Contribution of fibrin stabilization to clot strength. Supplementation of factor XIII-deficient plasma with the purified zymogen

Abstract

The contribution of fibrin stabilization to clot strength, measured as the static elastic modulus, was evaluated in human plasma by two independent procedures. In the first approach, amine inhibitors of fibrin stabilization were examined for their effects on the rigidity of normal plasma clots. It is a unique property of these inhibitors that they do not interfere with the reversible aggregation of fibrin molecules, i.e., do not delay clotting time, but selectively prevent only the formation of γ-glutamyl-ε-lysine protein-to-protein linkages. Though the compounds tested were of different chemical structures and potencies, a fivefold reduction in clot strength was obtained in each instance. This value of 20% of normal seems to correspond to the rigidity of the Factor XIII-deficient plasma clot because, as demonstrated by the second approach, when a plasma specimen that genetically lacked the fibrin stabilizing factor was supplemented by the addition of measured amounts of the purified zymogen, a fivefold increase in clot strength could be achieved. The described procedure of evaluating Factor XIII in terms of correcting the elastic modulus of a deficient plasma clot is considered an important assay for the functional competence of purified preparations of the zymogen for the purpose of therapeutic application.