title: Thromboelastograph assay for measuring the mechanical strength of fibrin sealant clots.
abstract: In order to provide sustained hemostasis or tissue sealing, fibrin sealants must generate adhesive clots with mechanical properties capable of resisting forces, such as shear, that might break or tear the clot. Commercial preparations of fibrin sealants should generate clots of adequate and consistent mechanical strength. The mechanical strength of fibrin sealants is often measured as bonding strength in in vivo or ex vivo animal wound models. These tests can be useful predictors of clinical efficacy. However, these, as well as many in vitro tensile strength tests for fibrin sealant, tend to be laboratory specific and require extensive reagent preparation time and analyst training. The thromboelastograph has historically been used to screen for plasma protein and platelet disorders that lead to defective clot formation. The authors have developed a simple in vitro test, using a standard thromboelastograph that can provide reliable, reproducible information on the rheology of clots generated by fibrin sealant preparations. Using this method, the shear strength of fibrin sealant clots was measured and shown to correlate with the fibrinogen, but not the thrombin, concentration in the sealant. Shear strength was also shown to correlate with the sealant concentration of the fibrin cross-linking proenzyme, factor XIII. Sealants containing lysine, which can act as an alternate substrate for factor XIII enzyme and prevent efficient fibrin chain cross-linking, were shown by this method to generate clots of substantially reduced shear strength. The method distinguished between thrombin-catalyzed clot formation and other fibrinogen clotting mechanisms as evidenced by the significantly lower shear strength associated with batroxobin-generated fibrin clots.
authors.affiliation: Alpha Therapeutic Corporation, Los Angeles, California 90032, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Glidden
authors.forename: C
authors.initials: C
authors.lastname: Malaska
authors.forename: S W
authors.initials: SW
authors.lastname: Herring
mesh_terms: D012103:Batroxobin / Q000494:pharmacology / Q000502:physiology; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000379:methods / Q000592:standards; D004305:Dose-Response Relationship, Drug; D005176:Factor XIII / Q000494:pharmacology / Q000502:physiology; D015718:Fibrin Tissue Adhesive / Q000032:analysis* / Q000592:standards; D005340:Fibrinogen / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D008239:Lysine / Q000494:pharmacology / Q000502:physiology; D013314:Stress, Mechanical; D013916:Thrombelastography / Q000379:methods* / Q000592:standards; D013917:Thrombin / Q000494:pharmacology / Q000502:physiology; D013997:Time Factors
chemical_list: D015718:Fibrin Tissue Adhesive; D005340:Fibrinogen; D005176:Factor XIII; D012103:Batroxobin; D013917:Thrombin; D008239:Lysine