In Vitro Assessment of Nanoparticle Effects on Blood Coagulation
In Vitro Assessment of Nanoparticle Effects on Blood Coagulation
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DOI：
10.1007/978-1-4939-7352-1_10
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发表时间：
2018-01-01
期刊：
影响因子：
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通讯作者：
Dobrovolskaia, Marina A.
中科院分区：
文献类型：
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作者：
Potter, Timothy M.;Rodriguez, Jamie C.;Dobrovolskaia, Marina A.
血液凝固是一个复杂的过程，涉及细胞和生化成分。在血液凝固过程中起关键作用的细胞是血小板。其他细胞，包括白细胞和内皮细胞，通过在其表面表达所谓的促凝血活性（PCA）复合物来促进凝血。凝血的生化成分由血浆凝血级联反应表示，其中包括血浆蛋白，也称为凝血因子。血小板、白细胞、内皮细胞和血浆凝血因子之间的协调相互作用对于维持止血和防止过度出血是必要的。所有或部分这些成分的不良激活可能导致病理性凝血和危及生命的情况，如消耗性凝血病或弥散性血管内凝血（DIC）。相反，凝血途径的意外抑制可能导致出血。致血栓性是测试材料通过影响凝血过程中的一个或多个元素来诱导血液凝固的特性。抗凝活性是指测试材料抑制凝血的性能。引起血小板聚集、扰乱血浆凝血和诱导白细胞PCA的倾向可以作为纳米材料在体内促凝或抗凝可能性的体外测量。本章描述了体外分析血小板聚集、血浆凝固时间和白细胞PCA激活的三个步骤。血小板聚集和血浆凝固程序已在前面介绍过。这里的修订包括有关纳米颗粒样品制备的更新细节，纳米颗粒浓度的选择体外研究，并更新了有关分析控制的细节。本章扩展到描述白细胞PCA分析的方法和案例研究，展示了这些体外分析的性能。
Blood clotting is a complex process which involves both cellular and biochemical components. The key cellular players in the blood clotting process are thrombocytes or platelets. Other cells, including leukocytes and endothelial cells, contribute to clotting by expressing the so-called pro-coagulant activity (PCA) complex on their surface. The biochemical component of blood clotting is represented by the plasma coagulation cascade, which includes plasma proteins also known as coagulation factors. The coordinated interaction between platelets, leukocytes, endothelial cells, and plasma coagulation factors is necessary for maintaining hemostasis and for preventing excessive bleeding. Undesirable activation of all or some of these components may lead to pathological blood coagulation and life-threatening conditions such as consumptive coagulopathy or disseminated intravascular coagulation (DIC). In contrast, unintended inhibition of the coagulation pathways may lead to hemorrhage. Thrombogenicity is the property of a test material to induce blood coagulation by affecting one or more elements of the clotting process. Anticoagulant activity refers to the property of a test material to inhibit coagulation. The tendency to cause platelet aggregation, perturb plasma coagulation, and induce leukocyte PCA can serve as an in vitro measure of a nanomaterial's likelihood to be pro- or anticoagulant in vivo. This chapter describes three procedures for in vitro analyses of platelet aggregation, plasma coagulation time, and activation of leukocyte PCA. Platelet aggregation and plasma coagulation procedures have been described earlier. The revision here includes updated details about nanoparticle sample preparation, selection of nanoparticle concentration for the in vitro study, and updated details about assay controls. The chapter is expanded to describe a method for the leukocyte PCA analysis and case studies demonstrating the performance of these in vitro assays.