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Putting polyphosphates to the test: evidence against platelet-induced activation of factor XII
Linköping University, Linköping, Sweden.
Linköping University, Linköping, Sweden.
Linköping University, Linköping, Sweden.ORCID iD: 0000-0002-6681-0546
Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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2013 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 122, no 23, p. 3818-3824Article in journal (Refereed) Published
Abstract [en]

The recent claim that stimulated platelets activate the intrinsic pathway of coagulation by the release of polyphosphates has been considered a breakthrough in hemostasis research. In little more than 3 years, the original publication by Müller et al has been cited >100 times. However, none of the citing articles has sought to independently validate this potentially paradigm-shifting concept. To this end, we performed extensive experimentation in vitro and in vivo in an attempt to verify the claim that factor XII (FXII) is primarily activated by stimulated platelets. In contrast to the original assertion, platelet-derived polyphosphates were found to be weak activators of FXII, with a FXIIa-generating activity of <10% compared with equivalent concentrations of kaolin. Using different coagulation assays, it was shown that platelet contribution to whole blood coagulation was unrelated to the generation of activated FXII in vitro. Additionally, key results used to verify the hypothesis in the original study in vivo were found to be irreproducible. We conclude that platelet-derived polyphosphates are not physiologically relevant activators of FXII.

Place, publisher, year, edition, pages
Washington, USA: The American Society of Hematology , 2013. Vol. 122, no 23, p. 3818-3824
National Category
Medical and Health Sciences Hematology
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URN: urn:nbn:se:oru:diva-48099DOI: 10.1182/blood-2013-05-499384ISI: 000329735000021PubMedID: 23896408Scopus ID: 2-s2.0-84892890568OAI: oai:DiVA.org:oru-48099DiVA, id: diva2:901420
Available from: 2016-02-08 Created: 2016-02-08 Last updated: 2018-04-05Bibliographically approved

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Ström, Jakob O.Ramström, Sofia

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