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dc.contributor.authorHeestermans, Marco
dc.contributor.authorNaudin, Clement
dc.contributor.authorMailer, Reiner K.
dc.contributor.authorKonrath, Sandra
dc.contributor.authorKlaetschke, Kristin
dc.contributor.authorJämsä, Anne
dc.contributor.authorFrye, Maike
dc.contributor.authorDeppermann, Carsten
dc.contributor.authorPula, Giordano
dc.contributor.authorKuta, Piotr
dc.contributor.authorFriese, Manuel A.
dc.contributor.authorGelderblom, Mathias
dc.contributor.authorSickmann, Albert
dc.contributor.authorPreston, Roger J. S.
dc.contributor.authorNofer, Jerzy-Roch
dc.contributor.authorRose-John, Stefan
dc.contributor.authorButler, Lynn
dc.contributor.authorSalomon, Ophira
dc.contributor.authorStavrou, Evi X.
dc.contributor.authorRenné, Thomas
dc.date.accessioned2022-01-06T08:42:39Z
dc.date.available2022-01-06T08:42:39Z
dc.date.issued2021-09-22
dc.description.abstractContact activation refers to the process of surface-induced activation of factor XII (FXII), which initiates blood coagulation and is captured by the activated partial thromboplastin time (aPTT) assay. Here, we show the mechanism and diagnostic implications of FXII contact activation. Screening of recombinant FXII mutants identified a continuous stretch of residues Gln317–Ser339 that was essential for FXII surface binding and activation, thrombin generation and coagulation. Peptides spanning these 23 residues competed with surface-induced FXII activation. Although FXII mutants lacking residues Gln317–Ser339 were susceptible to activation by plasmin and plasma kallikrein, they were ineffective in supporting arterial and venous thrombus formation in mice. Antibodies raised against the Gln317–Ser339 region induced FXII activation and triggered controllable contact activation in solution leading to thrombin generation by the intrinsic pathway of coagulation. The antibody-activated aPTT allows for standardization of particulate aPTT reagents and for sensitive monitoring of coagulation factors VIII, IX, XI.en_US
dc.identifier.citationHeestermans, Naudin C, Mailer, Konrath, Klaetschke, Jämsä, Frye, Deppermann, Pula, Kuta, Friese, Gelderblom, Sickmann, Preston, Nofer, Rose-John, Butler LB, Salomon, Stavrou, Renné. Identification of the factor XII contact activation site enables sensitive coagulation diagnostics. Nature Communications. 2021;12(1)en_US
dc.identifier.cristinIDFRIDAID 1943195
dc.identifier.doi10.1038/s41467-021-25888-7
dc.identifier.issn2041-1723
dc.identifier.urihttps://hdl.handle.net/10037/23606
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.relation.journalNature Communications
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Hematology: 775en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Hematologi: 775en_US
dc.titleIdentification of the factor XII contact activation site enables sensitive coagulation diagnosticsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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