biostudies-literaturePoole LGNIDDK NIH HHSNHLBI NIH HHSEuropean Hematology AssociationNCI NIH HHSNIGMS NIH HHS2520-2531https://www.ebi.ac.uk/biostudies/studies/S-EPMC8109015biostudies-literatureUnknown137(18)Intravascular fibrin clot formation follows a well-ordered series of reactions catalyzed by thrombin cleavage of fibrinogen leading to fibrin polymerization and cross-linking by factor XIIIa (FXIIIa). Extravascular fibrin(ogen) deposits are observed in injured tissues; however, the mechanisms regulating fibrin(ogen) polymerization and cross-linking in this setting are unclear. The objective of this study was to determine the mechanisms of fibrin polymerization and cross-linking in acute liver injury induced by acetaminophen (APAP) overdose. Hepatic fibrin(ogen) deposition and cross-linking were measured following APAP overdose in wild-type mice, mice lacking the catalytic subunit of FXIII (FXIII-/-), and in FibAEK mice, which express mutant fibrinogen insensitive to thrombin-mediated fibriBloodFactor XIII cross-links fibrin(ogen) independent of fibrin polymerization in experimental acute liver injury.PMC8109015T32 GM092715RG41R01 DK120289R01 DK112778F32 DK121423R01 DK105099R01 CA211098U01 HL143403Pant ACline-Fedewa HMFlick MJKopec AKLuyendyk JPPoole LGGroeneveld DJBaker KSfalseFactor XIII cross-links fibrin(ogen) independent of fibrin polymerization in experimental acute liver injury.Intravascular fibrin clot formation follows a well-ordered series of reactions catalyzed by thrombin cleavage of fibrinogen leading to fibrin polymerization and cross-linking by factor XIIIa (FXIIIa). Extravascular fibrin(ogen) deposits are observed in injured tissues; however, the mechanisms regulating fibrin(ogen) polymerization and cross-linking in this setting are unclear. The objective of this study was to determine the mechanisms of fibrin polymerization and cross-linking in acute liver injury induced by acetaminophen (APAP) overdose. Hepatic fibrin(ogen) deposition and cross-linking were measured following APAP overdose in wild-type mice, mice lacking the catalytic subunit of FXIII (FXIII-/-), and in FibAEK mice, which express mutant fibrinogen insensitive to thrombin-mediated fibri2021-01-01T00:00:00Z2021 May2025-04-04T10:16:31.633Z2025-04-04T10:16:31.633ZS-EPMC81090153356960310.1182/blood.2020007415