{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T21:51:05Z","timestamp":1774907465371,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["PI10\/01222"],"award-info":[{"award-number":["PI10\/01222"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["EU-FEDER"],"award-info":[{"award-number":["EU-FEDER"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["CTS-554"],"award-info":[{"award-number":["CTS-554"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Consejer\u00eda de Universidad, Investigaci\u00f3n e Innovaci\u00f3n, Junta de Andaluc\u00eda","award":["PI10\/01222"],"award-info":[{"award-number":["PI10\/01222"]}]},{"name":"Consejer\u00eda de Universidad, Investigaci\u00f3n e Innovaci\u00f3n, Junta de Andaluc\u00eda","award":["EU-FEDER"],"award-info":[{"award-number":["EU-FEDER"]}]},{"name":"Consejer\u00eda de Universidad, Investigaci\u00f3n e Innovaci\u00f3n, Junta de Andaluc\u00eda","award":["CTS-554"],"award-info":[{"award-number":["CTS-554"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polyphosphate (polyP), a phosphate polymer released by activated platelets, may modulate various stages of hemostasis by binding to blood proteins. In this context, we previously reported that polyP binds to the von Willebrand factor (VWF). One of the most significant functions of VWF is to bind to and protect the blood circulating Factor VIII (FVIII). Therefore, here, we study the role of polyP in the VWF\u2013FVIII complex in vitro and suggest its biological significance. Surface plasmon resonance and electrophoretic mobility assays indicated that polyP binds dynamically to VWF only in the absence of FVIII. Using the VWF Ristocetin Cofactor assay, the most accepted method for studying VWF in platelet adhesion, we found that polyP activates this role of VWF only at low levels of FVIII, such as in plasmas with chemically depleted FVIII and plasmas from severe hemophilia A patients. Moreover, we demonstrated that FVIII competes with polyP in the activation of VWF. Finally, polyP also increases the binding of VWF to platelets in samples from patients with type 2 and type 3 von Willebrand disease. We propose that polyP may be used in designing new therapies to activate VWF when FVIII cannot be used.<\/jats:p>","DOI":"10.3390\/ijms232214118","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:24:53Z","timestamp":1668565493000},"page":"14118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Polyphosphate Activates von Willebrand Factor Interaction with Glycoprotein Ib in the Absence of Factor VIII In Vitro"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0917-4288","authenticated-orcid":false,"given":"Marcela","family":"Montilla","sequence":"first","affiliation":[{"name":"Research Unit, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain"},{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz, 11009 Cadiz, Spain"},{"name":"Medical School, Universidad Cooperativa de Colombia, Villavicencio 500003, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Atienza-Navarro","sequence":"additional","affiliation":[{"name":"Research Unit, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain"},{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz, 11009 Cadiz, Spain"},{"name":"Department of Biomedicine, Biotechnology, and Public Health, Medical School, Universidad de C\u00e1diz, 11003 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3720-259X","authenticated-orcid":false,"given":"Francisco Jose","family":"Garc\u00eda-Cozar","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz, 11009 Cadiz, Spain"},{"name":"Department of Biomedicine, Biotechnology, and Public Health, Medical School, Universidad de C\u00e1diz, 11003 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6802-0572","authenticated-orcid":false,"given":"Carmen","family":"Castro","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz, 11009 Cadiz, Spain"},{"name":"Department of Biomedicine, Biotechnology, and Public Health, Medical School, Universidad de C\u00e1diz, 11003 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco Javier","family":"Rodr\u00edguez-Martorell","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hospital Universitario Virgen del Roc\u00edo, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0748-5015","authenticated-orcid":false,"given":"Felix A.","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Research Unit, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain"},{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n Biom\u00e9dica de C\u00e1diz, 11009 Cadiz, Spain"},{"name":"Department of Biomedicine, Biotechnology, and Public Health, Medical School, Universidad de C\u00e1diz, 11003 Cadiz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44250","DOI":"10.1074\/jbc.M406261200","article-title":"Human Platelet Dense Granules Contain Polyphosphate and Are Similar to Acidocalcisomes of Bacteria and Unicellular Eukaryotes","volume":"279","author":"Ruiz","year":"2004","journal-title":"J. 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