura, and pain in her limbs. Prior to referral, bleeding in her limbs had spontaneously appeared and disappeared several times. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged, and the factor II level was 17%. The plasma-mixing test indicated lupus anticoagulant (LA), which was confirmed using aPTT-LA and dilute Russell's viper venom time (dRVVT). Therefore, she was diagnosed with lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS). During screening for underlying disorders, chest computed tomography (CT) revealed a retrosternal mass. Biopsy was not performed because the administration of freshly frozen plasma failed to correct her coagulopathy. Prednisolone (PSL) treatment (1 mg/kg) was initiated, which normalized the coagulation tests. The retrosternal mass also disappeared. PSL was tapered without LAHPS recurrence; however, the follow-up CT revealed systemic lymphadenopathy. Follicular lymphoma was diagnosed using lymph-node biopsy. Considering the subsequent LAHPS recurrence, six cycles of bendamustine + rituximab were administered. Complete response with no LAHPS recurrence was observed at the time of drafting this report. LAHPS is rare and distinct from antiphospholipid syndrome because it can cause severe bleeding. Underlying disorders should be evaluated in cases of LAHPS.</p>

    DOI: 10.11406/rinketsu.61.745

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  6. Performance Evaluation of INNOVANCE<sup>®</sup> VWF Ac Assay employing recombinant glycoprotein Ib mutant International journal

    Suzuki Atsuo, Suzuki Nobuaki, Kanematsu Takeshi, Okamoto Shuichi, Tamura Shogo, Shinohara Sho, Arai Nobuo, Kikuchi Ryosuke, Ando Yoshitaka, Kojima Tetsuhito, Matsushita Tadashi

    Japanese Journal of Thrombosis and Hemostasis   Vol. 31 ( 4 ) page: 409 - 419   2020

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Society on Thrombosis and Hemostasis  

    <p>The measurement of von Willebrand factor (VWF) activity and antigen (Ag) are required to diagnose von Willebrand disease (VWD). In Japan, ristocetin cofactor activity of VWF (VWF:RCo) has been used in a clinical setting. INNOVANCE<sup>®</sup> VWF Ac Assay is based on latex immunoagglutination and measures VWF:GPIbM activity, which employ recombinant glycoprotein Ib carrying two gain-of-function mutation. However, it has not been introduced in Japan yet. Here, we evaluated the performance of INNOVANCE<sup>®</sup> VWF Ac Assay in CS-5100 autoanalyzer. The results showed that within-run and between-day precision were the CVs of <3% and <2%, respectively. We observed a good dilution linearity and a superior limit of detection compared with VWF:RCo. The VWF:GPIbM assay was not affected by interference substances such as bilirubin, hemolytic hemoglobin and chyle, and also by unfractionated heparin (<10 IU/mL). The correlations of VWF:GPIbM versus VWF:RCo or VWF:Ag were excellent in normal plasma. In plasma from patients with VWD, VWF:GPIbM activity was also correlated with VWF:RCo. Taken together, INNOVANCE<sup>®</sup> VWF Ac Assay showed a remarkable performance and it would be expected the future introduction in Japan.</p>

    DOI: 10.2491/jjsth.31.409

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  7. Ischemic events are rare among aging patients with hemophilia: Results of a cross-sectional study from at centers treating hemophiliacs in Japan Reviewed International journal

    Suzuki Nobuaki, Takedani Hideyuki, Yamasaki Naoya, Chikasawa Yushi, Sawada Akihiro, Kanematsu Takeshi, Higasa Satoshi, Amano Kagehiro, Fukutake Katsuyuki, Nagao Azusa

    HAEMOPHILIA   Vol. 24   page: 13 - 14   2018.5

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  8. 病気のはなし ハイド症候群 Reviewed International journal

    兼松 毅, 松下 正

    検査と技術   Vol. 42 ( 11 ) page: 1188 - 1192   2014.10

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:株式会社医学書院  

    DOI: 10.11477/mf.1543104485

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  9. Basement membrane extract potentiates the endochondral ossification phenotype of bone marrow-derived mesenchymal stem cell-based cartilage organoids. Reviewed International journal

    Hinako Notoh, Satoshi Yamasaki, Nobuaki Suzuki, Atsuo Suzuki, Shuichi Okamoto, Takeshi Kanematsu, Naruko Suzuki, Akira Katsumi, Tetsuhito Kojima, Tadashi Matsushita, Shogo Tamura

    Biochemical and biophysical research communications   Vol. 701   page: 149583 - 149583   2024.3

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    Endochondral ossification is a developmental process in the skeletal system and bone marrow of vertebrates. During endochondral ossification, primitive cartilaginous anlages derived from mesenchymal stem cells (MSCs) undergo vascular invasion and ossification. In vitro regeneration of endochondral ossification is beneficial for research on the skeletal system and bone marrow development as well as their clinical aspects. However, to achieve the regeneration of endochondral ossification, a stem cell-based artificial cartilage (cartilage organoid, Cart-Org) that possesses an endochondral ossification phenotype is required. Here, we modified a conventional 3D culture method to create stem cell-based Cart-Org by mixing it with a basement membrane extract (BME) and further characterized its chondrogenic and ossification properties. BME enlarged and matured the bone marrow MSC-based Cart-Orgs without any shape abnormalities. Histological analysis using Alcian blue staining showed that the production of cartilaginous extracellular matrices was enhanced in Cart-Org treated with BME. Transcriptome analysis using RNA sequencing revealed that BME altered the gene expression pattern of Cart-Org to a dominant chondrogenic state. BME triggered the activation of the SMAD pathway and inhibition of the NK-κB pathway, which resulted in the upregulation of SOX9, COL2A1, and ACAN in Cart-Org. BME also facilitated the upregulation of genes associated with hypertrophic chondrocytes (IHH, PTH1R, and COL10A1) and ossification (SP7, ALPL, and MMP13). Our findings indicate that BME promotes cartilaginous maturation and further ossification of bone marrow MSC-based Cart-Org, suggesting that Cart-Org treated with BME possesses the phenotype of endochondral ossification.

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  10. Variability in combinations of APTT reagent and substrate plasma for a one-stage clotting assay to measure factor VIII products. Reviewed International journal

    Atsuo Suzuki, Nobuaki Suzuki, Takeshi Kanematsu, Shuichi Okamoto, Naruko Suzuki, Shogo Tamura, Ryosuke Kikuchi, Akira Katsumi, Tetsuhito Kojima, Tadashi Matsushita

    International journal of laboratory hematology     2024.3

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    INTRODUCTION: An investigation of the suitability of reagents for measuring FVIII products in a one-stage clotting assay (OSA) showed variations in their FVIII activity (FVIII:C). Most studies have focused on the activated partial thromboplastin time (APTT) reagent rather than FVIII-deficient plasma (F8DP), even though the APTT-based OSA is comprised of APTT reagents and factor-deficient plasma. AIM: A single-centre study was conducted to clarify variations in measurements of FVIII products in an OSA using a total of 12 reagent combinations, including four APTT reagents and three types of F8DP. METHODS: FVIII:C in nine types of FVIII product-spiked plasma was measured using an OSA with four different APTT reagents and three types of F8DP. RESULTS: F8DP-dependent variations were found in addition to differences derived from APTT reagents. Variations in target recovery (TR) were observed for NovoEight®, Eloctate®, and Jivi®. Reduced TR for Jivi was found only for Pathromtin SL in combination with congenital F8DP (F8DP-3). This lower TR was not observed with alternative manufacturing lots of F8DP-3. The reduced TR for Jivi might be related to impaired contact activation due to lower factor XI activity in F8DP-3. CONCLUSION: In addition to APTT reagents, variations in F8DPs used for OSAs can also affect FVIII:C results. F8DPs as well as the APTT reagent used for OSA should be chosen with caution, and laboratories should evaluate reagents for F8DPs as they currently do for APTT reagents, especially when lot changes occur.

    DOI: 10.1111/ijlh.14258

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  11. VWF-Gly2752Ser, a novel non-cysteine substitution variant in the CK domain, exhibits severe secretory impairment by hampering C-terminal dimer formation. Reviewed International journal

    Shuichi Okamoto, Shogo Tamura, Naomi Sanda, Koya Odaira, Yuri Hayakawa, Masato Mukaide, Atsuo Suzuki, Takeshi Kanematsu, Fumihiko Hayakawa, Akira Katsumi, Hitoshi Kiyoi, Tetsuhito Kojima, Tadashi Matsushita, Nobuaki Suzuki

    Journal of thrombosis and haemostasis : JTH   Vol. 20 ( 8 ) page: 1784 - 1796   2022.8

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    BACKGROUND: Von Willebrand factor (VWF) is a multimeric glycoprotein that plays important roles in hemostasis and thrombosis. C-terminal interchain-disulfide bonds in the cystine knot (CK) domain are essential for VWF dimerization. Previous studies have reported that missense variants of cysteine in the CK domain disrupt the intrachain-disulfide bond and cause type 3 von Willebrand disease (VWD). However, type 3 VWD-associated noncysteine substitution variants in the CK domain have not been reported. OBJECTIVE: To investigate the molecular mechanism of a novel non-cysteine variant in the CK domain, VWF c.8254 G>A (p.Gly2752Ser), which was identified in a patient with type 3 VWD as homozygous. METHODS: Genetic analysis was performed by whole exome sequencing and Sanger sequencing. VWF multimer analysis was performed using SDS-agarose electrophoresis. VWF production and subcellular localization were analyzed using ex vivo endothelial colony forming cells (ECFCs) and an in vitro recombinant VWF (rVWF) expression system. RESULTS: The patient was homozygous for VWF-Gly2752Ser. Plasma VWF enzyme-linked immunosorbent assay showed that the VWF antigen level of the patient was 1.2% compared with healthy subjects. A tiny amount of VWF was identified in the patient's ECFC. Multimer analysis revealed that the circulating VWF-Gly2752Ser presented only low molecular weight multimers. Subcellular localization analysis of VWF-Gly2752Ser-transfected cell lines showed that rVWF-Gly2752Ser was severely impaired in its ER-to-Golgi trafficking. CONCLUSION: VWF-Gly2752Ser causes severe secretory impairment because of its dimerization failure. This is the first report of a VWF variant with a noncysteine substitution in the CK domain that causes type 3 VWD.

