Lupus nephritis with thrombosis and abnormal fibrinolysis: effect of ancrod.
Recent evidence demonstrates that coagulation plays a role in mediating glomerular damage in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis. Because of its beneficial effect in experimental glomerulonephritis, we treated patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis with ancrod, a drug known to lower fibrinogen levels and thought to activate fibrinolysis. Our patients had unusually severe renal disease; renal function was deteriorating in many. Before ancrod, vascular plasminogen activator levels were low, and levels of an inhibitor of plasminogen activation were elevated. Some patients had elevated plasmin inhibitor levels. Results were considered in two groups. In 13 patients characterized as fibrinolysis responders, the low vascular plasminogen activator and increased plasminogen activation inhibitor levels normalized. After ancrod, striking resolution of microvascular thrombosis occurred, which was associated with some improvement in renal function and blood pressure control. In five patients characterized as fibrinolysis nonresponders and who also had an elevated plasmin inhibitor (alpha 2-antiplasmin) level, normalization of fibrinolysis did not occur. There was little change in microvascular thrombosis, renal function, or blood pressure control in the fibrinolysis nonresponders. These preliminary observations demonstrate a disorder of fibrinolysis in patients with systemic lupus erythematosus with microvascular thrombi in the kidney. Ancrod therapy reverses this disorder rapidly in patients with a normal level of plasmin inhibitor and may lead to repair of glomerular damage.
D000293:Adolescent; D000328:Adult; D000721:Ancrod / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure; D004341:Drug Evaluation; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005500:Follow-Up Studies; D005921:Glomerulonephritis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013927:Thrombosis / Q000150:complications*
D000721:Ancrod