Effects of Thorotrast upon the Reactivity and Intravascular Disappearance Rate of Fibrinogen in the Rabbit ∗

Abstract

Summary and Conclusions

The data presented above confirm and extend previous observations (1, 2, 13) that Thorotrast markedly alters the reactivity of fibrinogen. Microscopic examination of clots from plasma incubated in vitro with Thorotrast revealed a progressive defect in fibrin strand formation. Thrombin times were prolonged for at least 10 hours after the intravenous injection into rabbits of the dosage (3 ml/kg) used to produce “reticuloendothelial blockade.” When plasma from blood drawn after the administration of Thorotrast was clotted, most of the radioactivity of the Thorotrast was found in the clot. This suggests that Thorotrast may circulate largely as a complex with fibrinogen.

Despite these marked effects, Thorotrast did not increase the rate of intravascular disappearance of ¹³¹I-labeled fibrinogen. Thus, the return of the thrombin time to normal within 1 day after Thorotrast was not associated with the removal of measurable amounts of a Thorotrast-fibrinogen complex or of excess fibrinogen damaged directly or indirectly by Thorotrast. Apparently, as Thorotrast is removed from the circulation, fibrinogen altered by Thorotrast recovers its normal reactivity.

The fibrinogen present in the circulation 3 hours after the administration of Thorotrast was no more susceptible to precipitation in vitro by Liquoid than was normal fibrinogen. This supports the view of Lee and co-workers (12) that Thorotrast has no role other than altering reticuloendothelial function in preparing animals for renal cortical necrosis after Liquoid.

Thorotrast does not induce measurable intravascular clotting. Therefore, the decrease in platelets, Factor V, and Factor VIII observed earlier (2) must represent a direct effect of Thorotrast upon these factors. Endotoxin is normally absorbed from the gut and removed by the reticuloendothelial system (8). In our rabbits, which received a feed containing tetracycline, insufficient endotoxin was absorbed to change the disappearance rate of intravascular fibrinogen after “reticulo-endothelial blockade.” This suggests that in healthy animals, fed a diet supplemented with antibiotic, evidence of increased fibrinogen disappearance after Thorotrast and a second agent may be attributed to an action of the second agent, provided that this agent does not also increase absorption of endotoxin from the gut.