研究者詳細 - 兼松　毅

Clinical course and prognosis of patients with hepatocellular carcinoma and haemophilia 査読有り国際誌

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 35 巻 ( 10 ) 頁： 1211 - 1215 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

The usefulness of tranexamic acid for bleeding symptoms of chronic consumptive coagulopathy complicated by aortic disease: a single-institute, retrospective study of 14 patients 査読有り国際誌

Suzuki, N; Suzuki, N; Kawaguchi, Y; Okamoto, S; Kanematsu, T; Katsumi, A; Suzuki, A; Tamura, S; Kojima, T; Kiyoi, H; Matsushita, T

THROMBOSIS JOURNAL 21 巻 ( 1 ) 頁： 10 - 10 2023年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Thrombosis Journal

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

Bursitis, Bacteremia, and Disseminated Infection of Mycobacteroides (Mycobacterium) abscessus subsp. massiliense 国際誌

Oka, K; Morioka, H; Eguchi, M; Sato, Y; Tetsuka, N; Iguchi, M; Kanematsu, T; Fukano, H; Hoshino, Y; Kiyoi, H; Yagi, T

INTERNAL MEDICINE 60 巻 ( 18 ) 頁： 3041 - 3045 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本内科学会

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. Mycobacteroides abscessus subsp. massiliense was isolated from the abscess and blood culture. Combination therapy (imipenem/cilastatin, amikacin, and clarithromycin) was administered for a month. Two months later, M. massiliense 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, M. massiliense was isolated from a blood culture, and she expired due to multiple organ failure.

DOI： 10.2169/internalmedicine.6189-20

[Lupus anticoagulant-hypoprothrombinemia syndrome associated with follicular lymphoma]. 査読有り国際誌

Koyama D, Hanajiri R, Kanematsu T, Ito R, Yamamoto S, Imoto N, Suzuki N, Kurahashi S, Sugiura I

[Rinsho ketsueki] The Japanese journal of clinical hematology 61 巻 ( 7 ) 頁： 745 - 749 2020年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本血液学会

56歳女性。繰り返す四肢の腫脹，疼痛，紫斑を主訴に受診した。PTとAPTTの延長を認め，クロスミキシング試験で凝固阻害因子の存在が疑われた。ループスアンチコアグラント（LA）陽性かつプロトロンビン活性著減を認め，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）と診断した。基礎疾患の検索にて胸骨背面の腫瘤を認め生検を予定したが，新鮮凍結血漿の投与で凝固異常を補正できず断念した。Prednisolone（PSL）1 mg/kgの投与により凝固異常は正常化し，LAと腫瘤も消失した。LAHPSの再発なくPSLを漸減したが，経過観察のCTで多発リンパ節腫大を認め，生検により濾胞性リンパ腫と診断した。LAHPSが再発する可能性を考慮しbendamustine＋rituximab療法を6サイクル行った。濾胞性リンパ腫は完全寛解となりLAHPSの再発も認めない。LAHPSはLA陽性だが出血傾向を来しうる稀な後天性凝固異常である。診断時はリンパ性腫瘍を含む基礎疾患の検索を要する。

DOI： 10.11406/rinketsu.61.745

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」の基本性能評価国際誌

CiNii Research

J-GLOBAL

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 31 巻 ( 4 ) 頁： 409 - 419 2020年

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：一般社団法人日本血栓止血学会

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1.3 IU/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．

DOI： 10.2491/jjsth.31.409

CiNii Research

Ischemic events are rare among aging patients with hemophilia: Results of a cross-sectional study from at centers treating hemophiliacs in Japan 査読有り国際誌

Suzuki, N; Takedani, H; Yamasaki, N; Chikasawa, Y; Sawada, A; Kanematsu, T; Higasa, S; Amano, K; Fukutake, K; Nagao, A

HAEMOPHILIA 24 巻頁： 13 - 14 2018年5月

病気のはなしハイド症候群査読有り国際誌

兼松毅, 松下正

検査と技術 42 巻 ( 11 ) 頁： 1188 - 1192 2014年10月

PDPN/CLEC-2 axis modulates megakaryocyte subtypes in a hematopoietic stem cell-regulating megakaryocyte-dominant manner 査読有り国際誌

