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Article: [Acquired von Willebrand syndrome: a hemostatic disorder frequently encountered in the fields of cardiology and gastroenterology].

Horiuchi, Hisanori

Rinsho ketsueki] The Japanese journal of clinical hematology

2020 Volume 61, Issue 5, Page(s) 542–548

Abstract: von Willebrand disease is a genetic hemostatic disorder that is caused by the qualitative or quantitative dysfunction of the von Willebrand factor (VWF), which is involved in hemostasis. A similar dysfunction sometimes develops without mutations, known ... ...

Abstract	von Willebrand disease is a genetic hemostatic disorder that is caused by the qualitative or quantitative dysfunction of the von Willebrand factor (VWF), which is involved in hemostasis. A similar dysfunction sometimes develops without mutations, known as acquired von Willebrand syndrome (AVWS)
MeSH term(s)	Cardiology ; Gastroenterology ; Hemostatic Disorders ; Humans ; von Willebrand Diseases ; von Willebrand Factor
Chemical Substances	von Willebrand Factor
Language	Japanese
Publishing date	2020-05-28
Publishing country	Japan
Document type	Journal Article
ZDB-ID	390900-1
ISSN	0485-1439
ISSN	0485-1439
DOI	10.11406/rinketsu.61.542
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Article: [A hemostatic disorder caused by high shear stress: acquired von Willebrand syndrome].

Horiuchi, Hisanori

Rinsho ketsueki] The Japanese journal of clinical hematology

2018 Volume 59, Issue 10, Page(s) 2233–2237

Abstract: The von Willebrand factors (VWFs) play critical role in hemostasis and thrombosis formation. VWFs are produced in and secreted as large multimers from endothelial cells, and shear stress-dependently cleaved into 2-80 multimers by their specific protease, ...

Abstract	The von Willebrand factors (VWFs) play critical role in hemostasis and thrombosis formation. VWFs are produced in and secreted as large multimers from endothelial cells, and shear stress-dependently cleaved into 2-80 multimers by their specific protease, ADATS13. Because high molecular weight VWFs play important roles in platelet aggregation, the loss of high molecular weight VWFs caused by pathological high-shear stress induces a hemostatic disorder known as acquired von Willebrand syndrome (AVWS) type IIA. The most well-known cause of this loss is aortic stenosis, which is accompanied by gastrointestinal bleeding most often as a result of angiodysplasia; this comprises a condition known as Heyde's syndrome. Additionally, various cardiovascular diseases that generate excessive high-shear stress in the blood stream, such as hypertrophic obstructive cardiomyopathy (HOCM), mitral regurgitation, pulmonary hypertension, and some congenital heart diseases, and mechanical circulatory support systems, such as left ventricular assist device (LVAD), cause AVWS.
MeSH term(s)	Angiodysplasia/pathology ; Aortic Valve Stenosis/pathology ; Hemostasis ; Hemostatic Disorders/diagnosis ; Hemostatic Disorders/pathology ; Humans ; von Willebrand Diseases/diagnosis ; von Willebrand Diseases/pathology ; von Willebrand Factor
Chemical Substances	von Willebrand Factor
Language	Japanese
Publishing date	2018-10-10
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	390900-1
ISSN	0485-1439
ISSN	0485-1439
DOI	10.11406/rinketsu.59.2233
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Article ; Online: Platelet αIIbβ3 integrin binds to SARS-CoV-2 spike protein of alpha strain but not wild type and omicron strains.

Ito, Koyu / Goto, Kota / Shirakawa, Ryutaro / Horiuchi, Hisanori / Ogasawara, Kouetsu

Biochemical and biophysical research communications

2023 Volume 657, Page(s) 80–85

Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 causes a pandemic infectious disease, Coronavirus disease 2019 (COVID-19). It causes respiratory infection. Then, it progresses into a systemic infection by involving other organs. This ... ...

