Analysis of fibrin formation and proteolysis during intravenous administration of ancrod

Ancrod is a purified fraction of venom from the Malayan pit viper, Callosel 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 desAA-fibrin monomer, In addition, a considerable propor tion of desA-profibrin is formed. Production of desA-profibrin is highest a t low concentrations of ancrod, whereas desA-profibrin is rapidly converted to desAA-fibrin at higher concentrations of ancrod, Both desA-profibrin an d desAA-fibrin monomers form fibrin complexes. A certain proportion of comp lexes carries exposed fibrin polymerization sites E-A, indicating that the terminal component of the protofibril is a desAA-fibrin monomer unit. Solub le fibrin complexes potentiate tissue-type plasminogen activator-induced pl asminogen activation. Significant amounts of plasmin are formed when solubl e fibrin in plasma reaches a threshold concentration, leading to the proteo lytic degradation of fibrinogen and fibrin. In the present setting, high co ncentrations of soluble fibrin are detected after 1 hour of ancrod infusion , whereas a rise in fibrinogen and fibrin degradation products, and plasmin -alpha(2)-plasmin inhibitor complex levels is first detected after 2 hours of ancrod infusion. Ancrod treatment also results in the appearance of cros s-inked fibrin degradation product D-dimer in plasma. (Blood. 2000;96: 2793 -2802) (C) 2000 by The American Society of Hematology.