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Article: Two patients with α-chain hemoglobin variant Hb Q-Iran detected by measuring hemoglobin A1c using the variant mode of the HA-8180V HPLC analyzer.

Kinoshita, Maki / Shimomura, Daiki / Shimada, Masashi / Kamioka, Mikio / Koga, Masafumi

2024 Volume 15, Issue 2, Page(s) 302–306

Abstract: Hemoglobin variants are often discovered when hemoglobin A1c (HbA1c) levels measured with a high-performance liquid chromatography (HPLC) system in fast mode are found to be low. The HA-8180V HPLC analyzer by Arkray offers two measurement modes: fast ... ...

Abstract	Hemoglobin variants are often discovered when hemoglobin A1c (HbA1c) levels measured with a high-performance liquid chromatography (HPLC) system in fast mode are found to be low. The HA-8180V HPLC analyzer by Arkray offers two measurement modes: fast mode (FM) and variant mode (VM). Two Japanese patients with α-chain variant Hb Q-Iran detected incidentally after analyses with the HA-8180V in VM showed an abnormal peak, are presented. The first patient was a man in his 70 s, and the second patient was a man in his 50 s. Both were non-diabetic, but their results from HbA1c measurement in VM showed an abnormal peak. The VM-HbA1c, FM-HbA1c, and HbA1c measured by enzymatic assay and glycated albumin levels of the two patients were all within the reference ranges. They were diagnosed as having Hb Q-Iran (α2-75Asp → His) by globin gene analysis. It is difficult to detect α-chain hemoglobin variants based on abnormal FM-HbA1c levels, but measuring HbA1c in VM is useful for efficiently detecting hemoglobin variants.
Language	English
Publishing date	2024-01-06
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2574501-3
ISSN	2190-1686 ; 2190-1678
ISSN (online)	2190-1686
ISSN	2190-1678
DOI	10.1007/s13340-023-00682-6
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Article ; Online: New method to differentiate between lupus anticoagulants, progressive coagulation inhibitors and coagulation factor deficiencies in the mixing tests.

Shimomura, Daiki / Kumano, Osamu / Ueda, Kaori / Kitano, Keisuke / Arai, Nobuo / Shimada, Masashi / Kamioka, Mikio

International journal of laboratory hematology

2024

Abstract: Introduction: Mixing tests in activated partial thromboplastin time (APTT) are used for the differentiation between lupus anticoagulants (LA), coagulation inhibitors, and factor deficient samples with APTT prolongation. However, the indexes for the ... ...

Abstract	Introduction: Mixing tests in activated partial thromboplastin time (APTT) are used for the differentiation between lupus anticoagulants (LA), coagulation inhibitors, and factor deficient samples with APTT prolongation. However, the indexes for the differentiation have not been established. The present study aimed to develop new mixing test indexes for the differentiation. Methods: Twenty-six LA-positive, 8 progressive coagulation factor VIII inhibitor, and 35 coagulation deficient samples were employed. APTT were measured for normal plasma, patient plasma, and mixing plasma prepared at a ratio of 1:1 proportion in both without incubation and 2 h-incubation. New two parameters named as ALD50 and mixture plasma-patient plasma after Warming change rate Subtraction (WaS) calculated from the clotting times of normal, 1:1 mixing and patient samples with/without 2 h-incubation were established. In the samples with WaS result of <10.2%, ALD50 of ≥87.8%, and < 87.8% were defined as LA and coagulation factor deficiency, respectively, and WaS of ≥10.2% defined progressive coagulation factor inhibitors. Results: Sensitivity and specificity to LA were 80.8% and 93.0% for ALD50, and sensitivity and specificity to progressive coagulation factor inhibitor were 100.0% and 100.0% for WaS, respectively. The agreement between sample classification and WaS-ALD50 was 88.4% (61/69). Conclusions: ALD50 and WaS showed acceptable sensitivity and specificity to LA and progressive coagulation factor inhibitor, respectively. These indexes would be useful for the differentiation between LA, factor deficiency, and progressive coagulation factor inhibitor in the mixing tests.
Language	English
Publishing date	2024-04-21
Publishing country	England
Document type	Journal Article
ZDB-ID	2268590-X
ISSN	1751-553X ; 1751-5521 ; 0141-9854
ISSN (online)	1751-553X
ISSN	1751-5521 ; 0141-9854
DOI	10.1111/ijlh.14289
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Zs.A 1499: Show issues

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Article ; Online: The First-Derivative Curve of the Coagulation Waveform Reveals the Cause of aPTT Prolongation.

