Sources of variability in platelet accumulation on type 1 fibrillar collagen in microfluidic flow assays.
Sources of variability in platelet accumulation on type 1 fibrillar collagen in microfluidic flow assays.
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DOI：
10.1371/journal.pone.0054680
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Di Paola JA
中科院分区：
文献类型：
--
作者：
Neeves KB;Onasoga AA;Hansen RR;Lilly JJ;Venckunaite D;Sumner MB;Irish AT;Brodsky G;Manco-Johnson MJ;Di Paola JA
微流体流动试验（MFA）测量剪切依赖性血小板功能在出血和血栓性疾病的诊断和治疗中具有潜在的临床应用。作为迈向临床应用的一步，本研究的目的是测量表型和遗传因素以及实验条件如何影响MFA内1型胶原蛋白上血小板积累的变异性。将全血以150、300、750和1500 s−1的壁剪切速率通过四个独立的通道（高50µm，宽500µm）灌注到1型纤维胶原蛋白上。血小板积累的特征包括血小板表面覆盖率1% （LagT）的滞后时间、血小板积累率（VPLT）和血小板表面覆盖率（SC）。对一组正常供体进行了检测，结果与血浆血管性血友病因子（VWF）水平、血小板计数、红细胞压积、性别和胶原蛋白受体基因型相关。VWF水平是血小板积累的最强决定因素。在所有壁面剪切速率下，VWF水平与VPLT和SC呈正相关。与静脉剪切速率相比，动脉剪切速率下血小板积累的LagT更长，这归因于血浆蛋白吸附到胶原蛋白所需的时间。血小板积累与血细胞比容或血小板计数之间没有关联。GP6基因的AG基因型个体在150 s−1和300 s−1时血小板积累低于AA基因型个体。与单独使用柠檬酸钠和玉米胰蛋白酶抑制剂（CTI）相比，再钙化的血液收集到柠檬酸钠和玉米胰蛋白酶抑制剂（CTI）中导致血小板积累减少，这表明柠檬酸盐不可逆地降低血小板功能。这项研究是健康供者MFA的最大关联研究（n = 104），可能为确定此类检测中血小板反应的正常范围奠定基础。
Microfluidic flow assays (MFA) that measure shear dependent platelet function have potential clinical applications in the diagnosis and treatment of bleeding and thrombotic disorders. As a step towards clinical application, the objective of this study was to measure how phenotypic and genetic factors, as well as experimental conditions, affect the variability of platelet accumulation on type 1 collagen within a MFA. Whole blood was perfused over type 1 fibrillar collagen at wall shear rates of 150, 300, 750 and 1500 s−1 through four independent channels with a height of 50 µm and a width of 500 µm. The accumulation of platelets was characterized by the lag time to 1% platelet surface coverage (LagT), the rate of platelet accumulation (VPLT), and platelet surface coverage (SC). A cohort of normal donors was tested and the results were correlated to plasma von Willebrand factor (VWF) levels, platelet count, hematocrit, sex, and collagen receptors genotypes. VWF levels were the strongest determinant of platelet accumulation. VWF levels were positively correlated to VPLT and SC at all wall shear rates. A longer LagT for platelet accumulation at arterial shear rates compared to venous shear rates was attributed to the time required for plasma proteins to adsorb to collagen. There was no association between platelet accumulation and hematocrit or platelet count. Individuals with the AG genotype of the GP6 gene had lower platelet accumulation than individuals with the AA genotype at 150 s−1 and 300 s−1. Recalcified blood collected into sodium citrate and corn trypsin inhibitor (CTI) resulted in diminished platelet accumulation compared to CTI alone, suggesting that citrate irreversibly diminishes platelet function. This study the largest association study of MFA in healthy donors (n = 104) and will likely set up the basis for the determination of the normal range of platelet responses in this type of assay.
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影响因子：
3.8
作者：
Conant, Carolyn G.;Schwartz, Michael A.;Nevill, J. Tanner
通讯作者：
Nevill, J. Tanner
DOI：
10.1161/atvbaha.111.242859
发表时间：
2012-08
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Fuchs TA;Brill A;Wagner DD
通讯作者：
Wagner DD
影响因子：
3.8
作者：
Hansen, Ryan R.;Wufsus, Adam R.;Barton, Steven T.;Onasoga, Abimbola A.;Johnson-Paben, Rebecca M.;Neeves, Keith B.
通讯作者：
Neeves, Keith B.
影响因子：
20.3
作者：
Flood, Veronica H.;Gill, Joan Cox;Montgomery, Robert R.
通讯作者：
Montgomery, Robert R.
影响因子：
10.4
作者：
Lisman, T;Adelmeijer, J;De Groott, PG
通讯作者：
De Groott, PG