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

摘要

Abstract 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.