    DOI: 10.1111/jth.15746

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  12. EFFICACY OF DESENSITIZATION THERAPY FOR ALLERGY TO FACTOR IX CONCENTRATES Reviewed International journal

    Nobuaki Suzuki, Takeshi Kanematsu, Mayuko Kishimoto, Naruko Suzuki, Shuichi Okamoto, Shogo Tamura, Hitoshi Kiyoi, Tadashi Matsushita

    Japanese Journal of Transfusion and Cell Therapy   Vol. 68 ( 3 ) page: 422 - 427   2022.6

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Japan Society of Transfusion Medicine and Cell Therapy  

    <p>We report two cases of hemophilia B with severe allergy to factor IX concentrates who responded well to desensitization therapy (DT). Case 1 is a 9-month-old boy with severe hemophilia B who developed anaphylaxis on the 10th exposure day (ED) to recombinant factor IX (rFIX) after starting primary prophylaxis. Case 2 is a 55-year-old male with moderate hemophilia B. He received on-demand plasma-derived FIX (pdFIX) for bleeding symptoms and developed anaphylaxis after the 4th ED to pdFIX. DT with rFIX was performed for case 1 and 2. Results: FIX allergy symptoms disappeared in both cases after DT. No adverse events were observed during DT, including allergic symptoms. Discussion: Case 2 developed anaphylaxis despite his disease severity being moderate and risk of allergy considered low. Both patients were suspected of having low inhibitor levels before and after the onset of anaphylaxis, suggesting that attention to the onset of inhibitors may be predictive of anaphylaxis. The treatment protocol for DT remains to be optimized and requires further investigation.</p>

    DOI: 10.3925/jjtc.68.422

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  13. F9 mRNA splicing aberration due to a deep Intronic structural variation in a patient with moderate hemophilia B. Reviewed International journal

    Koya Odaira, Fumika Kawashima, Shogo Tamura, Nobuaki Suzuki, Mahiru Tokoro, Yuri Hayakawa, Atsuo Suzuki, Takeshi Kanematsu, Shuichi Okamoto, Akira Takagi, Akira Katsumi, Tadashi Matsushita, Midori Shima, Keiji Nogami, Tetsuhito Kojima, Fumihiko Hayakawa

    Thrombosis research   Vol. 213   page: 91 - 96   2022.5

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    INTRODUCTION: Hemophilia B (HB) is a hereditary bleeding disorder caused by the genetic variation of the coagulation factor IX (FIX) gene (F9). Several F9 structural abnormalities, including large deletion and/or insertion, have been observed to cause HB development. However, there is limited information available on F9 deep intronic variations. In this study, we report about a novel large deletion/insertion observed in a deep region of F9 intron 1 that causes mRNA splicing abnormalities. PATIENT AND METHODS: The patient was a Japanese male diagnosed with moderate HB (FIX:C = 3.0 IU/dL). The genomic DNA of the patient was isolated from peripheral blood leukocytes. DNA sequences of F9 exons and splice donor/acceptor sites were analyzed via polymerase chain reaction and Sanger sequencing. Variant-affected F9 mRNA aberration and FIX protein production, secretion, and coagulant activity were analyzed by cell-based exon trap and splicing-competent FIX expression vector systems. RESULTS: A 28-bp deletion/476-bp insertion was identified in the F9 intron 1 of a patient with moderate HB. A DNA sequence identical to a part of the inverted HNRNPA1 exon 12 was inserted. Cell-based transcript analysis revealed that this large intronic deletion/insertion disrupted F9 mRNA splicing pattern, resulting in reduction of protein-coding F9 mRNA. CONCLUSION: A novel deep intronic F9 rearrangement was identified in a Japanese patient with moderate HB. Abnormal F9 mRNA splicing pattern due to this deep intronic structural variation resulted in a reduction of protein-coding F9 mRNA, which probably caused the moderate HB phenotype.

    DOI: 10.1016/j.thromres.2022.03.010

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  14. Periosteum-derived podoplanin-expressing stromal cells regulate nascent vascularization during epiphyseal marrow development. Reviewed International journal

    Shogo Tamura, Masato Mukaide, Yumi Katsuragi, Wataru Fujii, Koya Odaira, Nobuaki Suzuki, Nagaharu Tsukiji, Shuichi Okamoto, Atsuo Suzuki, Takeshi Kanematsu, Akira Katsumi, Akira Takagi, Katsuhide Ikeda, Jun Ueyama, Masaaki Hirayama, Katsue Suzuki-Inoue, Tadashi Matsushita, Tetsuhito Kojima, Fumihiko Hayakawa

    The Journal of biological chemistry   Vol. 298 ( 5 ) page: 101833 - 101833   2022.5

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    Bone marrow development and endochondral bone formation occur simultaneously. During endochondral ossification, periosteal vasculatures and stromal progenitors invade the primary avascular cartilaginous anlage, which induces primitive marrow development. We previously determined that bone marrow podoplanin (PDPN)-expressing stromal cells exist in the perivascular microenvironment and promote megakaryopoiesis and erythropoiesis. In this study, we aimed to examine the involvement of PDPN-expressing stromal cells in postnatal bone marrow generation. Using histological analysis, we observed that periosteum-derived PDPN-expressing stromal cells infiltrated the cartilaginous anlage of the postnatal epiphysis and populated on the primitive vasculature of secondary ossification center. Furthermore, immunophenotyping and cellular characteristic analyses indicated that the PDPN-expressing stromal cells constituted a subpopulation of the skeletal stem cell lineage. In vitro xenovascular model cocultured with human umbilical vein endothelial cells and PDPN-expressing skeletal stem cell progenies showed that PDPN-expressing stromal cells maintained vascular integrity via the release of angiogenic factors and vascular basement membrane-related extracellular matrices. We show that in this process, Notch signal activation committed the PDPN-expressing stromal cells into a dominant state with basement membrane-related extracellular matrices, especially type IV collagens. Our findings suggest that the PDPN-expressing stromal cells regulate the integrity of the primitive vasculatures in the epiphyseal nascent marrow. To the best of our knowledge, this is the first study to comprehensively examine how PDPN-expressing stromal cells contribute to marrow development and homeostasis.

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  15. Protein S-Leu17Pro disrupts the hydrophobicity of its signal peptide causing a proteasome-dependent degradation. Reviewed International journal

    Kentaro Okada, Shogo Tamura, Nobuaki Suzuki, Koya Odaira, Masato Mukaide, Wataru Fujii, Yumi Katsuragi, Atsuo Suzuki, Takeshi Kanematsu, Shuichi Okamoto, Naruko Suzuki, Akira Katsumi, Tadashi Matsushita, Tetsuhito Kojima, Fumihiko Hayakawa

    Thrombosis research   Vol. 210   page: 26 - 32   2022.2

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    INTRODUCTION: Protein S is a vitamin K-dependent glycoprotein with important anticoagulant, fibrinolytic, anti-inflammatory, anti-apoptotic, and cytoprotective functions. Congenital protein S deficiency is an autosomal dominant thrombophilia due to protein S gene (PROS1) variations. Our group identified a variation in PROS1 that translates into protein S deficiency: c.50 T > C (p.Leu17Pro). Here, we investigated the mechanisms by which this variation results in protein S deficiency. MATERIALS AND METHODS: The effect of L17P substitution on protein S signal peptide was predicted by in silico (a computational prediction technique) analysis of hydrophobicity and signal peptide cleavage. Recombinant protein S was overexpressed in HEK293 and COS-7 cells. Intracellular kinetics and extracellular secretion of recombinant protein S-L17P were analyzed by western blotting and immunocytochemistry. RESULTS: In silico hydrophobicity analysis showed that protein S-L17P had disrupted hydrophobic status in the h-region of its signal peptide. Under normal culture conditions, recombinant protein S -L17P was not detected in either transfectant cell lysates or medium. Upon treatment with a proteasome inhibitor, recombinant protein S-L17P was clearly detected in the cell lysate, but not in the culture medium. Recombinant protein S-L17P did not undergo post-translational modification with N-glycosylation, suggesting that the nascent polypeptide of recombinant protein S-L17P is not transported to the endoplasmic reticulum lumen, but is mislocalized to the cytosol. CONCLUSION: PROS1-L17P variation translates into protein S deficiency. Protein S-L17P causes its cytosolic mislocalization resulting in its proteasome-dependent degradation.