Nara, R; Notoh, H; Sasaki, T; Tsukiji, N; Shirai, T; Kamata, A; Suzuki, N; Suzuki, A; Okamoto, S; Kanematsu, T; Suzuki, N; Katsumi, A; Kojima, T; Suzuki-Inoue, K; Matsushita, T; Tamura, S

THROMBOSIS RESEARCH 245 巻頁： 109230 - 109230 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Thrombosis Research

Introduction: Megakaryocytes are classified into several subtypes including LSP1-positive immune-skewed, MYLK4-positive hematopoietic stem cell (HSC)-regulating, and BMAL1-positive platelet-producing megakaryocytes. Podoplanin (PDPN)-expressing stromal cells generate a microenvironment that promotes megakaryopoiesis in the bone marrow. In this context, PDPN interacts with C-type lectin-like receptor-2 (CLEC-2) on megakaryocyte progenitors, which induces megakaryocyte proliferation. However, the megakaryocyte subtypes developed by the regulation of the PDPN/CLEC-2 axis have not yet been elucidated. Materials and methods: We established an immortalized bone marrow PDPN-expressing stromal cell line and a PDPN-knockout line (PDPN WT and KO feeder cells, respectively). Bone marrow hematopoietic progenitors were committed to megakaryocytes in co-culture with PDPN WT or KO feeder cells. The number and ploidy of megakaryocytes, resultant platelets, and the polarization of megakaryocyte subtypes were investigated. Results: The number of megakaryocytes was significantly increased in the co-culture with PDPN WT feeder cells compared to that with PDPN KO feeder cells. The megakaryocytes on the PDPN WT and KO feeders showed their main ploidy at 16 N∼32 N and 8 N∼16 N, respectively. The number of platelets was decreased in the co-culture with the PDPN WT feeder compared to that in the co-culture with the PDPN KO feeder. For each megakaryocyte subtype, the percentage of MYLK4-positive megakaryocytes significantly increased and the percentage of BMAL1-positive megakaryocytes significantly decreased when co-cultured with the PDPN WT feeder. These results were also confirmed in the co-culture of CLEC-2 conditional KO megakaryocytes with PDPN WT feeder cells. Conclusion: The PDPN/CLEC-2 axis modulates megakaryocyte subtype differentiation, with a predominance of HSC-regulating megakaryocytes.

DOI： 10.1016/j.thromres.2024.109230

Misleading antigenic von Willebrand factor levels in acquired von Willebrand syndrome secondary to monoclonal gammopathy of undetermined significance 査読有り

Okamoto, S; Suzuki, A; Tamura, S; Suzuki, N; Kanematsu, T; Suzuki, N; Kawaguchi, Y; Katsumi, A; Hayakawa, F; Kiyoi, H; Kojima, T; Matsushita, T

INTERNATIONAL JOURNAL OF HEMATOLOGY 121 巻 ( 1 ) 頁： 131 - 136 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Hematology

In the diagnosis and treatment of acquired von Willebrand syndrome (AVWS), von Willebrand factor (VWF) antigen levels (VWF:Ag) are helpful for quantifying blood VWF-protein levels. Most clinical laboratories measure VWF:Ag by latex immunoassay (LIA), but underlying diseases of AVWS may influence LIA results. A 60 year-old AVWS patient with immunoglobulin G (IgG) kappa-type monoclonal gammopathy of undetermined significance (MGUS) showed reduced VWF activity but normal levels of VWF:Ag. His VWF multimers were broadly decreased, which represented a large discrepancy with VWF:Ag. To investigate the mechanism of this discrepancy, we measured the patient’s plasma VWF:Ag by in-house enzyme-linked immunosorbent assay (ELISA) and LIA. We also purified the IgG fraction from the patient’s serum and measured VWF:Ag in VWF-deficient plasma supplemented with this fraction. VWF:Ag measured by in-house ELISA (VWF:AgELISA) was much lower than that measured by LIA (VWF:AgLIA), which indicated reduced VWF-protein volume in blood. Indeed, VWF:Ag was detected by LIA in VWF-deficient plasma spiked with a patient-derived IgG fraction. These results suggest that LIA detected a non-specific immunoreaction and overestimated the patient’s VWF:AgLIA. Clinicians should be aware that underlying diseases of AVWS could influence the LIA system, and interpret VWF:Ag cautiously.

