Mechanism of ancrod anticoagulation. A direct proteolytic effect on fibrin.
Fibrin formed in response to ancrod, reptilase, or thrombin was reduced by beta-mercaptoethanol and examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was found that ancrod progressively and totally digested the alpha-chains of fibrin monomers at sites different than plasmin; however, further digestion of fibrin monomers by either reptilase or thrombin was not observed. Highly purified ancrod did not activate fibrin-stabilizing factor (FSF); however, the reptilase preparation used in these experiments, like thrombin, activated FSF and thereby promoted cross-link formation. Fibrin, formed by clotting purified human fibrinogen with ancrod, reptilase, or thrombin for increasing periods of time in the presence of plasminogen, was incubated with urokinase and observed for complete lysis. Fibrin formed by ancrod was strikingly more vulnerable to plasmin digestion than was fibrin formed by reptilase or thrombin. The lysis times for fibrin formed for 2 hr by ancrod, reptilase, or thrombin were 18, 89, and 120 min, respectively. Evidence was also obtained that neither ancrod nor reptilase activated human plasminogen. These results indicate that fibrin formed by ancrod is not cross-linked and has significantly degraded alpha-chains: as expected, ancrod-formed fibrin is markedly susceptible to digestion by plasmin.
D000925:Anticoagulants / Q000494:pharmacology*; D001665:Binding Sites; D004591:Electrophoresis, Polyacrylamide Gel; D005176:Factor XIII; D005337:Fibrin / Q000032:analysis; D005340:Fibrinogen / Q000378:metabolism; D005341:Fibrinolysin / Q000494:pharmacology; D005342:Fibrinolysis; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D010447:Peptide Hydrolases / Q000494:pharmacology*; D010958:Plasminogen / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology*
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D014688:Venoms; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D005176:Factor XIII; D010447:Peptide Hydrolases; D013917:Thrombin; D005341:Fibrinolysin