    DOI: 10.1016/j.thromres.2021.12.014

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  16. Development and validation of a novel qualitative test for plasma fibrinogen utilizing clot waveform analysis. Reviewed International journal

    Suzuki A, Suzuki N, Kanematsu T, Shinohara S, Kurono H, Arai N, Okamoto S, Suzuki N, Tamura S, Kikuchi R, Katsumi A, Kojima T, Matsushita T

    Scientific Reports   Vol. 12 ( 1 ) page: 434   2022.1

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    <title>Abstract</title>Plasma fibrinogen is commonly examined by Clauss fibrinogen assay, which cannot distinguish between quantitative and qualitative fibrinogen anomalies. However, our previously reported Clauss fibrinogen assay utilizing clot waveform analysis (Clauss-CWA) provides additional information that contributes to the classification of fibrinogen anomalies. In this study, we adopted the Clauss-CWA method for an autoanalyzer to automatically measure the antigenic estimate (eAg) of fibrinogen in addition to the functional amount (Ac), and to thus provide the Ac/eAg ratio as a qualitative indicator. Performance was validated by receiver operating characteristics (ROC) and precision recall (PR) curve analyses using a patient cohort, consisting of a training cohort (n = 519) and a validation cohort (n = 523), both of which contained cases of congenital (hypo)dysfibrinogenemia as qualitative defects. We obtained an optimal cutoff of 0.65 for Ac/eAg by ROC curve analysis of the training cohort, offering superior sensitivity (&gt; 0.9661) and specificity (1.000). This cutoff was validated in the validation cohort, providing positive predictive value &gt; 0.933 and negative predictive value &gt; 0.998. PR curve analysis also showed that Clauss-CWA provided excellent performance for detecting qualitative fibrinogen anomalies. The Clauss-CWA method may represent a useful approach for detecting qualitative fibrinogen abnormalities in routine laboratory testing.

    DOI: 10.1038/s41598-021-04464-5

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    Other Link: https://www.nature.com/articles/s41598-021-04464-5

  17. The influence of hepatitis C virus eradication on hepatocarcinogenesis in patients with hemophilia. Reviewed International journal

    Yosuke Inukai, Norihiro Imai, Kenta Yamamoto, Takanori Ito, Yoji Ishizu, Takashi Honda, Shuichi Okamoto, Takeshi Kanematsu, Nobuaki Suzuki, Tadashi Matsushita, Masatoshi Ishigami, Mitsuhiro Fujishiro

    Annals of hepatology   Vol. 27 ( 1 ) page: 100545 - 100545   2022.1

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    INTRODUCTION AND OBJECTIVES: Hepatitis C virus (HCV) infections in patients with hemophilia lead to the development of hepatocellular carcinoma (HCC) at a relatively younger age than that in patients without hemophilia. Although recent progress in direct-acting-antivirals has facilitated a high rate of sustained virological response (SVR), the clinical influence of HCV eradication in hemophilia patients remains unclear. This study aimed to compare the clinical outcomes of SVR against HCV in patients with and without hemophilia. PATIENTS AND METHODS: The study enrolled 699 patients who achieved SVR after HCV antiviral treatment. Patients were divided into two groups: 78 patients with hemophilia (H group) and 621 patients without hemophilia (NH group). We evaluated patient characteristics, clinical outcomes, and the cumulative incidence of HCC after SVR. RESULTS: Compared with the NH group, patients in the H-group were significantly younger and had a lower hepatic fibrosis score. No difference was found in the incidence of liver-related disease or overall death between the two groups over a mean follow-up period of 7 years. Four patients in the H group and 36 patients in the NH group were diagnosed with HCC after SVR. Multivariate analysis showed that male sex, age, and cirrhosis were significant risk factors for HCC incidence. There was no significant difference in the cumulative incidence of HCC after propensity-score matching adjusting for the risk factors of HCC between the two groups. CONCLUSION: Hemophilia is not a significant risk factor for hepatocarcinogenesis after SVR against HCV.

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  18. Tolerability of Molecular-targeted Agents for Hepatocellular Carcinoma Treatment in Haemophiliacs. Reviewed International journal

    Takafumi Yamamoto, Norihiro Imai, Kenta Yamamoto, Takanori Ito, Yoji Ishizu, Takashi Honda, Shuichi Okamoto, Takeshi Kanematsu, Nobuaki Suzuki, Tadashi Matsushita, Masatoshi Ishigami, Mitsuhiro Fujishiro

    Anticancer research   Vol. 41 ( 5 ) page: 2569 - 2573   2021.5

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    BACKGROUND: Hepatocellular carcinoma (HCC) is considered a leading cause of death in patients with haemophilia. Recent advances in the treatment of unresectable HCC with molecular-targeted agents (MTAs) have led to better clinical outcomes. However, the tolerability of MTAs by haemophilic patients with HCC remains unclear. AIM: This study aimed to compare the tolerability of MTAs in such patients. PATIENTS AND METHODS: From January 2011 to October 2020, five haemophilic patients with HCC were treated with MTAs. Adverse events were assessed in comparison with 265 non-haemophilic patients with HCC. RESULTS: The prevalence of hand-foot skin reaction was not higher in the haemophiliacs than in the non-haemophiliacs, whereas the rate of haemorrhagic events was higher in the haemophiliacs (6.0% versus 40.0%, p=0.037). CONCLUSION: Haemophiliacs tolerate long-term MTA use, without the occurrence of life-threatening complications. However, careful observation and prevention are needed for MTA-related gastrointestinal bleeding in haemophiliacs.

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  19. 第VIII因子製剤の活性測定における試薬バリエーションを把握するための単施設研究 Reviewed International journal

    鈴木 敦夫, 鈴木 伸明, 兼松 毅, 岡本 修一, 田村 彰吾, 小嶋 哲人, 松下 正

    日本血栓止血学会誌   Vol. 32 ( 2 ) page: 198 - 198   2021.5

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  20. Essential role of a carboxyl-terminal α-helix motif in the secretion of coagulation factor XI. Reviewed International journal

    Yuri Hayakawa, Shogo Tamura, Nobuaki Suzuki, Koya Odaira, Mahiru Tokoro, Fumika Kawashima, Fumihiko Hayakawa, Akira Takagi, Akira Katsumi, Atsuo Suzuki, Shuichi Okamoto, Takeshi Kanematsu, Tadashi Matsushita, Tetsuhito Kojima

    Journal of thrombosis and haemostasis : JTH   Vol. 19 ( 4 ) page: 920 - 930   2021.4

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    BACKGROUND: Coagulation factor XI (FXI) is a plasma serine protease zymogen that contributes to hemostasis. However, the mechanism of its secretion remains unclear. OBJECTIVE: To determine the molecular mechanism of FXI secretion by characterizing a novel FXI mutant identified in a FXI-deficient Japanese patient. PATIENT/METHODS: The FXI gene (F11) was analyzed by direct sequencing. Mutant recombinant FXI (rFXI) was overexpressed in HEK293 or COS-7 cells. Western blotting and enzyme-linked immunosorbent assay were performed to examine the FXI extracellular secretion profile. Immunofluorescence microscopy was used to investigate the subcellular localization of the rFXI mutant. RESULTS: We identified a novel homozygous frameshift mutation in F11 [c.1788dupC (p.E597Rfs*65)], resulting in a unique and extended carboxyl-terminal (C-terminal) structure in FXI. Although rFXI-E597Rfs*65 was intracellularly synthesized, its extracellular secretion was markedly reduced. Subcellular localization analysis revealed that rFXI-E597Rfs*65 was abnormally retained in the endoplasmic reticulum (ER). We generated a series of C-terminal-truncated rFXI mutants to further investigate the role of the C-terminal region in FXI secretion. Serial rFXI experiments revealed that a threonine at position 622, the fourth residue from the C-terminus, was essential for secretion. Notably, Thr622 engages in the formation of an α-helix motif, indicating the importance of the C-terminal α-helix in FXI intracellular behavior and secretion. CONCLUSION: FXI E597Rfs*65 results in the pathogenesis of a severe secretory defect resulting from aberrant ER-to-Golgi trafficking caused by the lack of a C-terminal α-helix motif. This study demonstrates the impact of the C-terminal structure, especially the α-helix motif, on FXI secretion.

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  21. Impact of variation in reagent combinations for one-stage clotting assay on assay discrepancy in nonsevere haemophilia A. Reviewed International journal

    Atsuo Suzuki, Nobuaki Suzuki, Takeshi Kanematsu, Shuichi Okamoto, Shogo Tamura, Ryosuke Kikuchi, Akira Katsumi, Hitoshi Kiyoi, Tetsuhito Kojima, Tadashi Matsushita

    International journal of laboratory hematology   Vol. 43 ( 1 ) page: 131 - 138   2021.2

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    INTRODUCTION: Factor VIII activity (FVIII:C) is measured by one-stage clotting assay (OSA) or chromogenic substrate assay (CSA). Significant differences in FVIII:C between OSA (FVIII:C1st ) and CSA (FVIII:CChr ) are described as assay discrepancy in nonsevere haemophilia A (HA). A large number of reagent combinations (APTT reagent and FVIII-deficient plasma) are used for OSA, but the impact of variations in reagent combinations on assay discrepancy has not been fully characterized. AIM: To clarify the variations in FVIII:C1st /FVIII:CChr ratios according to OSA reagent combination in HA subjects with/without assay discrepancy. METHODS: Thirty-nine patients previously diagnosed with nonsevere HA were enrolled, and their FVIII genes were investigated and FVIII:C levels were assessed by a single CSA reagent and 11 OSA reagent combinations. Receiver operating characteristic (ROC) curve analysis was used to predict possible cut-off values of the FVIII:C1st /FVIII:CChr ratio to define FVIII assay discrepancy for each reagent combination. RESULTS: Patients were categorized into nondiscrepant (n = 25), discrepant (n = 5) and unclassified (n = 9) groups according to their genotypes and information in the database. The FVIII:C1st /FVIII:CChr ratio in nondiscrepant HA varied widely, depending on the APTT reagents and FVIII-deficient plasma used. The ratio in discrepant HA patients differed with respect to their genotype and the reagent combination used. ROC curve analyses revealed that cut-off values to distinguish the assay discrepancy differed depending on the reagents used, but revealed two novel genotype variants, p.Cys573Gly and p.Gly582Arg, associated with FVIII assay discrepancy. CONCLUSION: Our findings showed that the FVIII:C1st /FVIII:CChr ratio is dependent on the reagent combination used for OSA.

