Department of Mechanical Engineering, University of California, Berkeley, CA, USA.
Department of Chemical and Biomolecular Engineering, Institute for Medicine and Engineering, Philadelphia, PA, USA.
J Thromb Haemost. 2018 May;16(5):973-983. doi: 10.1111/jth.13986. Epub 2018 Apr 2.
Essentials Platelet packing density in a hemostatic plug limits molecular movement to diffusion. A diffusion-dependent steep thrombin gradient forms radiating outwards from the injury site. Clot retraction affects the steepness of the gradient by increasing platelet packing density. Together, these effects promote hemostatic plug core formation and inhibit unnecessary growth.
Background Hemostasis studies performed in vivo have shown that hemostatic plugs formed after penetrating injuries are characterized by a core of highly activated, densely packed platelets near the injury site, covered by a shell of less activated and loosely packed platelets. Thrombin production occurs near the injury site, further activating platelets and starting the process of platelet mass retraction. Tightening of interplatelet gaps may then prevent the escape and exchange of solutes. Objectives To reconstruct the hemostatic plug macro- and micro-architecture and examine how platelet mass contraction regulates solute transport and solute concentration in the gaps between platelets. Methods Our approach consisted of three parts. First, platelet aggregates formed in vitro under flow were analyzed using scanning electron microscopy to extract data on porosity and gap size distribution. Second, a three-dimensional (3-D) model was constructed with features matching the platelet aggregates formed in vitro. Finally, the 3-D model was integrated with volume and morphology measurements of hemostatic plugs formed in vivo to determine how solutes move within the platelet plug microenvironment. Results The results show that the hemostatic mass is characterized by extremely narrow gaps, porosity values even smaller than previously estimated and stagnant plasma velocity. Importantly, the concentration of a chemical species released within the platelet mass increases as the gaps between platelets shrink. Conclusions Platelet mass retraction provides a physical mechanism to establish steep chemical concentration gradients that determine the extent of platelet activation and account for the core-and-shell architecture observed in vivo.
止血塞中血小板的堆积密度限制了分子的扩散运动。扩散依赖的陡梯度凝血酶从损伤部位向外辐射形成。血小板堆积密度的增加会影响梯度的陡度。这些效应共同促进了止血塞核心的形成，并抑制了不必要的生长。
背景在体内进行的止血研究表明，穿透性损伤后形成的止血塞的特征是靠近损伤部位的高度激活、紧密堆积的血小板核心，覆盖着较少激活和松散堆积的血小板外壳。凝血酶在损伤部位附近产生，进一步激活血小板并开始血小板质量回缩的过程。然后，血小板之间的间隙变紧可能会阻止溶质的逸出和交换。目的重建止血塞的宏观和微观结构，并研究血小板质量收缩如何调节血小板之间间隙中的溶质运输和溶质浓度。方法我们的方法包括三个部分。首先，使用扫描电子显微镜分析在流动条件下体外形成的血小板聚集物，以提取有关孔隙率和间隙尺寸分布的数据。其次，构建了一个具有与体外形成的血小板聚集物相匹配的特征的三维（3-D）模型。最后，将 3-D 模型与体内形成的止血塞的体积和形态测量相结合，以确定溶质如何在血小板塞微环境中移动。结果结果表明，止血塞的特征是极其狭窄的间隙，孔隙率值甚至比以前估计的还要小，并且血浆速度停滞。重要的是，在血小板质量内释放的化学物质的浓度随着血小板之间间隙的缩小而增加。结论血小板质量收缩提供了一种物理机制，可以建立陡峭的化学浓度梯度，从而决定血小板的激活程度，并解释在体内观察到的核心-壳结构。
