HIGH-PURITY FACTOR-IX AND PROTHROMBIN COMPLEX CONCENTRATE (PCC) - PHARMACOKINETICS AND EVIDENCE THAT FACTOR IXA IS THE THROMBOGENIC TRIGGERIN PCC

Recent studies using assays for surrogate markers of thrombogenicity i n man have demonstrated that activation of the coagulation system occu rs following infusion of clinical doses of prothrombin complex concent rates (PCC) but not after the same doses of high-purity factor IX conc entrates (HP-FIX) in patients with haemophilia B. Here we have investi gated the mechanism of such thrombogenesis by applying assays that det ect early-through to late-events in coagulation system activation in a pharmacokinetic cross-over study of 50 IU/kg PCC and a new HP-FIX pro duct in haemophilia B patients. Satisfactory recoveries and half-lives were observed for both concentrates. HP-FIX caused no increases in th rombin-antithrombin III complex (TAT), prothrombin activation peptide fragment F-1+2 (F-1+2), factor X activation peptide (FXAP) or factor V IIa (FVIIa). In contrast the same dose of factor IX in the form of PCC was followed by significant increases over pre-infusion levels of TAT , F-1+2 and FXAP, but not FVIIa. Elevations of FIXAP occurred after bo th HP-FIX and PCC but did not reach normal levels and were attributed to normalisation of the FIX concentration in those patients whose leve ls of FIXAP were initially low. We conclude that the thrombogenic trig ger associated with PCC infusion occurs al the level of factor X activ ation. In the absence of any increase in FVIIa, we would attribute thi s to the likely presence of FIXa in the PCC.