Abstract	Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 causes a pandemic infectious disease, Coronavirus disease 2019 (COVID-19). It causes respiratory infection. Then, it progresses into a systemic infection by involving other organs. This progression mechanism remains to be elucidated, although thrombus formation plays an important role in its progression. Platelets is involved in the thrombus formation by aggregating each other through association of activated αIIbβ3 integrin with the Arg-Gly-Asp (RGD) motif-containing its ligands such as fibrinogen and von Willebrand factor. SARS-CoV-2 enters host cells through association of the spike protein (S-protein) with its receptor, angiotensin-converting enzyme 2 (ACE-2), on the host cells. While presence of ACE2 in platelets is suspicious, S-protein harbors the RGD sequences within its receptor binding domain. Therefore, it could be possible SARS-CoV-2 enter platelets through association of S-protein with αIIbβ3. In this study, we found that receptor binding domain of S-protein of WT SARS-CoV-2 strain barely bound to isolated healthy human platelets. In contrast, highly toxic alpha-strain-based N501Y substitution strongly bound to platelets in a RGD dependent manner, although binding of S protein did not induce platelet aggregation or activation. This binding may serve for transferring the infection to systemic organs.
MeSH term(s)	Humans ; Spike Glycoprotein, Coronavirus/chemistry ; COVID-19 ; SARS-CoV-2/metabolism ; Platelet Glycoprotein GPIIb-IIIa Complex/metabolism ; Protein Binding ; Oligopeptides/metabolism ; Thrombosis
Chemical Substances	spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Platelet Glycoprotein GPIIb-IIIa Complex ; Oligopeptides
Language	English
Publishing date	2023-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.03.057
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Article ; Online: Platelet αIIbβ3 integrin binds to SARS-CoV-2 spike protein of alpha strain but not wild type and omicron strains

Ito, Koyu / Goto, Kota / Shirakawa, Ryutaro / Horiuchi, Hisanori / Ogasawara, Kouetsu

Biochemical and Biophysical Research Communications. 2023 May, v. 657 p.80-85

2023

Abstract	Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 causes a pandemic infectious disease, Coronavirus disease 2019 (COVID-19). It causes respiratory infection. Then, it progresses into a systemic infection by involving other organs. This progression mechanism remains to be elucidated, although thrombus formation plays an important role in its progression. Platelets is involved in the thrombus formation by aggregating each other through association of activated αIIbβ3 integrin with the Arg-Gly-Asp (RGD) motif-containing its ligands such as fibrinogen and von Willebrand factor. SARS-CoV-2 enters host cells through association of the spike protein (S-protein) with its receptor, angiotensin-converting enzyme 2 (ACE-2), on the host cells. While presence of ACE2 in platelets is suspicious, S-protein harbors the RGD sequences within its receptor binding domain. Therefore, it could be possible SARS-CoV-2 enter platelets through association of S-protein with αIIbβ3. In this study, we found that receptor binding domain of S-protein of WT SARS-CoV-2 strain barely bound to isolated healthy human platelets. In contrast, highly toxic alpha-strain-based N501Y substitution strongly bound to platelets in a RGD dependent manner, although binding of S protein did not induce platelet aggregation or activation. This binding may serve for transferring the infection to systemic organs.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus ; Severe acute respiratory syndrome coronavirus 2 ; blood coagulation factors ; fibrinogen ; humans ; integrins ; ligands ; pandemic ; peptidyl-dipeptidase A ; platelet aggregation ; research ; respiratory tract diseases ; thrombosis ; toxicity ; SARS-CoV-2 ; Platelet ; αIIbβ3 integrin
Language	English
Dates of publication	2023-05
Size	p. 80-85.
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.03.057
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Time of Day of Vaccination Does Not Associate With SARS-CoV-2 Antibody Titer Following First Dose of mRNA COVID-19 Vaccine.

Yamanaka, Yujiro / Yokota, Isao / Yasumoto, Atsushi / Morishita, Eriko / Horiuchi, Hisanori

Journal of biological rhythms

2022 Volume 37, Issue 6, Page(s) 700–706

Abstract: The immune system exhibits circadian rhythms, and its response to viral infection is influenced by the circadian clock system. Previous studies have reported associations between the time of day of vaccination against COVID-19 and production of anti-SARS- ...

