Analysis of fibrin formation and proteolysis during intravenous administration of ancrod

Ancrod is a purified fraction of venom from the Malayan pit viper, Callosei asma rhodostoma, currently under investigation for treatment of acute ische mic stroke. Treatment with ancrod leads to fibrinogen depletion. The presen t study investigated the mechanisms leading to the reduction of plasma fibr inogen concentration. Twelve healthy volunteers received an intravenous inf usion of 0.17 U/kg body weight of ancrod for 6 hours. Blood samples were dr awn and analyzed before and at various time points until 72 hours after sta rt of infusion. Ancrod releases fibrinopeptide A from fibrinogen, leading t o the formation of des-AA-fibrin monomer, In addition, a considerable propo rtion of desA-profibrin is formed, Production of desA-profibrin is highest at low concentrations of ancrod, whereas desA-profibrin is rapidly converte d to desAA-fibrin at higher concentrations of ancrod, Both desA-profibrin a nd desAA-fibrin monomers form fibrin complexes, A certain proportion of com plexes carries exposed fibrin polymerization sites E-A, indicating that the terminal component of the protofibril is a desAA-fibrin monomer unit. Solu ble fibrin complexes potentiate tissue-type plasminogen activator-induced p lasminogen activation. Significant amounts of plasmin are formed when solub le fibrin in plasma reaches a threshold concentration, leading to the prote olytic degradation of fibrinogen and fibrin, In the present setting, high c oncentrations of soluble fibrin are detected after 7 hour of ancrod infusio n, whereas a rise in fibrinogen and fibrin degradation products, and plasmi n-alpha (2)-plasmin inhibitor complex levels is first detected after 2 hour s of ancrod infusion. Ancrod treatment also results in the appearance of cr oss-linked fibrin degradation product D-dimer in plasma. (C) 2000 by The Am erican Society of Hematology.