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  22. Myh9 R702C is associated with erythroid abnormality with splenomegaly in mice. Reviewed

    Takeshi Kanematsu, Nobuaki Suzuki, Shogo Tamura, Atsuo Suzuki, Yuichi Ishikawa, Akira Katsumi, Hitoshi Kiyoi, Hidehiko Saito, Shinji Kunishima, Tetsuhito Kojima, Tadashi Matsushita

    Nagoya journal of medical science   Vol. 83 ( 1 ) page: 75 - 86   2021.2

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    MYH9 disorders are characterized by giant platelets, thrombocytopenia, and Döhle body-like cytoplasmic inclusion bodies in granulocytes. However, whether these disorders cause any changes in erythroid cells has yet to be determined. This study analyzed the influence of Myh9 R702C, as one of the most commonly detected MYH9 disorders, on erythroid cells in a mouse model. Knock-in mice expressing Myh9 R702C mutation either systemically or specific to hematological cells (R702C and R702C vav1 mice, respectively) were used in this study. Both displayed lower hemoglobin and higher erythropoietin levels than wild-type (WT) mice, along with significant splenomegaly. Flow cytometric analysis revealed erythroblasts present at a higher rate than WT mice in the spleen. However, no obvious abnormalities were seen in erythroid differentiation from megakaryocyte/erythroid progenitor to erythrocyte. Cell culture assay by fetal liver and colony assay also showed normal progression of erythroid differentiation from erythroid burst-forming unit to red blood cell. In conclusion, R702C and R702C vav1 mice displayed erythroid abnormality with splenomegaly. However, erythroid differentiation showed no obvious abnormality. Further research is required to elucidate the underlying mechanisms.

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  23. Safety and efficacy of percutaneous radiofrequency ablation for hepatocellular carcinoma patients with haemophilia. Reviewed International journal

    Takafumi Yamamoto, Norihiro Imai, Kenta Yamamoto, Takanori Ito, Yoji Ishizu, Takashi Honda, Shuichi Okamoto, Takeshi Kanematsu, Nobuaki Suzuki, Tadashi Matsushita, Masatoshi Ishigami, Mitsuhiro Fujishiro

    Haemophilia : the official journal of the World Federation of Hemophilia   Vol. 27 ( 1 ) page: 100 - 107   2021.1

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    UNLABELLED: Haemophilia is an X-linked inherited bleeding disorder caused by coagulation factor deficiency. Hepatocellular carcinoma (HCC) is a major complication associated with the disease. No study thus far has investigated the safety and efficacy of percutaneous radiofrequency ablation (RFA) for HCC in patients with haemophilia. AIM: This study aimed to evaluate the safety and efficacy of RFA for HCC in haemophilia patients. METHODS: From July 2008 to June 2019, 217 patients with HCC underwent 300 RFA sessions. Of these, 18 sessions were performed in ten haemophilia patients (H group) and 282 in 207 non-haemophilia patients (NH group). The patients' characteristics, incidence of haemorrhagic complications and rates of local tumour recurrence were compared between the groups. RESULTS: A majority of the haemophilia patients received clotting factor concentrate replacement therapy before and after RFA treatment, with the aim of reaching a plasma clotting factor level of higher than 60%-80%. Twelve haemorrhagic complications were observed in the NH group (4.2%; 12/282). Major bleeding requiring control procedures was observed in two patients and minor bleeding with careful observation was noted in ten patients. No bleeding complications were observed in the H group (0/18). There were no significant differences in the 5-year local tumour recurrence rates after RFA treatment between the groups (35.0% in the H group and 32.1% in the NH group). CONCLUSION: RFA could be an effective and a safe method for HCC treatment in patients with haemophilia.

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  24. Aberrant X chromosomal rearrangement through multi-step template switching during sister chromatid formation in a patient with severe hemophilia A. Reviewed International journal

    Mahiru Tokoro, Shogo Tamura, Nobuaki Suzuki, Misaki Kakihara, Yuna Hattori, Koya Odaira, Sachiko Suzuki, Akira Takagi, Akira Katsumi, Fumihiko Hayakawa, Shuichi Okamoto, Atsuo Suzuki, Takeshi Kanematsu, Tadashi Matsushita, Tetsuhito Kojima

    Molecular genetics & genomic medicine   Vol. 8 ( 9 ) page: e1390   2020.9

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    BACKGROUND: Hemophilia A (HA) is an X-linked recessive bleeding disorder caused by pathogenic variants of the coagulation factor VIII gene (F8). Half of the patients with severe HA have a recurrent inversion in the X chromosome, that is, F8 intron 22 or intron 1 inversion. Here, we characterized an abnormal F8 due to atypical complex X chromosome rearrangements in a Japanese patient with severe HA. METHODS: Recurrent F8 inversions were tested with inverse shifting-PCR. The genomic structure was investigated using PCR-based direct sequencing or quantitative PCR. RESULTS: The proband's X chromosome had a 119.5 kb insertion, a reverse duplex of an extragenic sequence on the F8 telomere region into the F8 intron 1 with two breakpoints. The telomeric breakpoint was a joining from the F8 intron 1 to the inverted FUNDC2 via a two-base microhomology, and the centromeric breakpoint was a recombination between F8 intron 1 homologous sequences. The rearrangement mechanism was suggested as a multi-step rearrangement with template switching such as fork stalling and template switching (FoSTeS)/microhomology-mediated break-induced replication (MMBIR) and/or homologous sequence-associated recombination during a sister chromatid formation. CONCLUSION: We identified the aberrant X chromosome with a split F8 due to a multi-step rearrangement in a patient with severe HA.

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  25. 血小板膜糖蛋白質GPIb変異体を用いたvon Willebrand因子活性測定試薬「INNOVANCE VWF Ac」の基本性能評価 Reviewed International journal

    鈴木 敦夫, 鈴木 伸明, 兼松 毅, 岡本 修一, 田村 彰吾, 篠原 翔, 新井 信夫, 菊地 良介, 安藤 善孝, 小嶋 哲人, 松下 正

    日本血栓止血学会誌   Vol. 31 ( 4 ) page: 409 - 419   2020.8

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    INNOVANCE VWF Acは血小板膜糖蛋白質GPIbの変異体を用いるフォンヴィレブランド因子(von Willebrand factor:VWF)活性(VWF:GPIbM)測定試薬である。本研究では本邦で初めてその基本性能評価を行った。併行精度はCVが3%未満、室内再現性はCVが2%未満と良好な成績であった。希釈直線性も良好であり、最小検出感度は1.3IU/dLであった。また、干渉物質や未分画ヘパリン混入による明らかな影響は見られなかった。正常検体100例を用いた相関性試験ではVWF抗原量およびVWFリストセチンコファクター活性(VWF:RCo)と良好な相関性を示した。フォンヴィレブランド病患者検体においてもVWF:RCoとの測定値に大きな差はなく、VWF:GPIbMでは特に低濃度域を評価することが可能であった。INNOVANCE VWF AcはVWF:RCo測定試薬と比べても高い性能を有することが明らかとなった。(著者抄録)

    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J02561&link_issn=&doc_id=20200812220008&doc_link_id=10.2491%2Fjjsth.31.409&url=https%3A%2F%2Fdoi.org%2F10.2491%2Fjjsth.31.409&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  26. 凝固一段法による第VIII因子活性測定における試薬の組み合わせに関する検討 Reviewed International journal

    鈴木 敦夫, 鈴木 伸明, 兼松 毅, 岡本 修一, 田村 彰吾, 安藤 善孝, 清井 仁, 松下 正

    日本血栓止血学会誌   Vol. 31 ( 2 ) page: 231 - 231   2020.5

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  27. Higher FVIII:C measured by chromogenic substrate assay than by one-stage assay is associated with silent hemophilic arthropathy. Reviewed International journal

    Mika Ogawa, Nobuaki Suzuki, Nobunori Takahashi, Shogo Tamura, Atsuo Suzuki, Sachiko Suzuki, Yuua Hattori, Misaki Kakihara, Takeshi Kanematsu, Toshihisa Kojima, Akira Katsumi, Fumihiko Hayakawa, Tetsuhito Kojima, Naoki Ishiguro, Hitoshi Kiyoi, Tadashi Matsushita

    Thrombosis research   Vol. 188   page: 103 - 105   2020.4

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  28. Performance evaluation of Revohem™ FVIII chromogenic and Revohem™ FIX chromogenic in the CS-5100 autoanalyser. Reviewed International journal

    Atsuo Suzuki, Nobuaki Suzuki, Takeshi Kanematsu, Sho Shinohara, Nobuo Arai, Ryosuke Kikuchi, Tadashi Matsushita

