The effects of a 14-day course of
ancrod on fibrinolysis, renal function and structure, and immunologic findings are reported in 37 patients with
glomerulonephritis. Patients were divided into two groups. In the first, the level of
fibrin degradation products within 48 h was relatively low (less than 1 mg/ml). In these patients there was a linear relationship between changes in levels of
fibrin degradation products and
fibrinogen, suggesting that
fibrin degradation products derived from
ancrod-cleaved-
fibrinogen in the circulating pool; in most, level of plasma alpha 2-antiplasmin before treatment was elevated. In the second, the level of
fibrin degradation products within 48 h was high (greater than 1 mg/ml). Compared with the change in
fibrinogen, a disproportionate increase in levels of
fibrin degradation products suggested that a significant amount derived from sources other than
plasmin digested
ancrod-cleaved-
fibrinogen, thus reflecting effective fibrinolysis, perhaps also in tissues; in most, the level of plasma alpha 2-antiplasmin was normal before treatment. In those with initial high levels of
fibrin degradation products, higher levels persisted throughout treatment, changes in other fibrinolysis components were greater, and
plasminogen activator inhibitor levels became normal. In patients with initial high but not with initial low response in
fibrin degradation products renal function improved within 24 to 48 h and continued to improve thereafter; there was an immediate but temporary increase in
proteinuria. Microvascular
thrombosis decreased significantly, indicating effective removal of
fibrin from glomeruli. The relation of early fibrinolysis to changes in immunologic and histopathologic findings was analyzed in patients with
lupus nephritis. With
ancrod, there was an increase toward normal of serum C3 and C4, a decrease in serum Igs,
gamma globulin and
anti-dsDNA antibody and in glomerular C3 and Ig deposits, suggesting that
ancrod had favorable effects on
immunologic factors. There were no clinical differences in patients with initial high and low responses, but the relationship of microvascular and inflammatory indexes before treatment differed. Initial renal biopsies and those
after treatment were carried out on average 28 days apart. Inflammatory and microvascular indexes and glomerular thrombi decreased in patients with initial high levels of
fibrin degradation products; fibrosclerosis index and glomerular
sclerosis increased in patients with initial low levels of
fibrin degradation products. Fibrinolysis expressed as the 48 h (
fibrin degradation products/
fibrinogen) ratio, correlated inversely with change in fibrosclerosis index and glomerular
sclerosis in the whole group, and especially in those with initial high levels of
fibrin degradation products.(ABSTRACT TRUNCATED AT 400 WORDS)