{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T08:24:04Z","timestamp":1777969444935,"version":"3.51.4"},"reference-count":43,"publisher":"Georg Thieme Verlag KG","issue":"06","funder":[{"name":"MEXT\/JSTH Kakenhi","award":["19H03661"],"award-info":[{"award-number":["19H03661"]}]},{"DOI":"10.13039\/100009665","name":"Vehicle Racing Commemorative Foundation","doi-asserted-by":"crossref","award":["6236"],"award-info":[{"award-number":["6236"]}],"id":[{"id":"10.13039\/100009665","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008884","name":"Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100008884","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["A368TS"],"award-info":[{"award-number":["A368TS"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The role of erythrocytes in platelet adhesion to von Willebrand factor (VWF) on the vessel wall through their membrane glycoprotein (GP)Ib\u03b1 under blood flow conditions has not yet been elucidated. Blood specimens containing fluorescent-labeled platelets and native, biochemically fixed, or artificial erythrocytes at various hematocrits were perfused on the surface of VWF immobilized on the wall at a shear rate of 1,500\u2009s\u22121. The rates of platelet adhesion were measured under each condition. The computer simulation of platelet adhesion to the VWF on the wall at the same shear rate was conducted by solving the governing equations with a finite-difference method on a K computer. The rates of platelet adhesion were calculated at various hematocrit conditions in the computational domain of 100\u2009\u00b5m (x-axis)\u2009\u00d7\u2009400\u2009\u00b5m (y-axis)\u2009\u00d7\u2009100\u2009\u00b5m (z-axis). Biological experiments demonstrated a positive correlation between the rates of platelet adhesion and hematocrit values in native, fixed, and artificial erythrocytes. (r\u2009=\u20090.992, 0.934, and 0.825 respectively, p\u2009&lt;\u20090.05 for all). The computer simulation results supported the hematocrit-dependent increase in platelet adhesion rates on VWF (94.3\/second at 10%, 185.2\/second at 20%, and 327.9\/second at 30%). These results suggest that erythrocytes play an important role in platelet adhesion to VWF. The augmented z-axis fluctuation of flowing platelets caused by the physical presence of erythrocytes is speculated to be the cause of the hematocrit-dependent increase in platelet adhesion.<\/jats:p>","DOI":"10.1055\/a-1677-9499","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T23:04:00Z","timestamp":1635203040000},"page":"974-983","source":"Crossref","is-referenced-by-count":9,"title":["Important Regulatory Roles of Erythrocytes in Platelet Adhesion to the von Willebrand Factor on the Wall under Blood Flow Conditions"],"prefix":"10.1055","volume":"122","author":[{"given":"Noriko","family":"Tamura","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology), Research Center for Metabolic Disease, Tokai University School of Medicine and Tokai University Graduate School of Medicine, Isehara, Japan"},{"name":"Department of Health and Nutrition, Niigata University of Health and Welfare, Niigata, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Bio-engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Shiozaki","sequence":"additional","affiliation":[{"name":"Department of Bio-engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyasu","family":"Sugiyama","sequence":"additional","affiliation":[{"name":"Department of Mechanical Science and Bioengineering, Osaka University School of Engineering Science, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masamitsu","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology), Research Center for Metabolic Disease, Tokai University School of Medicine and Tokai University Graduate School of Medicine, Isehara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology), Research Center for Metabolic Disease, Tokai University School of Medicine and Tokai University Graduate School of Medicine, Isehara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Takagi","sequence":"additional","affiliation":[{"name":"Department of Bio-engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6821-1504","authenticated-orcid":false,"given":"Shinya","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Medicine (Cardiology), Research Center for Metabolic Disease, Tokai University School of Medicine and Tokai University Graduate School of Medicine, Isehara, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2021,12,29]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.thromres.2017.07.018","article-title":"The role of von Willebrand factor in primary haemostasis under conditions of haemodilution","volume":"157","author":"I Jalaer","year":"2017","journal-title":"Thromb Res"},{"issue":"02","key":"ref2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0092-8674(00)80983-6","article-title":"Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor","volume":"84","author":"B Savage","year":"1996","journal-title":"Cell"},{"issue":"05","key":"ref3","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S0092-8674(00)81607-4","article-title":"Specific synergy of multiple substrate-receptor interactions in platelet thrombus formation under flow","volume":"94","author":"B Savage","year":"1998","journal-title":"Cell"},{"issue":"02","key":"ref4","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1161\/01.CIR.0000021427.87256.7E","article-title":"Involvement of glycoprotein VI in platelet thrombus formation on both collagen and von Willebrand factor surfaces under flow conditions","volume":"106","author":"S Goto","year":"2002","journal-title":"Circulation"},{"issue":"21","key":"ref5","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1161\/01.CIR.0000016703.93845.AF","article-title":"Functional significance of adenosine 5\u2032-diphosphate receptor (P2Y(12)) in platelet activation initiated by binding of von Willebrand factor to platelet GP Ibalpha induced by conditions of high shear rate","volume":"105","author":"S