title: Adhesion of Blood Clots Can Be Enhanced When Copolymerized with a Macromer That Is Crosslinked by Coagulation Factor XIIIa.
abstract: The adhesion of blood clots to blood vessels, such as through the adhesion of fibrin, is essential in hemostasis. While numerous strategies for initiating clot formation and preventing clot lysis are being developed to create improved hemostatic agents, strategies for enhancing clot adhesion have not been widely explored. Here, we show that adhesion of blood clots can be increased by adding a previously characterized synthetic polymer that is crosslinked by coagulation factor XIIIa during clotting. Addition of the polymer to normal plasma increased the adhesive strength of clots by 2-fold. It also recovered the adhesive strength of nonadhesive fibrinogen-deficient whole blood clots from <0.06 kPa to 1.9 ± 0.14 kPa, which is similar to the adhesive strength of a fibrinogen-rich clot (1.8 ± 0.64 kPa). The polymer also enabled plasma clots to remain adhered under fibrinolytic conditions. By demonstrating that the adhesive strength of clots can be increased with a synthetic material, this provides a potential strategy for creating advanced hemostatic materials, such as treatments for fibrinogen deficiency in trauma-induced coagulopathy.
authors.affiliation: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, and ‡Centre for Blood Research, Department of Pathology and Laboratory Medicine, and the Department of Chemistry, University of British Columbia , Vancouver, BC, Canada.
authors.forename: Karen Y T
authors.initials: KY
authors.lastname: Chan
authors.affiliation: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, and ‡Centre for Blood Research, Department of Pathology and Laboratory Medicine, and the Department of Chemistry, University of British Columbia , Vancouver, BC, Canada.
authors.forename: Chunyi
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, and ‡Centre for Blood Research, Department of Pathology and Laboratory Medicine, and the Department of Chemistry, University of British Columbia , Vancouver, BC, Canada.
authors.forename: Erika M J
authors.initials: EM
authors.lastname: Siren
authors.affiliation: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, and ‡Centre for Blood Research, Department of Pathology and Laboratory Medicine, and the Department of Chemistry, University of British Columbia , Vancouver, BC, Canada.
authors.forename: Jeanne C Y
authors.initials: JC
authors.lastname: Chan
authors.affiliation: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, and ‡Centre for Blood Research, Department of Pathology and Laboratory Medicine, and the Department of Chemistry, University of British Columbia , Vancouver, BC, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Boschman
authors.affiliation: Michael Smith Laboratories and Department of Biochemistry and Molecular Biology, and ‡Centre for Blood Research, Department of Pathology and Laboratory Medicine, and the Department of Chemistry, University of British Columbia , Vancouver, BC, Canada.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Kastrup
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D026122:Factor XIIIa / Q000378:metabolism*; D015241:Fibrinogens, Abnormal / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010949:Plasma / Q000187:drug effects / Q000378:metabolism*; D011108:Polymers / Q000494:pharmacology*; D013927:Thrombosis / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D015241:Fibrinogens, Abnormal; D011108:Polymers; C527521:fibrinogen gamma'; D026122:Factor XIIIa