Monitoring once-weekly recombinant factor IX prophylaxis in hemophilia B with thrombin generation assay and factor IX activity

Introduction: Prophylaxis is the recommended treatment mode for severe hemophilia B. However, no single treatment regimen fits for all patients. Once-weekly prophylaxis with high-dose recombinant factor IX (rFIX) is efficacious, nevertheless, laboratory outcomes following 72 h after administration are lacking. Methods: In a prospective open-label noncomparative study, 10 severe/moderate (FIX <= 2 IU/dL) adult patients received rFIX dose (60100 IU/kg) after > 72 h washout on two occasions, separated by 7 days. We measured one-stage and chromogenic FIX, ROTEM, and thrombin generation (TG) assay in plasma after washout, 30 min after infusion, and at days 3, 4, and 7. Results: Median FIX clotting/chromogenic activity increased from 1.5/2.0 to 87/62 IU/dL following rFIX administration, chromogenic assay resulting in 30% lower recovery. Correspondingly TG was severely reduced at baseline and improved at recovery (peak thrombin 6.0 to 54 nM). Standard ROTEM failed to detect FIX deficiency. Both FIX activity and TG remained increased from days 3 to 7, with median trough levels of FIX clotting/chromogenic 3.0/3.0 IU/dL (>= 1 IU/dL in all severe patients) and peak thrombin 9.1 nM measured on day 7. FIX and TG assays were equally consistent between weeks 1 and 2. Conclusions: Once-weekly rFIX prophylaxis results in favorable laboratory outcome.