Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk
| Autor: | Nikita Taparia, Lucas H. Ting, Shirin Feghhi, Esther B. Lim, Nathan J. White, Annie O. Smith, Tessa Rue, Xu Wang, Nathan J. Sniadecki, Ari Karchin, Alex St. John |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Platelet Aggregation Thromboxane Microfluidics General Physics and Astronomy 02 engineering and technology Platelet inhibition P2Y12 Medicine Platelet lcsh:Science Aspirin Multidisciplinary biology Middle Aged 021001 nanoscience & nanotechnology Prognosis Platelet Glycoprotein GPIb-IX Complex Cardiology Female Drug Monitoring 0210 nano-technology medicine.drug Adult Blood Platelets medicine.medical_specialty Science Integrin Hemorrhage Platelet Glycoprotein GPIIb-IIIa Complex Myosins General Biochemistry Genetics and Molecular Biology Fibrin Article 03 medical and health sciences Thromboxane A2 Thrombin Internal medicine Humans Computer Simulation Blood Coagulation business.industry General Chemistry 030104 developmental biology Cross-Sectional Studies biology.protein Wounds and Injuries lcsh:Q business Platelet Aggregation Inhibitors |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-10 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-09150-9 |
| Popis: | Platelets contract forcefully after their activation, contributing to the strength and stability of platelet aggregates and fibrin clots during blood coagulation. Viscoelastic approaches can be used to assess platelet-induced clot strengthening, but they require thrombin and fibrin generation and are unable to measure platelet forces directly. Here, we report a rapid, microfluidic approach for measuring the contractile force of platelet aggregates for the detection of platelet dysfunction. We find that platelet forces are significantly reduced when blood samples are treated with inhibitors of myosin, GPIb-IX-V, integrin αIIbβ3, P2Y12, or thromboxane generation. Clinically, we find that platelet forces are measurably lower in cardiology patients taking aspirin. We also find that measuring platelet forces can identify Emergency Department trauma patients who subsequently require blood transfusions. Together, these findings indicate that microfluidic quantification of platelet forces may be a rapid and useful approach for monitoring both antiplatelet therapy and traumatic bleeding risk. Platelet aggregates generate contractile forces that contribute to their cohesion and adhesion. Here, Ting et al. develop a microfluidic device to measure contractile forces generated by platelet aggregates, and find it can detect the response of platelets to pharmacological agents and predict bleeding risk in trauma patients. |
| Databáze: | OpenAIRE |
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