Microfluidic Assay of Platelet Deposition on Collagen by Perfusion of Whole Blood from Healthy Individuals Taking Aspirin

被引:39
作者
Li, Ruizhi [1 ]
Fries, Susanne [2 ]
Li, Xuanwen [2 ]
Grosser, Tilo [2 ]
Diamond, Scott L. [1 ]
机构
[1] Univ Penn, Inst Med & Engn, Dept Chem & Biomol Engn, Philadelphia, PA 19104 USA
[2] Univ Penn, Perelman Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA
关键词
RESISTANCE; NONCOMPLIANCE; DISEASE;
D O I
10.1373/clinchem.2012.198101
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
BACKGROUND: Microfluidic devices can create hemodynamic conditions for platelet assays. We validated an 8-channel device in a study of interdonor response to acetylsalicylic acid (ASA, aspirin) with whole blood from 28 healthy individuals. METHODS: Platelet deposition was assessed before treatment or 24 h after ingestion of 325 mg ASA. Whole blood (plus 100 mu mol/L H-D-Phe-Pro-Arg-chloromethylketone to inhibit thrombin) was further treated ex vivo with ASA (0-500 mu mol/L) and perfused over fibrillar collagen for 300 s at a venous wall shear rate (200 s(-1)). RESULTS: Ex vivo ASA addition to blood drawn before aspirin ingestion caused a reduction in platelet deposition [half-maximal inhibitory concentration (IC50) approximately 10-20 mu mol/L], especially between 150 and 300 s of perfusion, when secondary aggregation mediated by thromboxane was expected. Twenty-seven of 28 individuals displayed smaller deposits (45% mean reduction; range 10%-90%; P < 0.001) from blood obtained 24 h after ASA ingestion (no ASA added ex vivo). In replicate tests, an R value to score secondary aggregation [deposition rate from 150 to 300 s normalized by rate from 60 to 150 s] showed R < 1 in only 2 of 28 individuals without ASA ingestion, with R < 1 in only 3 of 28 individuals after 500 mu mol/L ASA addition ex vivo. At 24 h after ASA ingestion, 21 of 28 individuals displayed poor secondary aggregation (R > 1) without ex vivo ASA addition, whereas the 7 individuals with residual secondary aggregation (R < 1) displayed insensitivity to ex vivo ASA addition. Platelet deposition was not correlated with platelet count. Ex vivo ASA addition caused similar inhibition at venous and arterial wall shear rates. CONCLUSIONS: Microfluidic devices quantified platelet deposition after ingestion or ex vivo addition of aspirin. (c) 2013 American Association for Clinical Chemistry
引用
收藏
页码:1195 / 1204
页数:10
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