Minimal interference of concizumab with standard clinical coagulation laboratory assays – An in vitro study

Introduction Non‐factor replacement therapies are emerging as prophylactic treatment options in haemophilia A or B (HA/HB) with and without inhibitors. Concizumab is an anti‐tissue factor pathway inhibitor (TFPI) monoclonal antibody preventing factor (F)Xa inhibition and enhancing thrombin generation. Based on experience with other non‐factor therapies and extended half‐life products, there is a focus on potential interference with common clinical coagulation assays used to monitor patients treated with concizumab. Aim To evaluate the impact of concizumab on standard clinical coagulation assays. Methods Plasma samples (normal, HA/HB with/without inhibitors) in the presence/absence of added concizumab (250–16,000 ng/mL) were analysed in clinical assays including activated partial thromboplastin time (aPTT), prothrombin time (PT), FVIII and FIX one‐stage clot and chromogenic substrate assay, assays for detecting FVIII or FIX inhibitors and other assays for coagulation factors. Results Concizumab did not impact PT assays, but resulted in a small shortening of aPTT (up to 5 s in haemophilia plasma and 0.4 s in normal plasma). Concizumab had no, or only a minor impact on FVIII and FIX activity assays or Bethesda inhibitor assays. FXI and FXII activity in normal plasma, as measured by single factor aPTT‐based assay, was significantly increased in the presence of concizumab (+11% each). This was also the case for FVII and FX measured by PT‐based assays using plasma with 25% of FVII or FX (+64% and +22%, respectively). Conclusion The presence of concizumab did not, or only slightly, influence the outcome of standard clinical coagulation assays relevant for HA and HB.