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Contractile forces in platelet aggregates under microfluidic shear gradients reflect platelet inhibition and bleeding risk.
- Source :
-
Nature communications [Nat Commun] 2019 Mar 13; Vol. 10 (1), pp. 1204. Date of Electronic Publication: 2019 Mar 13. - Publication Year :
- 2019
-
Abstract
- 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 α <subscript>IIb</subscript> β <subscript>3,</subscript> P2Y <subscript>12</subscript> , 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.
- Subjects :
- Adult
Aspirin pharmacology
Aspirin therapeutic use
Blood Coagulation drug effects
Blood Platelets drug effects
Computer Simulation
Cross-Sectional Studies
Drug Monitoring methods
Female
Hemorrhage etiology
Hemorrhage therapy
Humans
Male
Middle Aged
Myosins antagonists & inhibitors
Myosins metabolism
Platelet Aggregation drug effects
Platelet Aggregation Inhibitors therapeutic use
Platelet Glycoprotein GPIIb-IIIa Complex antagonists & inhibitors
Platelet Glycoprotein GPIIb-IIIa Complex metabolism
Platelet Glycoprotein GPIb-IX Complex antagonists & inhibitors
Platelet Glycoprotein GPIb-IX Complex metabolism
Prognosis
Thromboxane A2 metabolism
Wounds and Injuries blood
Wounds and Injuries therapy
Blood Platelets physiology
Hemorrhage diagnosis
Microfluidics methods
Platelet Aggregation physiology
Platelet Aggregation Inhibitors pharmacology
Wounds and Injuries complications
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 30867419
- Full Text :
- https://doi.org/10.1038/s41467-019-09150-9