DOI： 10.1007/s12185-024-03861-6

Prevalence Estimation of Dysfibrinogenemia Using the Clauss-CWA Approach 査読有り国際誌

Suzuki, A; Suzuki, N; Okamoto, S; Tamura, S; Kanematsu, T; Kikuchi, R; Kojima, T; Matsushita, T

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Laboratory Hematology

Introduction: The actual prevalence of the qualitative fibrinogen abnormalities dysfibrinogenemia and hypodysfibrinogenemia is unknown. The major reasons are that patients with dysfibrinogenemia are frequently asymptomatic, and a recommended screening test, the Clauss fibrinogen assay, cannot completely distinguish qualitative from quantitative abnormalities. We previously established a high-throughput screening test (Clauss-CWA) to identify dysfibrinogenemia with high specificity and sensitivity by the Clauss fibrinogen assay alone. Aim and Methods: This was a single-center, observational study to estimate the prevalence of dysfibrinogenemia using Clauss-CWA technology. A total of 25 471 patients in Nagoya University Hospital were screened to identify patients with suspected dysfibrinogenemia. The suspected patients were investigated by further confirmatory analyses, such as antigenic fibrinogen determination, reptilase time, fibrin polymerization analysis, and scanning electron microscopy. Results and Conclusions: Of the 25 471 enrolled patients, five with suspected dysfibrinogenemia were identified. Unfortunately, one patient was not confirmed due to a lack of plasma samples. The ratio of functional to antigenic fibrinogen was decreased, and the reptilase time was prolonged in the four patients. Interestingly, two of them showed normal functional fibrinogen levels due to acute inflammatory responses. Fibrin polymerization was impaired, and structural abnormalities were found in the fibrinogen from the patients. In some cases, functional fibrinogen levels may not be effective for identifying functional fibrinogen abnormalities. Further nationwide studies are needed to more precisely understand the epidemiology of dysfibrinogenemia.

DOI： 10.1111/ijlh.14408

Newly diagnosed multiple myeloma with bleeding and coagulation abnormalities caused by a thrombin-inhibiting substance 査読有り国際誌

Ohara, F; Suzuki, A; Suzuki, N; Kanematsu, T; Okamoto, S; Tamura, S; Kiyoi, H; Matsushita, T; Katsumi, A

INTERNATIONAL JOURNAL OF HEMATOLOGY 120 巻 ( 6 ) 頁： 743 - 749 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Hematology

Approximately 7% of patients with newly diagnosed multiple myeloma (MM) experience bleeding complications with varying causes, but few reports have described these complications. Here we report the case of a patient with newly diagnosed MM who presented with a bleeding tendency and various coagulation abnormalities. Chromogenic assays, thrombin time, and reptilase time revealed the presence of a thrombin-inhibiting substance that inhibited release of fibrinopeptide A from fibrinogen. The coagulation abnormalities improved after treatment with daratumumab, lenalidomide, and dexamethasone. As the thrombin inhibition mechanism remains unclear, no previous studies have reported recent treatment outcomes in older patients producing thrombin-inhibiting substances, which can hinder clinical treatment. Therefore, we believe that the diagnosis and the treatment course of this case provide valuable information. Moreover, such case reports provide significant insights into the pathophysiology of bleeding complications associated with MM.

DOI： 10.1007/s12185-024-03849-2

その他リンク： https://link.springer.com/article/10.1007/s12185-024-03849-2/fulltext.html

Variability in combinations of APTT reagent and substrate plasma for a one-stage clotting assay to measure factor VIII products 査読有り国際誌

Suzuki, A; Suzuki, N; Kanematsu, T; Okamoto, S; Suzuki, N; Tamura, S; Kikuchi, R; Katsumi, A; Kojima, T; Matsushita, T

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY 46 巻 ( 4 ) 頁： 705 - 713 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：International Journal of Laboratory Hematology

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