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Assaying the efficacy of dual-antiplatelet therapy: use of a controlled-shear-rate microfluidic device with a well-defined collagen surface to track dynamic platelet adhesion.
- Source :
-
Analytical and bioanalytical chemistry [Anal Bioanal Chem] 2013 May; Vol. 405 (14), pp. 4823-34. Date of Electronic Publication: 2013 Mar 28. - Publication Year :
- 2013
-
Abstract
- We report the development and demonstration of an assay that distinguishes the pharmacological effects of two widely used antiplatelet therapies, aspirin (COX-1 inhibitor) and clopidogrel (P2Y12 inhibitor). Whole blood is perfused through a low-volume microfluidic device in contact with a well-characterized (ellipsometry, atomic force microscopy) acid-soluble type I collagen surface. Whole human blood treated in vitro with a P2Y12 inhibitor 2-methylthioadenosine 5'-monophosphate triethylammonium salt (2-MeSAMP) extended the time to the start of platelet recruitment, i.e., platelet binding to the collagen surface. Treatment with 2-MeSAMP also slowed the rate of aggregate buildup, with an overall reduced average platelet aggregate area after 8 min of constant blood flow. A far smaller effect was observed for in vitro treatment with aspirin, for which the rate of change of surface coverage is indistinguishable from controls. In whole blood obtained from patients under treatment with dual-antiplatelet therapy (aspirin and clopidogrel), a significant extension of time to platelet recruitment was observed along with a slowed rate of aggregate buildup and an average aggregate size approximately half that of control measurements. Differentiation of the pharmacological effects of these two well-targeted antiplatelet pathways suggests a role for this assay in determining the antiplatelet effects of these and related new therapeutics in clinical settings.
- Subjects :
- Blood Platelets drug effects
Cells, Cultured
Clopidogrel
Collagen chemistry
Dose-Response Relationship, Drug
Drug Combinations
Drug Evaluation, Preclinical instrumentation
Humans
Platelet Adhesiveness drug effects
Platelet Aggregation Inhibitors administration & dosage
Shear Strength
Surface Properties
Ticlopidine administration & dosage
Treatment Outcome
Aspirin administration & dosage
Biological Assay instrumentation
Blood Platelets physiology
Collagen pharmacokinetics
Flow Injection Analysis instrumentation
Platelet Adhesiveness physiology
Ticlopidine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1618-2650
- Volume :
- 405
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Analytical and bioanalytical chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23535745
- Full Text :
- https://doi.org/10.1007/s00216-013-6897-y