Isotopic studies of therapeutic anticoagulation with a coagulating enzyme.

The kinetics of the depletion of plasma fibrinogen were studied in seven patients who received fibrinogen-(131)I 1 hr before an intravenous injection of the coagulating enzyme (CE) derived from the venom of the pit viper, Agkistrodon rhodostoma. Disappearance of the clottable radioactivity labeled fibrinogen from the circulation conformed to an exponential decay with an average half-life of 0.85 hr. The mean clearance rate for protein-bound radioactivity, composed of fibrinogen and it's split products, was 12% of the intravascular pool per hour. The breakdown products of fibrin produced by CE inhibited polymerization of fibrin in vitro. Studies in five patients performed between the 3rd and 10th day following the administration of CE revealed that the absolute catabolic rates of fibrinogen were subnormal initially, but gradually increased as the fibrinogen concentration returned to normal. In rabbits, after the administration of CE, regeneration of the fibrinogen pool was markedly prolonged. This delayed regeneration time was not influenced by an excess of antivenene, but rapid regeneration to pretreatment values of plasma fibrinogen was immediately initiated by stimulating fibrinogen synthesis with subcutaneous turpentine.