Treatment and prevention of intravascular coagulation with antiserum to endotoxin.

Abstract

Because of the limited success of antibiotics, we have turned to antiserum against endotoxin to prevent one of the most devastating effects of gram-negative bacteremia: disseminated intravascular coagulation (generalized Shwartzman reaction). This reaction was produced in rabbits by iv injection of endotoxin at 24-hr intervals. Rabbit antiserum to endotoxin injected iv 2 hr before the second dose of endotoxin (treatment of disseminated intravascular coagulation) or 96 hr before the first dose (prevention) decreased the reaction from 90% to 18%. Intravascular coagulation was also prevented by antiserum to both heterologous bacteria and side-chain-deficient mutants, by the 19S immunoglobulins of antisera, and by hyperimmune globulin treated with mercaptoethanol and iodoacetate. Passive protection lasted for at least 30 days. Antiserum prevented the precipitous drop in fibrinogen and platelets that accompanies deposition of fibrin in the glomerulus and elsewhere. These findings indicate that protection by antiserum is independent of antibody to O antigen, does not require complement, and prevents the coagulation disturbances induced by endotoxin.