Fibrinolysis in vivo Predicts a Favorable Outcome in Patients with Small Vessel Thrombi: Observations in Patients with Glomerular Thrombi during Treatment with Ancrod

Abstract

Fibrin deposits injure small vessels. To evaluate the effect of fibrinolysis, patients with glomerular diseases having glomerular thrombi received the snake venom enzyme, ancrod, for 14 days. Within 48 hours, the mean level of fibrin/fibrinogen degradation products( FOP) was very high, and bimodally distributed, defining lowln = 11) and high(n = 18) FOP responses. In the low FOP group, the FOP rise and fibrinogen decrease were linearly related, suggesting that most FOP derived from fibrinogen degradation. Renal effects were minimal. In the high FOP group, the FOP level was not explained by fibrinogen degradation alone, indicating fibrin dissolution. Renal function improved, proteinuria increased, and glomerular fibrin deposition decreased. Tissue type plasminogen activator, released by ancrod-frbim from endothelial cells, converts fibrin-bound plasminogen to palsmin, which degrades fibim. Alpha--antiplasrnin, the most effective known inhibitor of fibrinolysis, was elevated in 9/11 in the low, and 5/18 in the high FOP group. Thus when fibrinolysis occurred, it was associated with rapid favorable effects on renal function and histology.