Debnath Maji1, Lalitha Nayak2, Janet Martin3, Ujjal D S Sekhon4, Anirban Sen Gupta4, Pedram Mohseni1, Michael A Suster1, Sanjay P Ahuja3. 1. Department of Electrical Engineering and Computer Science, Case Western Reserve University, Cleveland, Ohio. 2. Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, Ohio. 3. Division of Pediatric Hematology/Oncology, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio. 4. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.
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 Tpeak 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 Tpeak 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 Tpeak values was also noted at baseline among severe haemophilia A patients with inhibitors as compared to those without inhibitors. ClotChip Tpeak 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 Tpeak values correlate very well with ROTEM, TGA and FVIII assays, opening up possibilities for its use in personalized coagulation factor replacement therapy in haemophilia.
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 Tpeak 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 Tpeak 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 Tpeak values was also noted at baseline among severe haemophilia Apatients with inhibitors as compared to those without inhibitors. ClotChip Tpeak 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 Tpeak values correlate very well with ROTEM, TGA and FVIII assays, opening up possibilities for its use in personalized coagulation factor replacement therapy in haemophilia.
Authors: Amanda P Waller; Jonathan P Troost; Samir V Parikh; Katelyn J Wolfgang; Brad H Rovin; Marvin T Nieman; William E Smoyer; Matthias Kretzler; Bryce A Kerlin Journal: Thromb Res Date: 2021-02-16 Impact factor: 3.944
Authors: Yuncheng Man; Debnath Maji; Ran An; Sanjay P Ahuja; Jane A Little; Michael A Suster; Pedram Mohseni; Umut A Gurkan Journal: Lab Chip Date: 2021-03-05 Impact factor: 6.799