BACKGROUND:Microparticles (MPs) have activity in thrombus promotion and generation. Erythrocyte microparticles (ErMPs) have been reported to accelerate fibrinolysis in the absence of permeation. We hypothesized that shear induced ErMPs would affect fibrin structure of clots and change flow with implications for fibrinolysis. OBJECTIVE:To determine effect of ErMPs on clot structure and fibrinolysis. METHODS:Plasma with elevated ErMPs was isolated from whole blood or washed red cells (RBCs) resuspended in platelet free plasma (PFP) after high shear. Dynamic light scattering (DLS) provided size distribution of ErMPs of sheared samples and unsheared PFP controls. Clots were formed by recalcification for flow/lysis experiments and examined by confocal microscopy and SEM. Flow rates through clots and time-to-lysis were recorded. A cellular automata model showed the effect of ErMPs on fibrin polymerization and clot structure. RESULTS:Coverage of fibrin increased by 41% in clots formed from plasma of sheared RBCs in PFP over controls. Flow rate decreased by 46.7% under a pressure gradient of 10 mmHg/cm with reduction in time to lysis from 5.7 ± 0.7 min to 12.2 ± 1.1 min (p < 0.01). Particle size of ErMPs from sheared samples (200 nm) was comparable to endogenous microparticles. CONCLUSIONS:ErMPs alter the fibrin network in a thrombus and affect hydraulic permeability resulting in decelerated delivery of fibrinolytic drugs.

中文翻译：

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剪切刺激的红细胞微粒：对凝块结构、流动和纤维蛋白溶解的影响

背景：微粒 (MPs) 在促进和生成血栓方面具有活性。据报道，红细胞微粒 (ErMP) 在没有渗透的情况下可加速纤维蛋白溶解。我们假设剪切诱导的 ErMPs 会影响凝块的纤维蛋白结构并改变流动，从而影响纤维蛋白溶解。目的：确定 ErMPs 对凝块结构和纤维蛋白溶解的影响。方法：从全血或经过高剪切后重悬于无血小板血浆 (PFP​​) 中的洗涤红细胞 (RBC) 中分离出 ErMP 升高的血浆。动态光散射 (DLS) 提供了剪切样品和未剪切 PFP 控件的 ErMP 的尺寸分布。通过用于流动/裂解实验的再钙化形成血块，并通过共聚焦显微镜和 SEM 检查。记录通过凝块的流速和裂解时间。细胞自动机模型显示了 ErMPs 对纤维蛋白聚合和凝块结构的影响。结果：与对照组相比，PFP 中剪切红细胞血浆形成的凝块中纤维蛋白的覆盖率增加了 41%。在 10 mmHg/cm 的压力梯度下，流速降低了 46.7%，裂解时间从 5.7 ± 0.7 分钟减少到 12.2 ± 1.1 分钟 (p < 0.01)。来自剪切样品 (200 nm) 的 ErMP 的粒径与内源性微粒相当。结论：ErMPs 改变血栓中的纤维蛋白网络并影响透水性，从而导致纤溶药物的递送减慢。7% 在 10 mmHg/cm 的压力梯度下，裂解时间从 5.7 ± 0.7 分钟减少到 12.2 ± 1.1 分钟 (p < 0.01)。来自剪切样品 (200 nm) 的 ErMP 的粒径与内源性微粒相当。结论：ErMPs 改变血栓中的纤维蛋白网络并影响透水性，从而导致纤溶药物的递送减慢。7% 在 10 mmHg/cm 的压力梯度下，裂解时间从 5.7 ± 0.7 分钟减少到 12.2 ± 1.1 分钟 (p < 0.01)。来自剪切样品 (200 nm) 的 ErMP 的粒径与内源性微粒相当。结论：ErMPs 改变血栓中的纤维蛋白网络并影响透水性，从而导致纤溶药物的递送减慢。