Influence of γ′ Fibrinogen Splice Variant on Fibrin Physical Properties and Fibrinolysis Rate

Objective-A splice variant of fibrinogen, γ′, has an altered C-terminal sequence in its gamma chain. This γA/γ′ fibrin is more resistant to lysis than γA/γA fibrin. Whether the physical properties of γ′ and γA fibrin may account for the difference in their fibrinolysis rate remains to be established. Methods and Results-Mechanical and morphological properties of cross-linked purified fibrin, including permeability (Ks, in cm²) and clot stiffness (G′, in dyne/cm²), were measured after clotting γA and γ′ fibrinogens (1 mg/mL). γ′/γ′ fibrin displayed a non-significant decrease in the density of fibrin fibers and slightly thicker fibers than γA/γA fibrin (12±2 fiber/10 ^-3nm³ versus 16±2 fiber/10^-3nm ³ and 274±38 nm versus 257±41 nm for γ′/γ′ and γA/γA fibrin, respectively; P = NS). This resulted in a 20% increase of the permeability constant (6.9±1.7 10^-9 cm² versus 5.5 ± 1.9 10 ^-9 cm², respectively; P = NS). Unexpectedly, γ′ fibrin was found to be 3-times stiffer than γA fibrin (72.6±2.6 dyne/cm² versus 25.1±2.3 dyne/cm ²; P<0.001). Finally, there was a 10-fold decrease of the fibrin fiber lysis rate. Conclusions-Fibrinolysis resistance that arises from the presence of γA/γ′ fibrinogen in the clot is related primarily to an increase of fibrin cross-linking with only slight modifications of the clot architecture.