Shimomura, Daiki / Matsumoto, Tomoko / Sugimoto, Kana / Takata, Tokio / Kouno, Aya / Shimada, Masashi / Matsuo, Shuji / Kamioka, Mikio

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis

2020 Volume 26, Page(s) 1076029620978810

Abstract: Clot waveform analysis based on activated partial thromboplastin time (aPTT) is reported to be a useful assay. We attempted to find beneficial parameters with the first-derivative curve. We examined 106 plasma samples with prolonged aPTT and analyzed the ...

Abstract	Clot waveform analysis based on activated partial thromboplastin time (aPTT) is reported to be a useful assay. We attempted to find beneficial parameters with the first-derivative curve. We examined 106 plasma samples with prolonged aPTT and analyzed the first-derivative curve statistically by dividing it into 6 groups (Lupus anticoagulant, Heparin, Direct oral anticoagulants, Factor VIII inhibitor, Hepatic dysfunctions and Factor deficiency). We obtained 7 coordinates for parameter measurement by analyzing the first-derivative curve and set 20 parameters including the velocity axis, the time axis, and area parameters. The distribution was checked by extracting each parameter that showed the most significant difference in the 6 groups. As a result, it was revealed that we could classify aPTT prolongation by using a combination of 3 parameters, the initial-to-peak gradient, the ratio initial-to-intermediate velocity/intermediate-to-peak velocity, and the initial-to-peak area size. We constructed a flowchart combining these 3 parameters and were able to discriminate 75% of the specimens. These parameters derived from the first-derivative curve of clot waveform analysis are useful tools to discriminate aPTT prolongation.
MeSH term(s)	Blood Coagulation Tests/methods ; Humans ; Partial Thromboplastin Time/methods
Language	English
Publishing date	2020-12-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	1237357-6
ISSN	1938-2723 ; 1076-0296
ISSN (online)	1938-2723
ISSN	1076-0296
DOI	10.1177/1076029620978810
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Zs.A 4370: Show issues

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Article: Acute non-heparin-induced thrombocytopenia during hemodiafiltration in a patient with multiple myeloma.

Morita, Makiko / Nakanishi, Kayoko / Masuda, Kenta / Yoshida, Kazuhiro / Shimomura, Daiki / Ishida, Atsumi / Shiga, Shuichi / Ichiyama, Satoshi

Clinical case reports

2019 Volume 7, Issue 4, Page(s) 699–702

Abstract: This report demonstrates that not only heparin-induced thrombocytopenia, but also hemodialysis conditions (platelet activation due to hemodiafiltration and heparin underdosing) may markedly reduce the platelet count and cause clotting in the hemodialysis ...

Abstract	This report demonstrates that not only heparin-induced thrombocytopenia, but also hemodialysis conditions (platelet activation due to hemodiafiltration and heparin underdosing) may markedly reduce the platelet count and cause clotting in the hemodialysis circuit in patients in a hypercoagulable state. The clot prevention effects of bortezomib are therefore of great importance.
Language	English
Publishing date	2019-02-22
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.1997
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Article ; Online: Measuring serum prothrombin in patients treated with warfarin or direct oral anticoagulants.

Kondo, Akira / Kondo, Hirokazu / Nakagawa, Yoshihisa / Kameyama, Hideki / Ito, Hiroyuki / Shimomura, Daiki / Yamanishi, Hachiro / Hatanaka, Noriko / Yamamoto, Yoshikazu / Iwai-Kanai, Eri / Matsuo, Shuji

Clinica chimica acta; international journal of clinical chemistry

2021 Volume 523, Page(s) 224–230

Abstract: Background: Warfarin therapy influences generation of γ-carboxyglutamyl (Gla) residues in prothrombin, causing reduced coagulation activity. It will leave such inactive prothrombin in serum after clot formation, resulting in serum prothrombin ... ...

