Ancrod: normalization of fibrinolytic enzyme abnormalities in patients with systemic lupus erythematosus and lupus nephritis.
Ancrod is a thrombinlike enzyme from Malayan pit viper (Agkistrodon rhodostoma) venom that has a selective enzyme substrate specificity for fibrinogen. Unlike thrombin, it splits only fibrinopeptide A from the fibrinogen molecule and does not activate factor XIII. Simultaneously with the occurrence of hypofibrinogenemia there is a reduction of plasma plasminogen and a rise in fibrin degradation products, suggesting secondary recruitment of the fibrinolytic enzyme system. Ancrod was given to 18 patients with systemic lupus erythematosus and glomerular and vascular microthrombi. Before treatment vascular plasminogen activator (VPA) was low or unmeasurable in 14, an inhibitor of urokinase-induced plasminogen activation (IPA) was elevated in 18, and an inhibitor of plasmin (PI) was elevated in five. Ancrod treatment resulted in prompt normalization of IPA levels in 13 patients; they were classified as fibrinolysis responders. In five patients IPA levels remained elevated throughout treatment with ancrod; they were classified as fibrinolysis nonresponders. In these five the PI level was elevated before treatment and decreased slowly toward the normal range during ancrod administration. The PI did not appear related to the nonspecific serine protease inhibitors, and was shown to be identical with alpha 2-antiplasmin. In the fibrinolysis responders serial histologic studies showed a striking decrease of disappearance of microvascular thrombosis; in the fibrinolysis nonresponders microvascular thrombosis persisted. The action of ancrod is discussed.
D000328:Adult; D000721:Ancrod / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005340:Fibrinogen / Q000097:blood; D005342:Fibrinolysis / Q000187:drug effects*; D005921:Glomerulonephritis / Q000097:blood / Q000188:drug therapy*; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D010960:Plasminogen Activators / Q000097:blood; D015849:Plasminogen Inactivators; D013927:Thrombosis / Q000188:drug therapy
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D005340:Fibrinogen; D000721:Ancrod; D010960:Plasminogen Activators