IN-VIVO STUDIES OF ACTIVATED PORCINE FACTOR-VIII

The haemostatic effectiveness of activated FVIII was compared to that of non-activated FVIII in a cross-over study in st canine model of hae mophilia. Activation of FVIII in porcine concentrate was achieved by t he addition of 3 X 10(-5) IU thrombin per mi of concentrate, which gav e consistent increases in 1-stage FVIII activity of 13- to 14-fold and slow decay. The haemostatic effect was monitored by measurements of t he cuticle bleeding time 10 and 45 min after infusion and there were n o consistent differences between the activated and non-activated conce ntrates. One-stage factor VIII assays on plasmas 5 min after infusion showed identical mean values for activated and non-activated concentra tes, indicating that most of the higher activity observed in vitro had disappeared rapidly from the circulation. These results suggest that controlled activation of FVIII by thrombin, which increases its activi ty in 1-stage assays, is unlikely to be of therapeutic benefit. For th erapeutic concentrates which may contain small amounts of activated FV III, the 1-stage assay may be an unreliable guide to their therapeutic effect.