PlateChek: a surface-functionalized dielectric microsensor for specific detection of platelet-related hemostatic impairment in whole blood

BACKGROUND: Platelet count or function defects can result in hemostatic impairment, leading to life-threatening bleeding complications. While platelet transfusions are used to treat such complications, current clinical practice utilizes only platelet count thresholds to guide transfusion. This is because a single precision diagnostic system that can directly correlate both platelet count and function defects to hemostatic deficits is unavailable. OBJECTIVES: We developed PlateChek, a whole blood-based dielectric coagulometry microsensor that uses a gold electrode surface coated with a platelet-specific agonist, and tested the hypothesis that PlateChek can detect hemostatic impairment due to both platelet count and function defects. METHODS: PlateChek incorporates a gold electrode coated with thrombin receptor-activating peptide (TRAP)-6 to render clotting in a platelet-specific manner. Healthy blood was manipulated in vitro to recapitulate platelet count or function defects and tested in PlateChek to assess platelet-specific readout signatures. Finally, blood samples from patients with thrombocytopenia or platelet aggregation dysfunctions were used to validate PlateChek's ability to detect clinically relevant hemostatic impairment. RESULTS: In PlateChek, clotting kinetics were delayed in samples with platelet counts of < 50 k/μL compared to healthy controls and clot firmness was reduced with platelet counts of < 100 k/μL. PlateChek was sensitive to prolonged clotting time induced by vorapaxar inhibition and reduced clot firmness induced by tirofiban inhibition. PlateChek was sensitive to platelet counts of < 70 k/μL and platelet aggregation dysfunctions in clinical blood samples. CONCLUSION: PlateChek is a novel whole blood-based coagulometer with translational potential that directly correlates both platelet count and function defects to hemostatic impairment.