Effect of drug administration on experimental renal glomerular thrombosis

Experimental thrombosis which developed exclusively in glomerular capillary walls was induced in rats by the combined injection of nephrotoxic antiserum (0.2 ml of pooled material) as a preparatory agent and 20 micrograms or more of lipopolysaccharide as a provoking agent. Effects of some antiplatelet and anticoagulant drugs on the glomerular lesions were tested in this experimental glomerular thrombosis. With administration of 2000 units/kg or more of heparin at the time of provoking injection, coagulation time was prolonged for over 5 hr, and the glomerular thrombosis was adequately prevented. Prolongation of prothrombin time (PT) for over 60 sec to prevent thrombosis required warfarin, but with this drug there was only a narrow margin between an effective dose and that which produced a fatal hemorrhage. Low levels of fibrinogen (less than 50 mg/dl) induced by batroxobin seemed to protect partially and high doses of urokinase did not seem to protect from glomerular thrombosis. OP-41483, a derivative of prostacyclin which is about five times more active than PGE1 in inhibiting platelet aggregation, and other anti-platelet drugs except for ticlopidine were not effective in preventing glomerular thrombosis. These findings were in accordance with the fact that thrombocytopenia induced by antiplatelet antiserum did not prevent glomerular thrombosis. Ticlopidine may have a unique and valuable therapeutic potential for the control of this condition.