Abstract	Background: Warfarin therapy influences generation of γ-carboxyglutamyl (Gla) residues in prothrombin, causing reduced coagulation activity. It will leave such inactive prothrombin in serum after clot formation, resulting in serum prothrombin constituting total inactive prothrombin in these patients. Methods: An ELISA was developed to measure biologically inactive prothrombin in serum, and applied to serum from warfarin therapy causing a decrease in Gla residues or direct oral anticoagulant (DOAC) therapy as its contrast. Results: The concentrations of serum prothrombin in both the warfarin and DOAC groups were higher than those in the healthy group (p < 0.01 and p < 0.001, respectively). When serum in the previous three groups was treated with barium carbonate to exclude prothrombin, which lost several Gla residues, the prothrombin concentration in the DOAC group decreased to the same level as that in the healthy group, indicating that prothrombin was obtained at a high level only in the warfarin group (p < 0.01). Conclusions: Warfarin and DOAC led to increase in serum prothrombin concentration. The reason is that DOAC decreases prothrombin recruitment during fibrin clot formation, while warfarin leads to the accumulation of inactive prothrombin, which have a decreased number of Gla residues.
MeSH term(s)	Administration, Oral ; Anticoagulants/therapeutic use ; Atrial Fibrillation/drug therapy ; Blood Coagulation Tests ; Humans ; Prothrombin ; Warfarin/therapeutic use
Chemical Substances	Anticoagulants ; Warfarin (5Q7ZVV76EI) ; Prothrombin (9001-26-7)
Language	English
Publishing date	2021-09-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80228-1
ISSN	1873-3492 ; 0009-8981
ISSN (online)	1873-3492
ISSN	0009-8981
DOI	10.1016/j.cca.2021.09.023
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Article: Influence of Warfarin Therapy on Prothrombin Production and Its Posttranslational Modifications.

Kondo, Akira / Kondo, Hirokazu / Nakagawa, Yoshihisa / Ito, Hiroyuki / Shimomura, Daiki / Hatanaka, Noriko / Yamamoto, Yoshikazu / Nakatani, Misato / Iwai-Kanai, Eri / Matsuo, Shuji

The journal of applied laboratory medicine

2020 Volume 5, Issue 6, Page(s) 1216–1227

Abstract: Background: Protein induced by vitamin K absence-II (PIVKA-II) is produced by the liver during hepatoma and upon warfarin administration. Those patients have disturbed protein synthesis and glycosylation in the liver. This decreases the number of γ- ... ...

Abstract	Background: Protein induced by vitamin K absence-II (PIVKA-II) is produced by the liver during hepatoma and upon warfarin administration. Those patients have disturbed protein synthesis and glycosylation in the liver. This decreases the number of γ-carboxyglutamyl (Gla) residues on prothrombin, converting prothrombin into PIVKA-II. The mechanism of this conversion, however, is not clearly understood. Methods: Prothrombin was isolated from healthy and warfarin-treated individuals whose liver function of protein production was quantitatively normal. Glycan structures in the purified prothrombin containing PIVKA-II were qualitatively analyzed by high performance liquid chromatography after labeling the glycan with fluorophore 2-aminobenzamide. Results: The concentration of PIVKA-II was significantly higher in the warfarin-treated individuals than in the healthy individuals (P< 0.001). Although protein production in the liver was normal in both groups, the concentration of prothrombin was lower in the warfarin-treated individuals than in the healthy individuals (P < 0.001). The main glycan was A2 in the healthy and warfarin-treated individuals (86.6 ± 4.4% and 85.6 ± 3.4%, respectively). Eight types of glycan were characterized in both groups, although generation of PIVKA-II in the warfarin-treated individuals did not lead to variation in glycosylation of prothrombin. Conclusions: Warfarin therapy leads to lower amounts of prothrombin and Gla residues within prothrombin without exerting qualitative and quantitative change in glycan profile and protein synthetic function in the liver.
MeSH term(s)	Biomarkers ; Humans ; Protein Precursors ; Protein Processing, Post-Translational ; Prothrombin/metabolism ; Warfarin
Chemical Substances	Biomarkers ; Protein Precursors ; Warfarin (5Q7ZVV76EI) ; Prothrombin (9001-26-7)
Language	English
Publishing date	2020-06-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2576-9456
ISSN	2576-9456
DOI	10.1093/jalm/jfaa069
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Article: Acute basophilic leukemia associated with the t(16;21)(p11;q22)/

Toda, Yusuke / Nagai, Yuya / Shimomura, Daiki / Kishimori, Chiyuki / Tsuda, Katsuyo / Fukutsuka, Katsuhiro / Hayashida, Masahiko / Ohno, Hitoshi

Clinical case reports

2017 Volume 5, Issue 12, Page(s) 1938–1944

Abstract: We herein report a rare case of acute basophilic leukemia with t(16;21)(p11;q22) generating ... ...