    International journal of laboratory hematology   Vol. 41 ( 5 ) page: 664 - 670   2019.10

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    INTRODUCTION: Chromogenic substrate assay (CSA) reagents Revohem™ FVIII and Revohem™ FIX are now available as in vitro diagnostic reagents for autoanalysers in Japan. In this study, we evaluated the performance of these reagents in the CS-5100 automated coagulation analyser. METHODS: We assessed within-run and between-day imprecision, on-board stability and frozen-storage stability of Revohem FVIII and FIX. Sensitivity to lupus anticoagulant (LA) was examined using LA-positive patient plasma. Correlations were analysed using plasma samples from normal individuals and patients with haemophilia A (HA) or B (HB) or von Willebrand disease (VWD). RESULTS: Imprecision was <2% for Revohem FVIII and <6.5% for Revohem FIX. On-board storage of Revohem FVIII resulted in a <10% decrease in FVIII levels from baseline at 24 hours, whereas Revohem FIX showed a >10% decrease at 8 hours. Revohem FVIII showed good stability while frozen for 22 days. Although Revohem FIX showed degradation due to freeze-thawing, a new calibration improved stability up to 22 days. Interference from LA was not observed with Revohem FVIII or FIX. The FVIII CSA-CSA correlation was excellent in normal (r = 0.9924), HA (r = 0.9945) and VWD (r = 0.9914). The FVIII CSA-OSA correlation was good in normal (r = 0.8468) and excellent in HA (r = 0.975) and VWD (r = 0.9936). The FIX CSA-OSA correlation was fair in normal (r = 0.4791) and excellent in HB (r = 0.9501). CONCLUSION: Revohem FVIII and FIX both showed excellent performance in the CS-5100 analyser. These reagents could be useful in routine laboratory testing for diagnosing and treating haemophilia.

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  29. Successful Perioperative Combination of High-Dose FVIII Therapy Followed by Emicizumab in a Patient with Hemophilia A with Inhibitors. Reviewed International journal

    Shuichi Okamoto, Nobuaki Suzuki, Atsuo Suzuki, Sachiko Suzuki, Shogo Tamura, Mochihito Suzuki, Nobunori Takahashi, Toshihisa Kojima, Takeshi Kanematsu, Tetsuhito Kojima, Hitoshi Kiyoi, Naoki Ishiguro, Tadashi Matsushita

    TH open : companion journal to thrombosis and haemostasis   Vol. 3 ( 4 ) page: e364 - e366   2019.10

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    We managed perioperative hemostasis for a 72-year-old man with hemophilia A and low inhibitor titers (3 BU/mL), who underwent osteosynthesis for supracondylar fracture of the left humerus. He was treated perioperatively using the combination of high doses of factor VIII (FVIII) with recombinant human Factor VIII Fc fusion protein (rFVIIIFc), followed by emicizumab. On the day of surgery (day 0), he was administered bolus infusion of 150 IU/kg rFVIIIFc, followed by continuous infusion at a dose of 4 IU/kg/h. Emicizumab, 3 mg/kg, was injected subcutaneously once a week, on days 5, 12, 19, and 26. Inhibitors were detected on day 6 at a titer of 4 BU/mL and FVIII:C decreased to below assay sensitivity limits on day 10. The rate of increase in inhibitor titers was high, with inhibitors increasing to 343.4 BU/mL on day 14. The transition of thrombin production by thrombin generation assay (TGA) showed temporary decrease in thrombin production on day 7, although it was restored by day 10, i.e., five days after commencement of emicizumab therapy. Rotational thromboelastometry displayed consistent results with TGA, showing that clotting time was prolonged and the alpha angle decreased to less than measurable levels on day 6, although they were improved by day 10. There were no bleeding-related events or other adverse events throughout the perioperative period. In conclusion, emicizumab was effective for the management of perioperative hemostasis after development of an anamnestic response in a patient with hemophilia A with inhibitors. Combination therapy with high doses of FVIII followed by emicizumab could be a workable alternative for patients with hemophilia A with inhibitors.

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  30. 血友病Aにおけるassay discrepancy評価のための凝固一段法試薬のバリデーション Reviewed International journal

    鈴木 敦夫, 鈴木 伸明, 兼松 毅, 安藤 善孝, 松下 正

    臨床病理   Vol. 67 ( 補冊 ) page: 251 - 251   2019.10

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  31. Apparent synonymous mutation F9 c.87A>G causes secretion failure by in-frame mutation with aberrant splicing. Reviewed International journal

    Koya Odaira, Shogo Tamura, Nobuaki Suzuki, Misaki Kakihara, Yuna Hattori, Mahiru Tokoro, Sachiko Suzuki, Akira Takagi, Akira Katsumi, Fumihiko Hayakawa, Shuichi Okamoto, Atsuo Suzuki, Takeshi Kanematsu, Tadashi Matsushita, Tetsuhito Kojima

    Thrombosis research   Vol. 179   page: 95 - 103   2019.7

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    INTRODUCTION: Hemophilia B is an X-linked recessive bleeding disorder caused by coagulation factor IX (FIX) gene (F9) mutations. Several F9 synonymous mutations have been known to cause hemophilia B; however, the deleterious mechanisms underlying the development of hemophilia B have not been completely understood. To elucidate the molecular pathogenesis causing hemophilia B, we investigated the synonymous F9 mutation: c.87A>G, p.(Thr29=). MATERIALS AND METHODS: The influence of F9 c.87A>G on mRNA splicing was analyzed by exon-trap assay and in silico prediction. We prepared FIX expression vectors using mutant F9 cDNA and transfected HepG2 cells to investigate intracellular transport and extracellular secretion of FIX. Intracellular kinetics of the expressed FIX was examined by treatment with the proteasome inhibitor MG132. RESULTS: Exon-trap analysis revealed that F9 c.87A>G resulted in almost (99.1%) aberrant splicing (r.83_88del). In silico analysis predicted that F9 c.87A>G influenced the splicing pattern by generating an available aberrant 5' splice site. The aberrant F9 mRNA (r.83_88del) was translated to a mutant FIX p.Cys28_Val30delinsPhe with an in-frame mutation at the signal peptide cleavage site. Simultaneously, a small amount (0.9%) of mutant F9 r.87A>G translating into WT FIX p.Thr29 = was also observed. The mutant FIX was abnormally retained in the endoplasmic reticulum (ER) and was not extracellularly secreted. It appeared to be intracellularly degraded via proteasome-dependent degradation machinery. CONCLUSION: F9 c.87A>G was found to cause abnormal mRNA splicing, r.83_88del, and produce the mutant FIX p.Cys28_Val30delinsPhe. The mutant FIX is an abnormal protein with extracellular secretory defects and is intracellularly eliminated via proteasome-dependent ER-associated degradation.

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  32. Correction to: Thalidomide maintenance therapy in Japanese myeloma patients: a multicenter, phase II clinical trial (COMET study). Reviewed

    Hirokazu Murakami, Tetsuhiro Kasamatsu, Jun Murakami, Toru Kiguchi, Takeshi Kanematsu, Daisuke Ogawa, Hiroyuki Takamatsu, Hiroshi Handa, Shuji Ozaki, Hirokazu Miki, Takeshi Takahashi, Takaaki Takeo, Tatsuya Yamauchi, Takanobu Morishita, Hiroshi Kosugi, Kazuyuki Shimizu

    International journal of hematology   Vol. 110 ( 1 ) page: 125 - 126   2019.7

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    The authors would like to correct the errors in the publication of the original article. The correction details are given below.

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  33. Ischaemic events are rare, and the prevalence of hypertension is not high in Japanese adults with haemophilia: First multicentre study in Asia. Reviewed International journal

    Nagao A, Suzuki N, Takedani H, Yamasaki N, Chikasawa Y, Sawada A, Kanematsu T, Nojima M, Higasa S, Amano K, Fukutake K, Fujii T, Matsushita T, Suzuki T

    Haemophilia : the official journal of the World Federation of Hemophilia   Vol. 25 ( 4 ) page: E223 - E230   2019.7

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    INTRODUCTION: With the increasing life expectancy of patients with haemophilia (PWH), the number of PWH with age-related comorbidities, such as ischaemic events, is increasing. AIM: We conducted this multicentre observational study to identify the risk factors for major ischaemic events in PWH. METHODS: This study was the first multicentre observational study, conducted with the participation of five haemophilia treatment centres in Japan, conducted in ≥30-year-old adult PWH. The latest data recorded in the medical charts between 1 January and 31 December 2016 were reviewed. Healthcare data collected from the National Health and Nutrition Survey were used as the control data. RESULTS: Data of a total of 711 patients were collected. Only two PWH (0.3%) had a history of ischaemic events. Age-adjusted analysis indicated that the prevalence of hypertension defined as a blood pressure of 140/90 mm Hg or over was similar in the PWH to that in the males of the general population. However, when hypertension was defined more strictly (≥130/85 mm Hg), the prevalence was significantly lower in PWH than in the general male population. The hypertension in PWH was associated with the age, BMI, CKD, HIV infection and inhibitors. In particular, the odds ratio for the presence of inhibitors was high (odds ratio = 7.529). CONCLUSION: Whether the present results can be attributed to Japanese ethnicity or to the presence of haemophilia per se remains uncertain. We propose to initiate a prospective study for further investigation.

