Abstract Number: PB0465
Meeting: ISTH 2021 Congress
Background: Inhibitor formation complicates hemophilia treatment and requires immune tolerance induction (ITI) to get rid of the high-titer inhibitors (> 5 BU/ml).
Aims: To assess the hemostatic response to FVIII replacement during ITI by studying thrombin generation (TG) related to traditional FVIII and inhibitor levels.
Methods: Seven hemophilia A patients undergoing ITI were studied. FVIII product was plasma-derived in one and recombinant in 6 patients with the dosing 100 IU/kg od. Patients underwent a laboratory assessment after 72-h wash-out period followed by a prospective observation of 12 months and a maximum of 36 months. TG by Genesia/STG-BleedScreen and inhibitor titers (BU/ml) by Nijmegen Bethesda assay were measured. FVIII and TG before and after FVIII infusions were periodically repeated during follow-up (at week 3, and at 3, 6 and 12 months). ABR (annual bleeding rate) and QoL (quality of life) were assessed.
Results: During the ITI, half of the patients achieved complete response within 6 months, one within 36 months, while two other patients achieved partial response. The peak inhibitor titer during ITI varied between 0.6 to 717 BU/mL (median 34). Genesia detected the hemostatic response to FVIII and ITI outcome. Post-infusion FVIII levels (30 min) correlated positively with ETP at week 3 (FVIII:C: r= 0.9 and p= 0.02; FVIII chromogenic: r=0.9 and p= 0.04), and both with peak thrombin (FVIII:C: r= 0.8 and p= 0.04; FVIII chromogenic: r=0.9 and p= 0.02) and ETP (FVIII:C: r= 0.9 and p= 0.03; FVIII chromogenic: r=0.8 and p= 0.04) at 6 months. In contrast, inhibitor titers correlated negatively with post-infusion peak height (r= -0.9 and p=0.02) and ETP (r=-0.9 and p=0.003) at 3 months, and lag time at 6 and 12 months (r=-0.9, p=0.03 and r=-0.9, p=0.01). ABR and QoL improved.
Conclusions: TG by Genesia distinguished different responses with a high sensitivity in inhibitor patients undergoing FVIII replacement.
To cite this abstract in AMA style:Szanto T, Lehtinen E, Lemponen M, Lassila R. Thrombin Generation by Genesia in Patients with Haemophilia A and Inhibitors during Immune Tolerance Induction [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/thrombin-generation-by-genesia-in-patients-with-haemophilia-a-and-inhibitors-during-immune-tolerance-induction/. Accessed November 29, 2023.
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