Abstract	We herein report a rare case of acute basophilic leukemia with t(16;21)(p11;q22) generating the
Language	English
Publishing date	2017-10-11
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.1219
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Article ; Online: Delayed Development of Hemolytic Anemia with Fragmented Red Blood Cells and Cardiac and Renal Impairments after High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation for Malignant Lymphoma.

Iioka, Futoshi / Toda, Yusuke / Nagai, Yuya / Akasaka, Takashi / Shimomura, Daiki / Tsuda, Katsuyo / Nakamura, Fumihiko / Ohno, Hitoshi

Acta haematologica

2017 Volume 138, Issue 3, Page(s) 152–161

Abstract: Among 42 consecutive patients with malignant lymphoma who underwent high-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (AHSCT), 5 developed hemolytic anemia with fragmented red blood cells (HA-FrRBCs) on days 87- ... ...

Abstract	Among 42 consecutive patients with malignant lymphoma who underwent high-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (AHSCT), 5 developed hemolytic anemia with fragmented red blood cells (HA-FrRBCs) on days 87-125 (median 107) of AHSCT. Nadir Hb levels ranged between 5.0 and 6.4 g/dL with 2.2-5.6% FrRBCs. All patients developed grade ≥3 hypoxia and heart failure, and 4 developed grade ≥3 hypertension. The ejection fraction of the left ventricle assessed by echocardiography was significantly reduced in 3 patients. Peak creatinine levels were >4 times above the baseline and estimated glomerular filtration rates were reduced to <30 mL/min/1.73 m2. One patient received plasma exchange, while the remaining 4 responded to treatment with diuretics and cardiovascular agents. Hematological parameters normalized within a median duration of 91 days after the development of HA-FrRBCs. Renal and cardiac functions gradually improved, even though renal function did not return to the baseline. HA-FrRBCs associated with cardiac and renal impairments may represent a thrombotic microangiopathy syndrome and are a delayed complication of HDC/AHSCT. The close monitoring of laboratory abnormalities and persistent treatment with cardiovascular agents and diuretics are the mainstay for the management of this condition.
MeSH term(s)	Adult ; Anemia, Hemolytic/etiology ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Creatinine/blood ; Disease-Free Survival ; Echocardiography ; Erythrocytes/cytology ; Erythrocytes/metabolism ; Female ; Heart Ventricles/diagnostic imaging ; Heart Ventricles/physiopathology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hemoglobins/analysis ; Humans ; Lymphoma/mortality ; Lymphoma/pathology ; Lymphoma/therapy ; Male ; Middle Aged ; Renal Insufficiency/etiology ; Transplantation, Autologous ; Treatment Outcome
Chemical Substances	Hemoglobins ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2017
Publishing country	Switzerland
Document type	Case Reports ; Journal Article
ZDB-ID	80008-9
ISSN	1421-9662 ; 0001-5792
ISSN (online)	1421-9662
ISSN	0001-5792
DOI	10.1159/000480288
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Article: Delayed Development of Hemolytic Anemia with Fragmented Red Blood Cells and Cardiac and Renal Impairments after High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation for Malignant Lymphoma

Iioka, Futoshi / Toda, Yusuke / Nagai, Yuya / Akasaka, Takashi / Shimomura, Daiki / Tsuda, Katsuyo / Nakamura, Fumihiko / Ohno, Hitoshi

