Fibrinogen concentrations compared with total bleeding.

Nadir fibrinogen concentrations (top) are compared with total bleeding (bottom) in animals receiving TPA or plasmin. Control values for nadir fibrinogen concentrations, at 0 mg/kg of plasmin or TPA, were determined in plasma samples obtained before infusion (at −30 and 0 minutes). Control values for total bleeding were determined in the 5 rabbits that received saline (mean of 50 determinations, 2.25 ± 0.4 minutes). Decrease in plasma fibrinogen concentration with plasmin was dose-dependent and more profound than with TPA, which did not alter the fibrinogen concentration significantly from the pretreatment level. Nevertheless, TPA induced bleeding in a stepwise manner at increasing dosages, unrelated to the plasma fibrinogen concentration. Plasmin did not induce excessive bleeding at 4 or 6 mg/kg. At a plasmin dose of 8 mg/kg, the nadir fibrinogen concentration dropped below the lower limit of quantification, in association with the appearance of excessive bleeding.