Platelet Control of Fibrin Distribution and Microelasticity in Thrombus Formation Under Flow
Platelet Control of Fibrin Distribution and Microelasticity in Thrombus Formation Under Flow
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DOI：
10.1161/atvbaha.115.306537
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发表时间：
2016-04-01
影响因子：
8.7
通讯作者：
van der Meijden, Paola E. J.
中科院分区：
文献类型：
--
作者：
Swieringa, Frauke;Baaten, Constance C. F. M. J.;van der Meijden, Paola E. J.
目的血小板和纤维蛋白依赖性血栓的形成受血流量和胶原及组织因子的影响。然而，这些血液和血管成分之间的相互作用还没有很好地understood.Approach和Results在这里，我们开发了一种方法来评估全血血栓形成的微点与定义量的胶原蛋白和组织因子，允许确定的机械性能和intrathrombus组合物。限制胶原蛋白含量导致在高剪切流条件下血小板沉积和纤维蛋白形成减少，但这种影响通过较大的血栓尺寸和以基底区域为代价的血栓管腔区域中纤维蛋白积累增加来补偿。这些血栓更依赖于组织因子触发的凝血酶生成。微力纳米压痕分析显示，管腔定向纤维蛋白血栓的微弹性显着增加。在低剪切速率下，纤维蛋白纤维倾向于管腔覆盖血栓，再次导致更高的微弹性。对有不同止血不适应症患者血液的研究表明，在稀释性凝血病、血小板减少症、Scott综合征和血友病B病例中，血小板-纤维蛋白血栓的形成受到损害。（3）血小板粘附的限制使纤维蛋白从血栓的底部重定向到顶部;（4）较低的剪切速率促进纤维蛋白覆盖血栓;（5）纤维蛋白分布模式决定血栓微弹性;（6）在具有不同止血缺陷的患者中，血栓形成过程减少。
Objective Platelet- and fibrin-dependent thrombus formation is regulated by blood flow and exposure of collagen and tissue factor. However, interactions between these blood-borne and vascular components are not well understood.Approach and Results Here, we developed a method to assess whole-blood thrombus formation on microspots with defined amounts of collagen and tissue factor, allowing determination of the mechanical properties and intrathrombus composition. Confining the collagen content resulted in diminished platelet deposition and fibrin formation at high shear flow conditions, but this effect was compensated by a larger thrombus size and increased accumulation of fibrin in the luminal regions of the thrombi at the expense of the base regions. These thrombi were more dependent on tissue factor-triggered thrombin generation. Microforce nanoindentation analysis revealed a significantly increased microelasticity of thrombi with luminal-oriented fibrin. At a low shear rate, fibrin fibers tended to luminally cover the thrombi, again resulting in a higher microelasticity. Studies with blood from patients with distinct hemostatic insufficiencies indicated an impairment in the formation of a platelet-fibrin thrombus in the cases of dilutional coagulopathy, thrombocytopenia, Scott syndrome, and hemophilia B.Conclusions Taken together, our data indicate that (1) thrombin increases the platelet thrombus volume; (2) tissue factor drives the formation of fibrin outside of the platelet thrombus; (3) limitation of platelet adhesion redirects fibrin from bottom to top of the thrombus; (4) a lower shear rate promotes thrombus coverage with fibrin; (5) the fibrin distribution pattern determines thrombus microelasticity; and (6) the thrombus-forming process is reduced in patients with diverse hemostatic defects.