Abstract Number: PB0819
Meeting: ISTH 2020 Congress
Background: Concizumab is a humanised, monoclonal antibody in phase 3 clinical development as a once-daily, subcutaneous prophylaxis for patients with haemophilia A and B with or without inhibitors. Concizumab specifically targets the Kunitz-2 domain of tissue factor pathway inhibitor (TFPI), blocking factor Xa binding to TFPI, thereby preventing tissue factor-FVIIa and FXa inhibition. During treatment of patients with haemophilia, physicians may need to measure haemostasic potential using activated partial thromboplastin time (aPTT), prothrombin time (PT) or FVIII or FIX activity assays using an aPTT-based one-stage clotting (OSC) or a chromogenic substrate (CS) assay. Thus, knowledge on whether concizumab affects these assays is imperative for optimal patient care.
Aims: To evaluate whether the presence of concizumab influences aPTT, PT, FVIII or FIX activity measurements.
Methods: Normal human plasma (NHP) treated with FVIII-neutralising antibody (to simulate inhibitors) or severe haemophilia A plasma were spiked with various concentrations of concizumab. aPTT and PT were measured on an ACL TOP®550 instrument using three different aPTT (SynthASil®, Actin® FS, STA®-Cephascreen) and PT (RecombiPlasTin 2G, Innovin®, PT HS PLUS) reagents. For FVIII or FIX activity determination, recombinant FVIII or FIX (NovoEight® or Benefix®) were spiked into severe haemophilia A or B plasma with or without 200 ng/mL concizumab and analysed using an OSC (SynthASil®) or a CS (BiophenFVIII:C or BiophenFIX) assay.
Results: No relevant interference by concizumab was observed in the aPTT or PT assays (Figure A-B). The presence of 200 ng/mL concizumab did not result in any statistically significant differences in factor activity measurements at any FVIII or FIX concentration using either an OSC or CS assay (Figure C-F).
Conclusions: Concizumab did not affect aPTT or PT measurements. Furthermore, concizumab did not affect FVIII or FIX activity measurements using either an OSC or CS assay.
To cite this abstract in AMA style:Kjalke M, Kjelgaard-Hansen M, Hilden I. Concizumab Does Not Affect Activated Partial Thromboplastin Time, Prothrombin Time or Factor VIII/IX Activity Measured Using One-Stage Clotting or Chromogenic Substrate Assays [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/concizumab-does-not-affect-activated-partial-thromboplastin-time-prothrombin-time-or-factor-viii-ix-activity-measured-using-one-stage-clotting-or-chromogenic-substrate-assays/. Accessed December 11, 2023.
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