Ancrod in systemic lupus erythematosus with thrombosis. Clinical and fibrinolysis effects.

A patient with systemic lupus erythematosus had severe hypertension, rapidly worsening renal failure, and multiple successive thrombotic cerebrovascular and retinal lesions develop. In a kidney biopsy specimen luminal thrombi were demonstrated in arteries and arterioles, without vasculitic or inflammatory changes. The patient's plasma was markedly deficient in both prostacyclin stimulating factor (PSF) and vascular plasminogen activator (VPA), and also contained a potent inhibitor of in vitro urokinase-induced fibrinolysis. Treatment with ancrod resulted in striking reversal of the progressive renal damage and clinical recovery from the thrombotic cerebrovascular and retinal lesions. This clinical improvement was associated with improved renal histologic appearance, correction of the PSF and VPA deficiencies, and disappearance of the urokinase inhibitor. Possible mechanisms of action of ancrod are discussed.

Deficiency of a plasma factor stimulating vascular prostacyclin generation in patients with lupus nephritis and glomerular thrombi and its correction by ancrod: in-vivo and in-vitro observations.

Glomerular thrombi occur frequently in active lupus nephritis. Their presence has been correlated with low platelet counts and with subsequent development of glomerular sclerosis. We have examined the plasma PGI2 generating capacity of 8 patients with active lupus nephritis with thrombi that were to undergo defibrination therapy with ancrod. PGI2 generation by these plasma samples was significantly decreased as compared both to normals and to 6 individuals with lupus nephritis and no glomerular thrombi. Significant improvement in the capacity to generate PGI2 was seen in the post-ancrod treatment plasma samples. the pathogenesis of this defect is discussed.

Successful treatment by defibrination with ancrod in a patient with hyperacute renal allograft failure and a deficiency of plasma prostacyclin stimulating factor.

Hyperacute and renal allograft failure, whether due to rejection or other mechanisms, such as perfusion injury, is usually associated with extensive intraglomerular fibrin deposition and allograft loss. Defibrination with ancrod was used to treat a patient with hyperacute renal allograft failure and extensive glomerular fibrin deposition and necrosis. The patient's plasma had normal fibrinolytic activity but a complete absence of the ability to generate prostacyclin-like activity from rat aortic endothelium "in vitro". Treatment was associated with complete recovery of renal function, disappearance of glomerular fibrin, and restoration toward normal of glomerular structure.

Evaluation of treatment in lupus nephritis: effects of prednisone.

Survival of patients with SLE and renal disease has improved in the past 25 yr. There are numerous variables in patients with SLE, and many factors are important in determining outcome. The precise role of any therapeutic regimen in improving survival is unproven. Patients with SLE with normal kidneys, with mesangial changes or with membranous glomerulonephropathy do well whatever treatment is used. Focal and diffuse proliferative glomerulonephritis has a poor prognosis without treatment. Prednisone treatment appears to have improved the survival, but it is probable that treatment with prednisone alone may be less effective than a regimen in which it is combined with cyclophosphamide or nitrogen mustard.