Abstract	The immune system exhibits circadian rhythms, and its response to viral infection is influenced by the circadian clock system. Previous studies have reported associations between the time of day of vaccination against COVID-19 and production of anti-SARS-CoV-2 antibody titer. We examined the effect of vaccination time of day on anti-SARS-CoV-2 antibody titer after the first dose of vaccination with the mRNA-1273 (Moderna) COVID-19 vaccine in an adult population. A total of 332 Japanese adults participated in the present study. All participants were not infected with SARS-CoV-2 and had already received the first dose of mRNA-1273 2 to 4 weeks prior to participating in the study. The participants were asked to provide basic demographic characteristics (age, sex, medical history, allergy, medication, and mean sleep duration), the number of days after the first dose of vaccination, and the time of day of vaccination. Blood was collected from the participants, and SARS-CoV-2 antibody titers were measured. Ordinary least square regression was used for assessing the relationship between basic demographic characteristics, number of days after vaccination, time of day of vaccination, and the log
MeSH term(s)	Adult ; Humans ; COVID-19 Vaccines ; RNA, Messenger ; COVID-19/prevention & control ; SARS-CoV-2 ; Circadian Rhythm ; Vaccination ; 2019-nCoV Vaccine mRNA-1273
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger ; 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4)
Language	English
Publishing date	2022-09-26
Publishing country	United States
Document type	Letter
ZDB-ID	896387-3
ISSN	1552-4531 ; 0748-7304
ISSN (online)	1552-4531
ISSN	0748-7304
DOI	10.1177/07487304221124661
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Article ; Online: COVID-19-Related Thrombosis in Japan: Final Report of a Questionnaire-Based Survey in 2020.

Horiuchi, Hisanori / Morishita, Eriko / Urano, Tetsumei / Yokoyama, Kenji

Journal of atherosclerosis and thrombosis

2021 Volume 28, Issue 4, Page(s) 406–416

Abstract: A questionnaire on COVID-19-related thrombosis in patients hospitalized before Aug 31, 2020, was sent to 399 hospitals throughout Japan. Responses were received from 111 (27.8%) with information on 6,202 COVID-19 patients. Of these, 333 and 56 required ... ...

Abstract	A questionnaire on COVID-19-related thrombosis in patients hospitalized before Aug 31, 2020, was sent to 399 hospitals throughout Japan. Responses were received from 111 (27.8%) with information on 6,202 COVID-19 patients. Of these, 333 and 56 required ventilation or extracorporeal membrane oxygenation (ECMO), respectively, and 212 died (3.4%). D-dimer levels were measured in 75.0% of the patients, revealing that 9.2% and 7.6% exhibited D-dimer increases of 3-8-fold and ≥8-fold the reference value, respectively. Thrombotic events occurred in 108 patients (1.86% of the 5,807 patients with available data) including symptomatic cerebral infarction in 24, myocardial infarction in 7, deep vein thrombosis in 41, pulmonary thromboembolism in 30, and other thrombotic events in 22. Some patients developed multiple thrombotic events. Thrombosis occurred in 32 patients with mild or moderate COVID-19 severity (0.59% of those with data available) and in 52 patients on ventilation or ECMO (13.5% of severe patients for whom data were available). Thrombosis occurred in 67 patients during worsening clinical condition and in 26 during recovery. Anticoagulant therapy was provided to 893 patients (14.6% of the 6,119 patients with available data), the main reasons being provided as elevated D-dimer levels and worsening clinical condition.
MeSH term(s)	Aged ; Anticoagulants/therapeutic use ; COVID-19/complications ; COVID-19/epidemiology ; Extracorporeal Membrane Oxygenation ; Female ; Fibrin Fibrinogen Degradation Products/analysis ; Hospitalization ; Humans ; Incidence ; Japan/epidemiology ; Male ; Middle Aged ; Myocardial Infarction ; Oxygen/metabolism ; Respiration, Artificial ; Surveys and Questionnaires ; Thrombosis/complications ; Thrombosis/epidemiology
Chemical Substances	Anticoagulants ; Fibrin Fibrinogen Degradation Products ; fibrin fragment D ; Oxygen (S88TT14065)
Language	English
Publishing date	2021-03-06
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2011474-6
ISSN	1880-3873 ; 1340-3478
ISSN (online)	1880-3873
ISSN	1340-3478
DOI	10.5551/jat.RPT001
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Article ; Online: Proton-pump inhibitors could be innocent when used concomitantly with clopidogrel.