Goto","year":"2002","journal-title":"Circulation"},{"issue":"02","key":"ref6","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1172\/JCI973","article-title":"Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions","volume":"101","author":"S Goto","year":"1998","journal-title":"J Clin Invest"},{"issue":"06","key":"ref7","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1016\/j.bpj.2019.01.040","article-title":"In vitro measurement and modeling of platelet adhesion on VWF-coated surfaces in channel flow","volume":"116","author":"Q M Qi","year":"2019","journal-title":"Biophys J"},{"issue":"06","key":"ref8","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1172\/JCI112736","article-title":"Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation","volume":"78","author":"J L Moake","year":"1986","journal-title":"J Clin Invest"},{"issue":"04","key":"ref9","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1172\/JCI115124","article-title":"The role of von Willebrand factor and fibrinogen in platelet aggregation under varying shear stress","volume":"87","author":"Y Ikeda","year":"1991","journal-title":"J Clin Invest"},{"issue":"06","key":"ref10","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1161\/01.CIR.86.6.1859","article-title":"Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation","volume":"86","author":"S Goto","year":"1992","journal-title":"Circulation"},{"issue":"01","key":"ref11","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1182\/blood.V62.1.214.214","article-title":"Red blood cell size is important for adherence of blood platelets to artery subendothelium","volume":"62","author":"P A Aarts","year":"1983","journal-title":"Blood"},{"issue":"11","key":"ref12","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1182\/blood.V75.11.2185.2185","article-title":"Effects of red blood cell concentration on hemostasis and thrombus formation in a primate model","volume":"75","author":"Y Cadroy","year":"1990","journal-title":"Blood"},{"issue":"03","key":"ref13","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/0026-2862(75)90070-9","article-title":"Platelet interaction with subendothelium in a perfusion system: physical role of red blood cells","volume":"9","author":"V T Turitto","year":"1975","journal-title":"Microvasc Res"},{"issue":"01","key":"ref14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ypmed.2009.04.015","article-title":"Hematocrit and the risk of coronary heart disease mortality in the TAMRISK study, a 28-year follow-up","volume":"49","author":"T Kunnas","year":"2009","journal-title":"Prev Med"},{"issue":"04","key":"ref15","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/0002-8703(81)90136-8","article-title":"Hematocrit and risk of coronary heart disease: the Puerto Rico Health Program","volume":"101","author":"P D Sorlie","year":"1981","journal-title":"Am Heart J"},{"issue":"09","key":"ref16","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1253\/circj.CJ-14-1434","article-title":"Platelets: small in size but essential in the regulation of vascular homeostasis - translation from basic science to clinical medicine","volume":"79","author":"S Goto","year":"2015","journal-title":"Circ J"},{"issue":"01","key":"ref17","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jacc.2005.08.055","article-title":"Dependence of platelet thrombus stability on sustained glycoprotein IIb\/IIIa activation through adenosine 5\u2032-diphosphate receptor stimulation and cyclic calcium signaling","volume":"47","author":"S Goto","year":"2006","journal-title":"J Am Coll Cardiol"},{"issue":"04","key":"ref18","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1172\/JCI112667","article-title":"Divalent cation regulation of the surface orientation of platelet membrane glycoprotein IIb. Correlation with fibrinogen binding function and definition of a novel variant of Glanzmann's thrombasthenia","volume":"78","author":"M H Ginsberg","year":"1986","journal-title":"J Clin Invest"},{"issue":"03","key":"ref19","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1253\/circj.CJ-08-0465","article-title":"Important regulatory role of activated platelet-derived procoagulant activity in the propagation of thrombi formed under arterial blood flow conditions","volume":"73","author":"N Tamura","year":"2009","journal-title":"Circ J"},{"issue":"01","key":"ref20","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/j.1538-7836.2005.01701.x","article-title":"Co-localization of von Willebrand factor with platelet thrombi, tissue factor and platelets with fibrin, and consistent presence of inflammatory cells in coronary thrombi obtained by an aspiration device from patients with acute myocardial infarction","volume":"4","author":"Y Hoshiba","year":"2006","journal-title":"J Thromb Haemost"},{"issue":"05","key":"ref21","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1161\/01.CIR.99.5.608","article-title":"Enhanced shear-induced platelet aggregation in acute myocardial infarction","volume":"99","author":"S Goto","year":"1999","journal-title":"Circulation"},{"issue":"02","key":"ref22","first-page":"204","article-title":"Plasma concentration of von Willebrand factor in acute myocardial infarction","volume":"84","author":"H Sakai","year":"2000","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref23","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1161\/01.ATV.16.5.611","article-title":"Platelet adhesion to multimeric and dimeric von Willebrand factor and to collagen type III preincubated with von Willebrand factor","volume":"16","author":"Y P Wu","year":"1996","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1299\/jbse.7.72","article-title":"A computational blood flow analysis in a capillary vessel including multiple red blood cells and platelets","volume":"7","author":"S Ii","year":"2012","journal-title":"J Biomech Sci Engineer"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.piutam.2014.01.018","article-title":"Toward the multi-scale simulation for a human