Thromboelastograph assay for measuring the mechanical strength of fibrin sealant clots

In order to provide sustained hemostasis or tissue sealing, fibrin sealants must generate adhesive clots with mechanical properties capable of resisti ng forces, such as shear, that might break or tear the clot. Commercial pre parations of fibrin sealants should generate clots of adequate and consiste nt mechanical strength. The mechanical strength of fibrin sealants is often measured as bonding strength in in vivo or ex vivo animal wound models. Th ese tests can be useful predictors of clinical efficacy. However, these, as well as many in vitro tensile strength tests for fibrin sealant, tend to b e laboratory specific and require extensive reagent preparation time and an alyst training. The thromboelastograph has historically been used to screen for plasma protein and platelet disorders that lead to defective clot form ation. The authors have developed a simple in vitro test, using a standard thromboelastograph that can provide reliable, reproducible information on t he rheology of clots generated by fibrin sealant preparations. Using this m ethod, 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 concen tration of the fibrin crosslinking proenzyme, factor XIII. Sealants contain ing 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 dist inguished between thrombin-catalyzed clot formation and other fibrinogen cl otting mechanisms as evidenced by the significantly lower shear strength as sociated with batroxobin-generated fibrin clots.