Human Factor IX in Animals: Kinetics from Isolated, Radiolabelled Protein and Platelet Destruction following Crude Concentrate Infusions

Abstract

Crude, concentrated and isolated, labelled human factor IX was prepared and infused into animals. Initially, two dogs with severe haemophilia B received both preparations and factor IX clotting activity and label survived well. Kinetic parameters fit a two-compartment open model. For 12 infusions of concentrates into normal baboons, clotting and antigen data again fit the model. Similar kinetics, with less variability, were found for nine infusions of [125I]factor IX. Radioactivity of the first post-infusion samples was > 90% precipitated in the double antibody system with an average of 84% of counts adsorbable to barium citrate. Compared to plasma, barium adsorbable counts gave a shorter t1/2 beta-elimination phase suggesting a small recirculating 125iodide pool. When [125I]factor IX was rechromatographed over heparin-agarose, variable amounts of altered, labelled protein were present; this species was more rapidly cleared from plasma post-infusion. Twelve infusions of crude concentrates into baboons were given to animals whose platelets had been labelled with 51Cr. Platelet counts as well as survival were then followed. For seven of these animals, mean counts decreased and the labelled platelets were destroyed, to an average of 21%, during the first 4 h post-infusion. Subsequent platelet survival was normal. Three infusions of gel-filtered, crude concentrates and two infusions of 'activated' commercial concentrates did not significantly alter platelet survival.