Horiuchi, Hisanori

Circulation journal : official journal of the Japanese Circulation Society

2012 Volume 76, Issue 11, Page(s) 2542–2543

MeSH term(s)	Acute Coronary Syndrome/drug therapy ; Anti-Ulcer Agents/administration & dosage ; Aspirin/administration & dosage ; Blood Platelets/metabolism ; Clopidogrel ; Famotidine/administration & dosage ; Female ; Humans ; Male ; Omeprazole/administration & dosage ; Platelet Aggregation Inhibitors/administration & dosage ; Ticlopidine/administration & dosage ; Ticlopidine/analogs & derivatives
Chemical Substances	Anti-Ulcer Agents ; Platelet Aggregation Inhibitors ; Famotidine (5QZO15J2Z8) ; Clopidogrel (A74586SNO7) ; Omeprazole (KG60484QX9) ; Ticlopidine (OM90ZUW7M1) ; Aspirin (R16CO5Y76E)
Language	English
Publishing date	2012-09-19
Publishing country	Japan
Document type	Editorial ; Comment
ZDB-ID	2068090-9
ISSN	1347-4820 ; 1346-9843
ISSN (online)	1347-4820
ISSN	1346-9843
DOI	10.1253/circj.cj-12-1117
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Article ; Online: COVID-19 and Thrombosis: Clinical Aspects.

Urano, Tetsumei / Yasumoto, Atsushi / Yokoyama, Kenji / Horiuchi, Hisanori / Morishita, Eriko / Suzuki, Yuko

Current drug targets

2022 Volume 23, Issue 17, Page(s) 1567–1572

Abstract: In coronavirus disease 2019 (COVID-19), thrombus formation is related to the pathogenesis of acute respiratory distress syndrome (ARDS) and the progression of clinical symptoms. Severe damage to vascular endothelial cells and the associated cytokine ... ...

Abstract	In coronavirus disease 2019 (COVID-19), thrombus formation is related to the pathogenesis of acute respiratory distress syndrome (ARDS) and the progression of clinical symptoms. Severe damage to vascular endothelial cells and the associated cytokine storm after SARS-CoV-2 infection cause thrombogenesis and contribute to the development of more severe and unique thromboses compared to other infectious diseases. Thromboses occur more often in critically ill patients. In addition to pulmonary thromboembolism (PE) and deep vein thrombosis, acute myocardial infarction, peripheral arterial thrombosis, and aortic thrombosis have also been reported. In PE, thrombi develop in both pulmonary arteries and alveolar capillaries. These, together with intraalveolar fibrin deposition, interfere with effective gaseous exchange in the lungs and exacerbate the clinical symptoms of ARDS in patients with COVID-19. Pharmacological thromboprophylaxis is recommended for all hospitalized patients to prevent both thrombosis and aggravation of ARDS, and other organ failures. Although the pediatric population is mostly asymptomatic or develops mild disease after SARS-CoV-2 infection, a new inflammatory disorder affecting the cardiovascular system, multisystem inflammatory syndrome in children (MIS-C), has been reported. Similar to Kawasaki disease, acute myocarditis, coronary vasculitis, and aneurysms are typically seen in MISC, although these two are now considered distinct entities. A similar acute myocarditis is also observed in young male adults, in which a hyperinflammatory state after SARS-CoV-2 infection seems to be involved. Several side effects following vaccination against COVID-19 have been reported, including vaccine-induced immune thrombotic thrombocytopenia and acute myocarditis. Although these could be serious and life-threatening, the cases are very rare, thus, the benefits of immunization still outweigh the risks.
MeSH term(s)	Child ; Humans ; Male ; COVID-19/complications ; Endothelial Cells ; Anticoagulants ; SARS-CoV-2 ; Venous Thromboembolism
Chemical Substances	Anticoagulants
Language	English
Publishing date	2022-10-06
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2064859-5
ISSN	1873-5592 ; 1389-4501
ISSN (online)	1873-5592
ISSN	1389-4501
DOI	10.2174/1389450123666221005092350
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Article: Impact of intraoperative use of venovenous extracorporeal membrane oxygenation on the status of von Willebrand factor large multimers during single lung transplantation.

Oishi, Hisashi / Okada, Yoshinori / Suzuki, Yamato / Hirama, Takashi / Ejima, Yutaka / Fujimaki, Shin-Ichi / Sugawara, Shingo / Okubo, Noriyuki / Horiuchi, Hisanori

Journal of thoracic disease

2023 Volume 15, Issue 8, Page(s) 4262–4272

Abstract: Background: von Willebrand factors (vWFs), hemostatic factors, are produced as large multimers and are shear stress-dependently cleaved to become the appropriate size. A reduction in vWF large multimers develops in various conditions including the use ... ...

