Participation of Soluble Fibrin Monomer Complexes and Platelet Factor 4 in the Generalized Shwartzman Reaction

Abstract

The generalized Shwartzman reaction was produced in rabbits by the typical way of 2 consecutive injections of Salmonella typhi endotoxin. Generalized Shwartzman reaction was also induced by “preparation” of the rabbits with epsilon-aminocaproic acid or mercuric chloride intoxication, followed by a single injection of the endotoxin. Significant impairment of blood fibrinolytic activity resulting from inhibition by endotoxin of a release of the kidney plasminogen activator, was demonstrated in the classical generalized Shwartzman reaction. Inhibition of fibrinolysis led to the accumulation of soluble fibrin monomer complexes in the circulation, detectable in plasma by protamine sulfate precipitation. It is postulated that hypercoagulability, regularly occurring in the generalized Shwartzman phenomen, is due to fibrinolysis inhibition. Endotoxin causes release of platelet factor 4 from rabbit blood platelets both in vitro and in vivo. This factor is thought to be responsible for nonenzymatic intravascular precipitation of fibrin from circulating soluble fibrin monomer complexes. Bilateral cortical necrosis in kidneys is due by fibrin deposition resulting from the disturbance in the equillibrium between blood clotting and fibrinolytic systems and the interaction of accumulated soluble fibrin monomer complexes with platelet factor 4. ^* This study was supported by research grant CDC-LP-3 from the Communicable Disease Center, U. S. Public Health Service.