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.