Acta Haematologica

2017 Volume 138, Issue 3, Page(s) 152–161

Institution	Departments of Hematology and Laboratory Medicine, Tenri Hospital, Tenri, Japan
Abstract	Among 42 consecutive patients with malignant lymphoma who underwent high-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (AHSCT), 5 developed hemolytic anemia with fragmented red blood cells (HA-FrRBCs) on days 87-125 (median 107) of AHSCT. Nadir Hb levels ranged between 5.0 and 6.4 g/dL with 2.2-5.6% FrRBCs. All patients developed grade ≥3 hypoxia and heart failure, and 4 developed grade ≥3 hypertension. The ejection fraction of the left ventricle assessed by echocardiography was significantly reduced in 3 patients. Peak creatinine levels were >4 times above the baseline and estimated glomerular filtration rates were reduced to <30 mL/min/1.73 m2. One patient received plasma exchange, while the remaining 4 responded to treatment with diuretics and cardiovascular agents. Hematological parameters normalized within a median duration of 91 days after the development of HA-FrRBCs. Renal and cardiac functions gradually improved, even though renal function did not return to the baseline. HA-FrRBCs associated with cardiac and renal impairments may represent a thrombotic microangiopathy syndrome and are a delayed complication of HDC/AHSCT. The close monitoring of laboratory abnormalities and persistent treatment with cardiovascular agents and diuretics are the mainstay for the management of this condition.
Keywords	Thrombotic microangiopathy syndrome ; Autologous hematopoietic stem cell transplantation ; Cardiac injury ; Fragmented red blood cells ; High-dose chemotherapy ; Renal injury
Language	English
Publishing date	2017-10-04
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Original Paper
ZDB-ID	80008-9
ISSN	1421-9662 ; 0001-5792
ISSN (online)	1421-9662
ISSN	0001-5792
DOI	10.1159/000480288
Database	Karger publisher's database

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Article ; Online: The Influence of Assay Selection on Prothrombin Time Measured in Patients Treated With Rivaroxaban for Nonvalvular Atrial Fibrillation.

Shimomura, Daiki / Nakagawa, Yoshihisa / Kondo, Hirokazu / Tamura, Toshihiro / Amano, Masashi / Enomoto, Soichiro / Onishi, Naoaki / Tamaki, Yodo / Miyake, Makoto / Kaitani, Kazuaki / Izumi, Chisato / Fukuda, Aya / Nakamura, Fumihiko / Kawano, Seiji

Journal of clinical laboratory analysis

2016 Volume 30, Issue 6, Page(s) 941–946

Abstract: Background: Prothrombin time (PT) can provide a qualitative assessment of the relative intensity of anticoagulation by rivaroxaban. More than ten types of assay are available for the measurement of PT in clinical settings, but it is not yet fully ... ...

Abstract	Background: Prothrombin time (PT) can provide a qualitative assessment of the relative intensity of anticoagulation by rivaroxaban. More than ten types of assay are available for the measurement of PT in clinical settings, but it is not yet fully understood whether their interactions with rivaroxaban are uniform or inconsistent. Methods: We examined 139 blood samples from patients taking rivaroxaban. We measured PT using five different commercially available assays. We also evaluated the estimated rivaroxaban concentration using a chromogenic anti-factor Xa assay. Results: The median estimated concentration of rivaroxaban was 192 ng/ml (interquartile range 85-284 ng/ml). The correlation coefficient (r) between PT and the estimated concentrations of rivaroxaban was as follows: Thromborel S, r = 0.768; Thrombocheck PT, r = 0.861; Coagpia PT-N, r = 0.909; Neoplastin Plus, r = 0.882; and Triniclot PT Excel S, r = 0.870. The gradients of the regression plots differed more than fourfold, and the standard deviation of the regression line ranged from 1.001 to 2.980, which tended to be higher for the assays with the higher regression slope gradients. Conclusion: The estimated concentration of rivaroxaban varied greatly depending on the assay, so the PT measured in patients taking rivaroxaban should be interpreted with caution.
MeSH term(s)	Aged ; Anticoagulants/blood ; Anticoagulants/therapeutic use ; Atrial Fibrillation/drug therapy ; Female ; Humans ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Prothrombin/metabolism ; Retrospective Studies ; Rivaroxaban/blood ; Rivaroxaban/therapeutic use ; Statistics, Nonparametric ; Time Factors
Chemical Substances	Anticoagulants ; Prothrombin (9001-26-7) ; Rivaroxaban (9NDF7JZ4M3)
Language	English
Publishing date	2016-04-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	645095-7
ISSN	1098-2825 ; 0887-8013
ISSN (online)	1098-2825
ISSN	0887-8013
DOI	10.1002/jcla.21960
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