Abstract	Background: von Willebrand factors (vWFs), hemostatic factors, are produced as large multimers and are shear stress-dependently cleaved to become the appropriate size. A reduction in vWF large multimers develops in various conditions including the use of extracorporeal life support, which can cause excessive-high shear stress in the blood flow and result in hemostatic disorders. The objective of this prospective study was to investigate the impact of venovenous extracorporeal membrane oxygenation (VV ECMO) use on the status of vWF large multimers and hemostatic disorders during single lung transplantation (SLT). Methods: We prospectively enrolled 12 patients who underwent SLT at our center. Among them, seven patients were supported by VV ECMO intraoperatively (ECMO group) and the remaining five patients underwent SLT without ECMO support (control group). The vWF large multimer index (%) was defined as the ratio of the large multimer proportion in total vWF (vWF large multimer ratio) derived from a patient's plasma to that from standard human plasma. Results: The vWF large multimer index at the end of the surgery was significantly lower in the ECMO group than in the control group (112.6% Conclusions: During SLT, the use of VV ECMO caused a decrease in the vWF large multimer index. The short duration of time of VV ECMO use in our study did not significantly affect the intra- and postoperative outcomes including blood loss, blood transfusion, and re-exploration thoracotomy for bleeding. Nevertheless, to comprehensively evaluate the actual influence of this decrease in the vWF large multimer index on intra- and postoperative outcomes, a multicenter larger-scale study is warranted.
Language	English
Publishing date	2023-07-28
Publishing country	China
Document type	Journal Article
ZDB-ID	2573571-8
ISSN	2077-6624 ; 2072-1439
ISSN (online)	2077-6624
ISSN	2072-1439
DOI	10.21037/jtd-23-275
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Article ; Online: Individual Variability in von Willebrand Factor Fragility in Response to Shear Stress: A Possible Clue for Predicting Bleeding Risk.

Sakatsume, Ko / Akiyama, Masatoshi / Sakota, Daisuke / Hijikata, Wataru / Horiuchi, Hisanori / Maruyama, Osamu / Saiki, Yoshikatsu

ASAIO journal (American Society for Artificial Internal Organs : 1992)

2021 Volume 68, Issue 9, Page(s) 1128–1134

Abstract: Acquired von Willebrand syndrome (AVWS), characterized by reduced von Willebrand factor (VWF) large multimers, has recently been implicated as the principal mechanism underlying bleeding in patients implanted with left ventricular assist devices (LVADs). ...

Abstract	Acquired von Willebrand syndrome (AVWS), characterized by reduced von Willebrand factor (VWF) large multimers, has recently been implicated as the principal mechanism underlying bleeding in patients implanted with left ventricular assist devices (LVADs). Hematological severity of AVWS varies among patients, even if an identical device is implanted. We investigated whether this diversity in hematological severity is due to individual variability in VWF fragility, according to responses to incremental shear stress. Whole-blood samples were sheared at 20,000-40,000 s -1 shear rate, an index of shear stress, using a custom-made shear stressor that could generate shear stress compatible with that produced by an LVAD. The degree of VWF large multimers degradation was evaluated using the VWF large multimer index. A significant inverse correlation was observed between the VWF large multimer index and LVAD-compatible magnitudes of shear stress: the VWF large multimer indices were 68.5 ± 18.3, 48.0 ± 13.9, 33.9 ± 12.1, 23.7 ± 7.9, and 18.7% ± 8.7% at 20,000, 25,000, 30,000, 35,000, and 40,000 s -1 of shear rates, respectively ( P < 0.0001). Furthermore, experimental VWF large multimer index values were compatible with those derived from patients with implanted LVADs (median; 28.9%). Finally, reduction in the VWF large multimer index corresponding to shear stress showed individual variation. We demonstrated that the combined use of a novel high shear stress loading device and quantitative evaluation of VWF large multimers may predict risk of bleeding before LVAD implantation.
MeSH term(s)	Heart-Assist Devices/adverse effects ; Hemorrhage/etiology ; Humans ; Stress, Mechanical ; von Willebrand Diseases/etiology ; von Willebrand Factor/metabolism
Chemical Substances	von Willebrand Factor
Language	English
Publishing date	2021-12-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	759982-1
ISSN	1538-943X ; 0162-1432 ; 1058-2916
ISSN (online)	1538-943X
ISSN	0162-1432 ; 1058-2916
DOI	10.1097/MAT.0000000000001623
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