FACTOR IX CONCENTRATES ARE THROMBOGENIC AT HIGH DOSES IN DOGS
A canine model has recently been established to assess the potential thrombogenicity of intravenously infused blood products. Elevated plasma levels of fibrinopeptide A (FpA) were identified as the most sensitive indicator of a thrombogenic response, and this was the only parameter to change significantly when issued batches of factor IX (II + X) concentrate were infused at a dose of 100 iu/kg. After infusion of 200 iu/kg, however, plasma FpA concentrations and FDP titres rose, the APTT was prolonged, and the platelet count and fibrinogen level fell. At this dose, therefore, FIX concentrates which were not identified by in vitro tests as potentially thrombogenic induced a response when infused into dogs.A batch of FIX concentrate which failed the criteria for in vitro thrombogenicity and was therefore not issued for routine use was infused at 100 iu/kg. Plasma FpA levels rose as did the FDP titre, and fibrinogen concentrations fell, but the APTT was only slightly prolonged. The thrombogenic response to 200 iu/kg of issued FIX concentrate was at least as severe as that following infusion of 100 iu/kg of this rejected batch.Thus, there is a threshold dose of FIX concentrate above which a severe thrombogenic response can ensue, and the current in vitro tests may not be a reliable indicator of potential thrombogenicity when FIX concentrates are infused at high doses. This should be taken into account when administering unusually high doses, particularly to patients who may have reduced levels of circulating protease inhibitors.