title: Feedback activation of factor XI by thrombin does not occur in plasma.
abstract: In this study, we tested the hypothesis that factor XI (FXI) activation occurs in plasma following activation of the extrinsic pathway by thrombin-mediated feedback activation. We used two different assays: (i) a direct measurement of activated FXI by ELISA and (ii) a functional assay that follows the activation of the coagulation cascade in the presence or absence of a FXI inhibiting antibody by monitoring thrombin activity. We failed to detect any FXI activation or functional contribution to the activation of the coagulation cascade in platelet poor or platelet-rich plasma, when activation was initiated by thrombin or tissue factor. Additionally, we found that, in the absence of a contact system inhibitor during blood draw, contact activation of FXI can mistakenly appear as thrombin- or tissue-factor-dependent activation. Thus, activation of FXI by thrombin in solution or on the surface of activated platelets does not appear to play a significant role in a plasma environment. These results call for reevaluation of the physiological role of the contact activation system in blood coagulation.
authors.affiliation: Department of Chemical Enzymology, Bristol-Myers-Squibb Company, 311 Pennington-Rocky-Hill Road, Pennington, NJ 08534, USA.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Pedicord
authors.forename: Dietmar
authors.initials: D
authors.lastname: Seiffert
authors.forename: Yuval
authors.initials: Y
authors.lastname: Blat
mesh_terms: D001792:Blood Platelets / Q000378:metabolism; D005172:Factor XI / Q000378:metabolism*; D005173:Factor XI Deficiency / Q000378:metabolism; D025461:Feedback, Physiological; D006801:Humans; D010949:Plasma / Q000378:metabolism; D010974:Platelet Aggregation; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D005172:Factor XI; D013925:Thromboplastin; D013917:Thrombin