A novel, point-of-care, whole-blood assay utilizing dielectric spectroscopy is sensitive to coagulation factor replacement therapy in haemophilia A patients

Background: Reliable monitoring of coagulation factor replacement therapy in patients with severe haemophilia, especially those with inhibitors, is an unmet clinical need. While useful, global assays, eg thromboelastography (TEG), rotational thromboelastometry (ROTEM) and thrombin generation assay (TGA), are cumbersome to use and not widely available.

Objective: To assess the utility of a novel, point-of-care, dielectric microsensor - ClotChip - to monitor coagulation factor replacement therapy in patients with haemophilia A, with and without inhibitors.

Methods: The ClotChip T_peak parameter was assessed using whole-blood samples from children with severe haemophilia A, with (n = 6) and without (n = 12) inhibitors, collected pre- and postcoagulation factor replacement therapy. ROTEM, TGA and chromogenic FVIII assays were also performed. Healthy children (n = 50) served as controls.

Results: ClotChip T_peak values exhibited a significant decrease for samples collected postcoagulation factor replacement therapy as compared to baseline (pretherapy) samples in patients with and without inhibitors. A difference in T_peak values was also noted at baseline among severe haemophilia A patients with inhibitors as compared to those without inhibitors. ClotChip T_peak parameter exhibited a very strong correlation with clotting time (CT) of ROTEM, endogenous thrombin potential (ETP) and peak thrombin of TGA, and FVIII clotting activity.

Conclusions: ClotChip is sensitive to coagulation factor replacement therapy in patients with severe haemophilia A, with and without inhibitors. ClotChip T_peak values correlate very well with ROTEM, TGA and FVIII assays, opening up possibilities for its use in personalized coagulation factor replacement therapy in haemophilia.