Potentiation of endotoxin-induced consumptive coagulopathy by lead acetate administration.

Since chickens are naturally deficient in several clotting factors normally present in mammalian sera, the ability of lead acetate (PbAc(2)) to sensitize 11-day-old chicks to endotoxin was compared with its ability to sensitize rats. It was found that, although the chicks could tolerate only relatively low doses of PbAc(2), even those doses would produce a greater than 200-fold sensitization to the endotoxin in rats, as compared with little sensitization in the chicks. By using larger doses of PbAc(2), known to maximally sensitize rats to endotoxin, the effect of PbAc(2) sensitization on whole-blood clotting times, platelet counts, plasma factor V and VIII activities, and the appearance of fibrin degradation products was evaluated. It was found that animals treated with lethal doses of endotoxin but no PbAc(2) showed varying degrees of consumptive coagulopathy. On the other hand, the injection of minute quantities of endotoxin into PbAc(2)-sensitized rats invariably resulted in disseminated intravascular coagulation, apparently via a complete activation of the intrinsic pathway. It is concluded that the site of PbAc(2) sensitization to endotoxin is in the blood, and most probably at the level of Hageman factor activation.