body using the Next-generation Supercomputer","volume":"10","author":"Y Matsumoto","year":"2014","journal-title":"Procedia IUTAM"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1299\/jbse.7.275","article-title":"ISHIKAWA KL, TAKAGI S. Numerical study on platelet adhesion to vessel walls using the kinetic Monte Carlo method","volume":"7","author":"SHIOZAKI S","year":"2012","journal-title":"J Biomech Sci Engineer"},{"issue":"02","key":"ref27","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1152\/advan.00009.2013","article-title":"Using a classic paper by Robin Fahraeus and Torsten Lindqvist to teach basic hemorheology","volume":"37","author":"L N Toksvang","year":"2013","journal-title":"Adv Physiol Educ"},{"key":"ref28","first-page":"H1239","article-title":"Near-wall excess of platelets induced by lateral migration of erythrocytes in flowing blood","volume":"264","author":"W S Uijttewaal","year":"1993","journal-title":"Am J Physiol"},{"issue":"02","key":"ref29","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3233\/BIR-1989-26202","article-title":"Stanley Mason: his contribution to the science of biorheology","volume":"26","author":"H L Goldsmith","year":"1989","journal-title":"Biorheology"},{"issue":"09","key":"ref30","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1093\/emboj\/20.9.2120","article-title":"Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen","volume":"20","author":"B Nieswandt","year":"2001","journal-title":"EMBO J"},{"issue":"S 01","key":"ref31","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1016\/j.thromres.2007.03.011","article-title":"The role of von Willebrand factor in thrombus formation","volume":"120","author":"Z M Ruggeri","year":"2007","journal-title":"Thromb Res"},{"issue":"11","key":"ref32","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1038\/nm1102-1227","article-title":"Platelets in atherothrombosis","volume":"8","author":"Z M Ruggeri","year":"2002","journal-title":"Nat Med"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"057301","DOI":"10.1103\/PhysRevE.71.057301","article-title":"Reexamination of Hagen-Poiseuille flow: shape dependence of the hydraulic resistance in microchannels","volume":"71","author":"N A Mortensen","year":"2005","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys"},{"issue":"04","key":"ref34","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1159\/000008588","article-title":"Use of the Hagen-Poiseuille law: a new mathematical approach for the integration and evaluation of anorectal physiological testing in patients with faecal incontinence and pelvic dyschezia and in normal controls","volume":"30","author":"A Farag","year":"1998","journal-title":"Eur Surg Res"},{"key":"ref35","first-page":"311","article-title":"Axial accumulation of red cells: probable causes and effects of interest in artificial organs","volume":"10","author":"R V Repetti","year":"1964","journal-title":"Trans Am Soc Artif Intern Organs"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1299\/jfst.5.475","article-title":"Full-Eulerian finite-difference simulation of fluid flow in hyperelastic wavy channel","volume":"5","author":"N Nagano","year":"2010","journal-title":"J Fluid Sci Technol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.jcp.2010.09.032","article-title":"A full Eulerian finite difference approach for solving fluid\u2013structure coupling problems","volume":"230","author":"K Sugiyama","year":"2011","journal-title":"J Comput Phys"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.thromres.2019.05.007","article-title":"Potential different impact of inhibition of thrombin function and thrombin generation rate for the growth of thrombi formed at site of endothelial injury under blood flow condition","volume":"179","author":"K Ayabe","year":"2019","journal-title":"Thromb Res"},{"issue":"02","key":"ref39","doi-asserted-by":"crossref","first-page":"201","DOI":"10.5551\/jat.26203","article-title":"Development of virtual platelets implementing the functions of three platelet membrane proteins with different adhesive characteristics","volume":"22","author":"A Tomita","year":"2015","journal-title":"J Atheroscler Thromb"},{"issue":"02","key":"ref40","first-page":"710","article-title":"In vivo imaging in mice reveals local cell dynamics and inflammation in obese adipose tissue","volume":"118","author":"S Nishimura","year":"2008","journal-title":"J Clin Invest"},{"issue":"04","key":"ref41","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1111\/j.1538-7836.2009.03284.x","article-title":"Platelet adhesion to multimerin 1 in vitro: influences of platelet membrane receptors, von Willebrand factor and shear","volume":"7","author":"S Tasneem","year":"2009","journal-title":"J Thromb Haemost"},{"issue":"03","key":"ref42","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1182\/blood.V94.3.968.415a13_968_975","article-title":"Real-time analysis of mural thrombus formation in various platelet aggregation disorders: distinct shear-dependent roles of platelet receptors and adhesive proteins under flow","volume":"94","author":"S Tsuji","year":"1999","journal-title":"Blood"},{"issue":"07","key":"ref43","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1039\/c2lc21145a","article-title":"Microfluidic system for simultaneous optical measurement of platelet aggregation at multiple shear rates in whole blood","volume":"12","author":"M Li","year":"2012","journal-title":"Lab Chip"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1677-9499.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T14:49:17Z","timestamp":1660142957000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1677-9499"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,25]]},"references-count":43,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2022,7,4]]},"published-print":{"date-parts":[[2022,6]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1677-9499","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10,25]]},"published":{"date-parts":[[2021,10,25]]}}}