Kinetics of factor IX activity differ from that of factor IX antigen in patients with haemophilia B receiving high-purity factor IX replacement

Pharmacokinetic studies in haemophilia B have found in vivo recovery of FIX (FIX) to be uniformly lower than the factor VIII recovery in haemophilia A . We hypothesized that this lower recovery could result from rapid binding to high-affinity receptors on platelets and endothelium. To test this hypot hesis, we evaluated the kinetics of FIX activity and protein in haemophilia B patients. Twelve patients were enrolled in a double dosing, crossover st udy with two high-purity FIX concentrates, AlphaNine(R) SD and MonoNine(R). Subjects were given 40 U kg(-1) of FIX concentrate and blood samples were taken at 15, 30, and 60 min. A second infusion of 40 U kg(-1) was given aft er the 60 min blood sample and further blood samples removed at 15, 60, 120 , and 360 min after the second dose. Patients were infused with the alterna te concentrate at least 7 days later. Plasma samples were assayed for FIX a ctivity by coagulation assay and antigen by RIA. FIX antigen in the infused concentrates was measured and quantified as mu g U-1. There was no differe nce between the two FIX concentrates (AlphaNine(R) vs. MonoNine(R)) in the initial (15 min) activity (57% +/- 1 19% vs. 53% +/- 1 12%) and antigen (62 % +/- 1 16% vs. 55% +/- 1 19%) recoveries. Recoveries after the second FIX dose were not statistically different than those observed after the first F IX dose. In one patient, a doubling of the initial infusion dose did not in crease FIX recovery after the second FIX dose. However, the recovery of FIX antigen was significantly greater than the recovery of FIX activity and th e differences became more significant in the post-15 min samples. We calcul ated a ratio of plasma FIX antigen to FIX activity in mu g U-1. Average ant igen to activity ratio increased from 5.8 +/- 1 1.9 mu g U-1 at 15 min to 7 .1 +/- 1 2.2 mu g U-1 at 60 min. At 420 min the ratio increased to 9.3 +/- 1 2.4 mu g U-1. Although these studies failed to demonstrate a significant FIX receptor pool, they did demonstrate a phenomenon of progressive loss of biologic activity of the FIX protein after infusion of FIX concentrates.