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  34. Molecular basis of SERPINC1 mutations in Japanese patients with antithrombin deficiency. Reviewed International journal

    Tamura S, Hashimoto E, Suzuki N, Kakihara M, Odaira K, Hattori Y, Tokoro M, Suzuki S, Takagi A, Katsumi A, Hayakawa F, Suzuki A, Okamoto S, Kanematsu T, Matsushita T, Kojima T

    Thrombosis research   Vol. 178   page: 159 - 170   2019.6

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  35. Thalidomide maintenance therapy in Japanese myeloma patients: a multicenter, phase II clinical trial (COMET study).

    Hirokazu Murakami, Tetsuhiro Kasamatsu, Jun Murakami, Toru Kiguchi, Takeshi Kanematsu, Daisuke Ogawa, Hiroyuki Takamatsu, Hiroshi Handa, Shuji Ozaki, Hirokazu Miki, Takeshi Takahashi, Takaaki Takeo, Tatsuya Yamauchi, Takanobu Morishita, Hiroshi Kosugi, Kazuyuki Shimizu

    International journal of hematology   Vol. 109 ( 4 ) page: 409 - 417   2019.4

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    A prospective, multicenter, phase II study was performed to assess the efficacy and safety of thalidomide maintenance therapy at different doses in Japanese multiple myeloma (MM) patients. This study included 34 patients (median age, 74 years) who were previously treated with not more than three prior therapies and whose response status was evaluated as at least stable disease. They were randomized into Group A (no maintenance; 12 patients), Group B (50 mg thalidomide maintenance; 12 patients), and Group C (100 mg thalidomide maintenance; 10 patients), respectively. Thalidomide maintenance therapy resulted in improved depth of response in three cases (13.6%) and sustained response after induction therapy in eight cases (36.4%). Two-year progression-free survival (PFS) was 25.0%, 33.3%, and 77.8% in Groups A, B, and C, respectively, and was significantly higher in Group C than in Group A (p = 0.005). There was no difference in the incidence of hematological or non-hematological adverse events between Groups B and C. The current study demonstrates that maintenance with daily thalidomide at 100 mg, but not 50 mg, improved depth of response and prolonged PFS, and that this treatment was feasible for use in Japanese MM patients.

    DOI: 10.1007/s12185-019-02607-z

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  36. Clot waveform analysis in Clauss fibrinogen assay contributes to classification of fibrinogen disorders International journal

    Suzuki Atsuo, Suzuki Nobuaki, Kanematsu Takeshi, Shinohara Sho, Arai Nobuo, Kikuchi Ryosuke, Matsushita Tadashi

    THROMBOSIS RESEARCH   Vol. 174   page: 98 - 103   2019.2

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    BACKGROUND: Clauss fibrinogen assay (CFA) is widely used as a screening test to detect fibrinogen disorders. However, CFA alone cannot distinguish quantitative and qualitative defects because it depends on functional fibrinogen activity (Ac), and fibrinogen antigen (Ag) determination is required to classify fibrinogen disorders. OBJECTIVES: To establish a novel approach to classify fibrinogen disorders, we investigated the potential of clot waveform analysis (CWA) of CFA and searched for a surrogate marker for fibrinogen Ag. MATERIALS AND METHODS: We analyzed CWA parameters obtained from CFA using plasma from normal patients (n = 91) and those with fibrinogen disorders (n = 27, including 15 hypofibrinogenemia, 6 dysfibrinogenemia and 6 hypodysfibrinogenemia) with a CS-5100 autoanalyzer. RESULTS: We found that maximum coagulation velocity (Min1) levels were most strongly correlated with fibrinogen Ag in both normal and fibrinogen disorders. Hence, Min1 appeared to function as a surrogate for fibrinogen Ag. Although the Ac/Min1 ratio did not simply reflect the measured Ac/Ag ratio, we found that the Ac/Min1 ratio was significantly higher than normal in hypofibrinogenemia and hypodysfibrinogenemia, but not in dysfibrinogenemia. On the other hand, we could distinguish type II deficiency from type I using estimated fibrinogen Ag (eAg) predicted from Min1. The Ac/eAg ratios of dysfibrinogenemia and hypodysfibrinogenemia were significantly lower than those of normal and hypofibrinogenemia. CONCLUSION: The CWA of CFA could distinguish fibrinogen disorders using a combination of Ac/Min1 and Ac/eAg values. This analysis allows the qualitative detection of fibrinogen disorder easily and represents a novel screening test for fibrinogen disorders.

    DOI: 10.1016/j.thromres.2018.12.018

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  37. 凝固波形解析を利用した新しい異常フィブリノゲン血症検出法 Reviewed International journal

    鈴木 敦夫, 篠原 翔, 新井 信夫, 兼松 毅, 鈴木 伸明, 安藤 善孝, 松下 正

    日本検査血液学会雑誌   Vol. 19 ( 学術集会 ) page: S166 - S166   2018.6

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  38. Ischemic events are rare among aging patients with hemophilia: Results of a cross-sectional study from at centers treating hemophiliacs in Japan Reviewed International journal

    Suzuki Nobuaki, Takedani Hideyuki, Yamasaki Naoya, Chikasawa Yushi, Sawada Akihiro, Kanematsu Takeshi, Higasa Satoshi, Amano Kagehiro, Fukutake Katsuyuki, Nagao Azusa

    HAEMOPHILIA   Vol. 24   page: 13-14   2018.5

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  39. 凝固一段法と合成基質法による第VIII因子活性測定において乖離を示した血友病A症例 Reviewed International journal

    鈴木 敦夫, 鈴木 伸明, 兼松 毅, 岸本 磨由子, 田村 彰吾, 高木 明, 川上 萌, 梶浦 容子, 小嶋 哲人, 松下 正

    日本血栓止血学会誌   Vol. 29 ( 2 ) page: 210 - 210   2018.5

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  40. Vwf K1362A resulted in failure of protein synthesis in mice.

    Naomi Sanda, Nobuaki Suzuki, Atsuo Suzuki, Takeshi Kanematsu, Mayuko Kishimoto, Hidetoshi Hasuwa, Akira Takagi, Tetsuhito Kojima, Tadashi Matsushita, Shigeo Nakamura

    International journal of hematology   Vol. 107 ( 4 ) page: 428 - 435   2018.4

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    Von Willebrand factor (VWF) is synthesized in megakaryocytes and endothelial cells (ECs) and has two main roles: to carry and protect coagulation factor VIII (FVIII) from degradation by forming VWF-FVIII complex; and to mediate platelet adhesion and aggregation at sites of vascular injury. Previous research using the HEK293 cell line revealed that the VWF K1362 mutation interacted directly with platelet glycoprotein Ib (GPIb). Vwf K1362A knock-in (KI) mice were therefore generated to verify the in vivo function of residue 1362 in binding to platelet GPIb. The Cre-loxP system was employed to introduce the Vwf K1362A mutation systemically in mice. In blood coagulation analysis, the VWF antigen (VWF:Ag) of Lys1362Ala KI homozygous (homo) mice was below the sensitivity of detection by enzyme-linked immunosorbent assay. FVIII activities (FVIII:C) were 47.9 ± 0.3 and 3.3 ± 0.3% (K1362A heterozygous (hetero) and K1362A KI homo mice, respectively) compared to wild-type mice. Immunohistochemical staining analysis revealed that VWF protein did not exist in ECs of K1362A KI homo mice. These results indicated that VWF protein synthesis of K1362A was impaired after transcription in mice. K1362 seems to represent a very important position not only for VWF function, but also for VWF synthesis in mice.

    DOI: 10.1007/s12185-017-2394-y

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  41. Combined deficiency of factors V and VIII by chance coinheritance of parahaemophilia and haemophilia A, but not by mutations of either LMAN1 or MCFD2, in a Japanese family International journal

    S. Suzuki, Y. Nakamura, N. Suzuki, T. Yamazaki, Y. Takagi, S. Tamura, A. Takagi, T. Kanematsu, T. Matsushita, T. Kojima

    Haemophilia   Vol. 24 ( 1 ) page: e13 - e16   2018.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Blackwell Publishing Ltd  

    DOI: 10.1111/hae.13360

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  42. その他の凝固因子濃縮製剤の使い方(フィブリノゲン製剤など) International journal

    兼松 毅

    日本血栓止血学会誌   Vol. 29 ( 6 ) page: 744-747 - 747   2018

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:一般社団法人 日本血栓止血学会  

    DOI: 10.2491/jjsth.29.744

    CiNii Research

  43. 凝固波形解析による異常フィブリノゲン血症の新規検出法 Reviewed International journal

    鈴木 敦夫, 岸本 磨由子, 兼松 毅, 小川 実加, 鈴木 伸明, 松下 正

    日本血栓止血学会誌   Vol. 28 ( 2 ) page: 212 - 212   2017.4

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  44. 合成基質法と凝固一段法による凝固第VIII因子製剤測定値の比較検討 Reviewed International journal

    鈴木 敦夫, 鈴木 伸明, 岸本 磨由子, 兼松 毅, 小川 実加, 松下 正

    日本血栓止血学会誌   Vol. 28 ( 2 ) page: 185 - 185   2017.4

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  45. Retrospective analysis of in vivo recovery and clearance during continuous infusion of recombinant factor VIII products: a single-institution study International journal

    N. Suzuki, A. Hirakawa, M. Kishimoto, T. Kanematsu, M. Ogawa, H. Kiyoi, T. Matsushita

    HAEMOPHILIA   Vol. 23 ( 2 ) page: 215 - 221   2017.3

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    Background: Continuous infusion (CI) of recombinant FVIII (rFVIII) concentrates has been reported as an effective and safe method to achieve haemostasis during major surgeries or severe bleeding events. For more effective and safer CI, better understanding of in vivo recovery (IVR) and clearance (CL) issues is imperative. Objective: We investigated the following factors affecting IVR and CL using univariate and multivariate regression analyses during 47 CIs in 34 patients: rFVIII concentrate type, haemophilia severity, blood type, the presence of hepatitis C virus (HCV) or human immunodeficiency virus (HIV), age and body mass index (BMI). Results: The mean IVR was 1.64 +/- 0.49 IU dL(-1) per IU kg(-1), and the mean CL during CI was 3.56 +/- 1.57 mL h(-1) kg(-1). The univariate and multivariate regression analyses showed that the CL of octocog alfa was significantly lower than that of rurioctocog alfa (P = 0.043 and 0.0034, respectively). There was a significant difference in BMI in the univariate and multivariate regression analyses (P = 0.0403 and 0.0376, respectively). Conclusions: This study indicated that CL during CI was potentially affected by the type of rFVIII concentrate used and BMI.

