Pharmacologic evaluation of factor XIIIa*-like enzyme activity in equine plasma as a potential therapeutic avenue for the inhibition of fibrinous tissue.

Several pharmaceutical compounds were evaluated for their ability to selectively inhibit activated coagulation factor-XIII-like enzyme activity (eg, XIIIa*) in pooled equine plasma. Presence of coagulation factor-XIIIa*-like enzyme activity in plasma was established by assay procedures involving incorporation of the fluorescent amine compound, monodansylcadaverine, into purified casein, which served as a protein substrate. Pharmaceuticals inhibitory to coagulation factor-XIIIa*-like enzyme activity were recognized by plasma gel formation of high spectrophotometric transmittance (transparency), solubility of transparent fibrin gels in concentrated urea solution, in conjunction with simultaneous depletion of native fibrinogen fractions, and production of fibrin monomer. Compounds acting primarily as anticoagulants were recognized by lack of plasma gel formation, but retaining high spectrophotometric transmittance and no detectable depletion of native fibrinogen fractions. Compounds failing to inhibit either thrombin-mediated fibrinogen-fibrin transformation (ie, coagulation) or coagulation factor-XIIIa*-like enzyme activity were recognized by opaque plasma gels caused by fibrin polymerization, low spectrophotometric transmittance values, and coinciding with depletion of native fibrinogen fractions. Pharmaceuticals capable of exerting selective inhibition of coagulation factor-XIIIa*-like enzyme activity were further classified as competitive inhibitors of phase 1 (carbamide) or phase 2 (terminal amine) of the transglutamination process.