Tissue plasminogen activator therapy of glomerular thrombi in the Shwartzman reaction

To study the effect of tissue plasminogen activator (TPA) therapy on glomerular fibrin deposition in the generalized Shwartzman reaction, rabbits were given an intravenous injection of TPA immediately following or three, four, or five hours after the second injection of endotoxin. Animals were sacrificed six hours after the second dose of endotoxin. Glomerular fibrin deposition was reduced in animals receiving TPA four hours after the second injection of endotoxin and was absent in animals receiving TPA five hours after the second dose of endotoxin. Glomerular fibrinolytic activity was reduced following development of the generalized Shwartzman reaction but was normal in animals that received TPA five hours after the second injection of endotoxin. TPA did not produce a systemic fibrinolytic state and did not prevent the decline in hematologic and coagulation factors typical of the Shwartzman reaction, despite the elimination of glomerular fibrin. These results suggest that TPA effectively removes glomerular thrombi in the generalized Shwartzman reaction and infers that TPA may be of value in the treatment of human diseases with similar pathology, such as the hemolytic uremic syndrome.