    DOI: 10.1111/hae.13082

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  46. 凝固波形を用いたClauss法による異常フィブリノゲン検出と妥当性評価 Reviewed International journal

    鈴木 敦夫, 岸本 磨由子, 兼松 毅, 杉浦 由姫乃, 亀山 なつみ, 高津 真由美, 鈴木 伸明, 松本 祐之, 松下 正

    日本血栓止血学会誌   Vol. 27 ( 2 ) page: 216 - 216   2016.5

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  47. The first case of antithrombin-resistant prothrombin Belgrade mutation in Japanese. Reviewed International journal

    Mayuko Kishimoto, Nobuaki Suzuki, Moe Murata, Mika Ogawa, Takeshi Kanematsu, Akira Takagi, Hitoshi Kiyoi, Tetsuhito Kojima, Tadashi Matsushita

    Annals of hematology   Vol. 95 ( 3 ) page: 541 - 542   2016.2

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    DOI: 10.1007/s00277-015-2533-6

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  48. A case of MYH9 disorders caused by a novel mutation (p.K74E) Reviewed International journal

    Takeshi Kanematsu, Nobuaki Suzuki, Tadao Yoshida, Mayuko Kishimoto, Tomohiro Aoki, Mika Ogawa, Yoshitoyo Kagami, Hitoshi Kiyoi, Tadashi Matsushita, Shinji Kunishima

    ANNALS OF HEMATOLOGY   Vol. 95 ( 1 ) page: 161 - 163   2016.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:SPRINGER  

    DOI: 10.1007/s00277-015-2506-9

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  49. Clinical Course and Management of Surgical Emergency in a Severe Hemophilia a Patient Under Weekly Subcutaneous Administration of a Bispecific Antibody to Factors IXa and X (ACE910) Reviewed International journal

    Takeshi Kanematsu, Nobuaki Suzuki, Naomi Sanda, Mika Ogawa, Mayuko Kishimoto, Atsuo Suzuki, Hitoshi Kiyoi, Ryu Kasai, Tadashi Matsushita

    BLOOD   Vol. 126 ( 23 )   2015.12

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    DOI: 10.1182/blood.V126.23.2868.2868

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  50. Genetic Analysis of Von Willebrand Disease By Using the Exome Sequencing Approach Reviewed International journal

    Naomi Sanda, Nobuaki Suzuki, Takeshi Kanematsu, Mika Ogawa, Mayuko Kishimoto, Shigeo Nakamura, Tadashi Matsushita

    BLOOD   Vol. 126 ( 23 )   2015.12

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Books 12

  1. 専門医のための血液病学 Reviewed

    兼松 毅、松下 正、他( Role: Joint author)

    株式会社 医学書院  2022.3  ( ISBN:978-4-260-04772-2

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    Total pages:456   Responsible for pages:306-308   Language:Japanese Book type:Textbook, survey, introduction

  2. 専門医のための血液病学 Reviewed

    兼松 毅, 松下 正( Role: Joint author)

    株式会社 医学書院  2022.3  ( ISBN:9784260047722

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    Total pages:456   Responsible for pages:306-308   Language:Japanese Book type:Textbook, survey, introduction

  3. スタンダード検査血液学 第4版 Reviewed

    兼松 毅、松下 正、他( Role: Joint author)

    医歯薬出版株式会社  2021.5  ( ISBN:978-4-263-22691-9

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    Total pages:515   Responsible for pages:78-79,197-198, 406-411   Language:Japanese Book type:Textbook, survey, introduction

  4. スタンダード検査血液学 第4版 Reviewed

    兼松 毅, 松下 正( Role: Joint author)

    医歯薬出版株式会社  2021.5  ( ISBN:9784263226919

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    Total pages:515   Responsible for pages:78-79,197-198, 406-411   Language:Japanese Book type:Textbook, survey, introduction

  5. ICU治療指針 Ⅱ Reviewed

    兼松 毅、松下 正、他( Role: Joint author)

    株式会社 総合医学社  2019.12  ( ISBN:978-4-88378-563-6

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    Total pages:528   Responsible for pages:951-958   Language:Japanese Book type:Textbook, survey, introduction

  6. ICU治療指針 Ⅱ Reviewed

    兼松 毅, 松下 正( Role: Joint author)

    株式会社 総合医学社  2019.12  ( ISBN:9784883785636

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    Total pages:528   Responsible for pages:951-958   Language:Japanese Book type:Textbook, survey, introduction

  7. 未来型血液治療学 Reviewed

    兼松 毅、松下 正、他( Role: Joint author)

    株式会社中外医学社  2019.10  ( ISBN:978-4-498-22518-3

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    Total pages:254   Responsible for pages:246-252   Language:Japanese Book type:Textbook, survey, introduction

  8. 未来型血液治療学 Reviewed

    兼松 毅, 松下 正( Role: Joint author)

    株式会社中外医学社  2019.10  ( ISBN:9784498225183

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    Total pages:254   Responsible for pages:246-252   Language:Japanese Book type:Textbook, survey, introduction

  9. 血液疾患最新の治療2017-2019 Reviewed

    兼松 毅、小嶋 哲人、他( Role: Joint author)

    株式会社南江堂  2017.2  ( ISBN:978-4-524-25422-4

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    Total pages:378   Responsible for pages:248-251   Language:Japanese Book type:Textbook, survey, introduction

  10. 血液疾患最新の治療2017-2019 Reviewed

    兼松 毅, 小嶋 哲人( Role: Joint author)

    株式会社南江堂  2017.2  ( ISBN:9784524254224

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    Total pages:378   Responsible for pages:248-251   Language:Japanese Book type:Textbook, survey, introduction

  11. EBM血液疾患の治療2015-2016 Reviewed

    兼松 毅、松下 正、他( Role: Joint author)

    株式会社中外医学社  2014.10  ( ISBN:978-4-498-12582-7

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    Total pages:556   Responsible for pages:424-429   Language:Japanese Book type:Textbook, survey, introduction

  12. EBM血液疾患の治療2015-2016 Reviewed

    兼松 毅, 松下 正( Role: Joint author)

    株式会社中外医学社  2014.10  ( ISBN:9784498125827

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    Total pages:556   Responsible for pages:424-429   Language:Japanese Book type:Textbook, survey, introduction

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MISC 3

  1. 血友病Bにおける血液凝固第IX因子遺伝子変異とインヒビターの関連性の検討

    坂根 寛人, 田村 彰吾, 橋本 恵梨華, 藤岡 亮也, 槇山 愛弓, 河村 奈美, 鈴木 幸子, 高木 夕希, 高木 明, 兼松 毅, 岸本 磨由子, 小川 実加, 鈴木 伸明, 松下 正, 矢田 弘史, 嶋 緑倫, 小嶋 哲人

    日本血栓止血学会誌   Vol. 28 ( 2 ) page: 188 - 188   2017.4

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  2. Clinical Course and Management of Surgical Emergency in a Severe Hemophilia a Patient Under Weekly Subcutaneous Administration of a Bispecific Antibody to Factors IXa and X (ACE910)

    Takeshi Kanematsu, Nobuaki Suzuki, Naomi Sanda, Mika Ogawa, Mayuko Kishimoto, Atsuo Suzuki, Hitoshi Kiyoi, Ryu Kasai, Tadashi Matsushita

    BLOOD   Vol. 126 ( 23 )   2015.12

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:AMER SOC HEMATOLOGY  

    Web of Science

  3. Genetic Analysis of Von Willebrand Disease By Using the Exome Sequencing Approach

    Naomi Sanda, Nobuaki Suzuki, Takeshi Kanematsu, Mika Ogawa, Mayuko Kishimoto, Shigeo Nakamura, Tadashi Matsushita

    BLOOD   Vol. 126 ( 23 )   2015.12

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Presentations 20

  1. Clinical Course and Management of Surgical Emergency in a Severe Hemophilia a Patient Under Weekly Subcutaneous Administration of a Bispecific Antibody to Factors IXa and X (ACE910) International conference

    Kanematsu Takeshi, Suzuki Nobuaki, Sanda Naomi, Ogawa Mika, Kishimoto Mayuko, Suzuki Atsuo, Kiyoi Hitoshi, Kasai Ryu, Matsushita Tadashi

    米国血液学会総会  2015.12.3 

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    Country:United States  

  2. A case of MYH9 disorders caused by a novel mutation (p.K74E) International conference

    Takeshi KANEMATSU, Nobuaki SUZUKI, Mayuko KISHIMOTO, Tomohiro AOKI, Mika Ogawa, Yoshitoyo KAGAMI, Shinji KUNISHIMA, Hitoshi KIYOI, Tadashi MATSUSHITA

    International Society on Thrombosis and Haemostasis 2015 Congress  2015.6.22 

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    Country:Canada  

  3. Myh9 R702C is associated with altered erythropoiesis in mice

    Takeshi Kanematsu, Nobuaki Suzuki, Atsuo Suzuki, Shogo Tamura, Shuichi Okamoto, Yuichi Ishikawa, Akira Katsumi, Hitoshi Kiyoi, Hidehiko Saito, Shinji Kunishima, Tetsuhito Kojima, Tadashi Matsushita

    2019.10.13 

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    Country:Japan  

  4. Continuous infusion of recombinant factor IX Fc fusion protein during major surgery International conference

    Takeshi Kanematsu, Nobuaki Suzuki, Mika Ogawa, Mayuko Kishimoto, Atsuo Suzuki, Hitoshi Kiyoi, Tetsuhito Kojima, Tadashi Matsushita

    XXVI Congress of the International Society on Thrombosis and Haemostasis  2017.7.11 

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    Country:Germany  

  5. A case of MYH9 disorders caused by a novel mutation (p.K74E) International conference

    Takeshi KANEMATSU, Nobuaki SUZUKI, Mayuko KISHIMOTO, Tomohiro AOKI, Mika Ogawa, Yoshitoyo KAGAMI, Shinji KUNISHIMA, Hitoshi KIYOI, Tadashi MATSUSHITA

    International Society on Thrombosis and Haemostasis 2015 Congress  2015.6.22 

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    Country:Canada  

  6. Myh9 R702C is associated with altered erythropoiesis in mice

    Takeshi Kanematsu, Nobuaki Suzuki, Atsuo Suzuki, Shogo Tamura, Shuichi Okamoto, Yuichi Ishikawa, Akira Katsumi, Hitoshi Kiyoi, Hidehiko Saito, Shinji Kunishima, Tetsuhito Kojima, Tadashi Matsushita

    2019.10.13 

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    Country:Japan  

  7. Continuous infusion of recombinant factor IX Fc fusion protein during major surgery International conference

    Takeshi Kanematsu, Nobuaki Suzuki, Mika Ogawa, Mayuko Kishimoto, Atsuo Suzuki, Hitoshi Kiyoi, Tetsuhito Kojima, Tadashi Matsushita

    XXVI Congress of the International Society on Thrombosis and Haemostasis  2017.7.11 

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    Country:Germany  

  8. Clinical Course and Management of Surgical Emergency in a Severe Hemophilia a Patient Under Weekly Subcutaneous Administration of a Bispecific Antibody to Factors IXa and X (ACE910) International conference

    Kanematsu Takeshi, Suzuki Nobuaki, Sanda Naomi, Ogawa Mika, Kishimoto Mayuko, Suzuki Atsuo, Kiyoi Hitoshi, Kasai Ryu, Matsushita Tadashi

    米国血液学会総会  2015.12.3 

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    Country:United States  

  9. 21か月の経過で自然寛解した高力価インヒビター保有自己免疫性第V因子欠乏症(AiF5D)の1例

    兼松 毅、鈴木 伸明、岡本 修一、尾崎 司、惣宇利 正善、鈴木 敦夫、田村 彰吾、 早川 文彦、小嶋 哲人、清井 仁、一瀬 白帝、松下 正

    第83回日本血液学会学術集会  2021.9.23  張替 秀郎(東北大学)

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    Venue:完全Web開催  

  10. 21か月の経過で自然寛解した高力価インヒビター保有自己免疫性第V因子欠乏症(AiF5D)の1例

    兼松 毅, 鈴木 伸明, 岡本 修一, 尾崎 司, 惣宇利 正善, 鈴木 敦夫, 田村 彰吾, 早川 文彦, 小嶋 哲人, 清井 仁, 一瀬 白帝, 松下 正

    第83回日本血液学会学術集会  2021.9.23  張替 秀郎(東北大学)

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    Venue:完全Web開催  

  11. 周術期の⽌⾎に難渋した先天性第V因⼦⽋乏症の1例

    兼松 毅、鈴木 伸明、岡本 修一、鈴木 敦夫、田村 彰吾、早川 文彦、小嶋 哲人、清井 仁、松下 正

    第43回日本血栓止血学会学術集会  2021.5.28  浅田 祐士郎

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    Event date: 2021.5

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    Venue:宮崎県   Country:Japan  

  12. 周術期の⽌⾎に難渋した先天性第V因⼦⽋乏症の1例

    兼松 毅, 鈴木 伸明, 岡本 修一, 鈴木 敦夫, 田村 彰吾, 早川 文彦, 小嶋 哲人, 清井 仁, 松下 正

    第43回日本血栓止血学会学術集会  2021.5.28  浅田 祐士郎

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    Event date: 2021.5

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:宮崎県   Country:Japan  

  13. Genetic Analysis of Von Willebrand Disease By Using the Exome Sequencing Approach International conference

    Sanda Naomi, Suzuki Nobuaki, Kanematsu Takeshi, Ogawa Mika, Kishimoto Mayuko, Nakamura Shigeo, Matsushita Tadashi

    米国血液学会総会  2015.12.3 

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    Language:English   Presentation type:Poster presentation  

    Country:United States  

  14. 当施設における新生児・乳幼児に対するエミシズマブの使用経験

    兼松 毅、鈴木 伸明、岡本 修一、鈴木 敦夫、田村 彰吾、早川 文彦、小嶋 哲人、清井 仁、松下 正

    日本血栓止血学会学術集会  2020.6 

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    Language:Japanese  

  15. 特発性血小板減少性紫斑病の病勢に対し、サイトメガロウイルス再活性化の関与が疑われた2例

    兼松 毅、鈴木 伸明、岡本 修一、鈴木 敦夫、川上 萌、三田 直美、田村 彰吾、小嶋 哲人、清井 仁、松下 正

    日本血栓止血学会学術集会  2019.6.20 

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    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  16. ループスアンチコアグラント低プロトロンビン血症症候群(LAHPS)の2例

    兼松 毅、鈴木 伸明、鈴木 敦夫、高木 明、岸本 磨由子、川上(村田) 萌、三田 直美、小山 大輔、小嶋 哲人、清井 仁、松下 正

    日本血栓止血学会学術集会  2018.6.28 

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    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  17. Genetic Analysis of Von Willebrand Disease By Using the Exome Sequencing Approach International conference

    Sanda Naomi, Suzuki Nobuaki, Kanematsu Takeshi, Ogawa Mika, Kishimoto Mayuko, Nakamura Shigeo, Matsushita Tadashi

    米国血液学会総会  2015.12.3 

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    Language:English   Presentation type:Poster presentation  

    Country:United States  

  18. 特発性血小板減少性紫斑病の病勢に対し、サイトメガロウイルス再活性化の関与が疑われた2例

    兼松 毅, 鈴木 伸明, 岡本 修一, 鈴木 敦夫, 川上 萌, 三田 直美, 田村 彰吾, 小嶋 哲人, 清井 仁, 松下 正

    日本血栓止血学会学術集会  2019.6.20 

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    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

  19. 当施設における新生児・乳幼児に対するエミシズマブの使用経験

    兼松 毅, 鈴木 伸明, 岡本 修一, 鈴木 敦夫, 田村 彰吾, 早川 文彦, 小嶋 哲人, 清井 仁, 松下 正

    日本血栓止血学会学術集会  2020.6 

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    Language:Japanese  

  20. ループスアンチコアグラント低プロトロンビン血症症候群(LAHPS)の2例

    兼松 毅, 鈴木 伸明, 鈴木 敦夫, 高木 明, 岸本 磨由子, 川上(村田) 萌, 三田 直美, 小山 大輔, 小嶋 哲人, 清井 仁, 松下 正

    日本血栓止血学会学術集会  2018.6.28 

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    Language:Japanese   Presentation type:Poster presentation  

    Country:Japan  

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Works 2

  1. 遺伝子治療 導入決定から投与初期までの診療におけるポイント

    兼松 毅

    2022

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    Work type:Educational material   Location:オンライン  

  2. 遺伝子治療 導入決定から投与初期までの診療におけるポイント

    兼松 毅

    2022

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    Work type:Educational material   Location:オンライン  

 

Social Contribution 8

  1. 日本血栓止血学会第10回教育セミナー

    Role(s):Lecturer, Organizing member

    日本血栓止血学会  2022.11

  2. 日本血栓止血学会第10回教育セミナー

    Role(s):Lecturer, Organizing member

    日本血栓止血学会  2022.11

  3. 日本血栓止血学会第9回教育セミナー

    Role(s):Lecturer, Organizing member

    日本血栓止血学会  2021.11

  4. 日本血栓止血学会第9回教育セミナー

    Role(s):Lecturer, Organizing member

    日本血栓止血学会  2021.11

  5. 日本血栓止血学会第8回教育セミナー

    Role(s):Lecturer, Organizing member

    2020.11

  6. 日本血栓止血学会第8回教育セミナー

    Role(s):Lecturer, Organizing member

    2020.11

  7. 日本血栓止血学会第7回教育セミナー

    Role(s):Lecturer, Organizing member

    2019.10

  8. 日本血栓止血学会第7回教育セミナー

    Role(s):Lecturer, Organizing member

    2019.10

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