Tutwiler Valerie, Peshkova Alina D, Andrianova Izabella A, Khasanova Dina R, Weisel John W, Litvinov Rustem I
From the Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia (V.T., J.W.W., R.I.L.); School of Biomedical Engineering, Sciences, and Health Systems, Drexel University, Philadelphia, PA (V.T.); Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia (A.D.P., I.A.A., R.I.L.); and Neurology Department, Interregional Clinical Diagnostic Center, Kazan, Russia (D.R.K.).
Arterioscler Thromb Vasc Biol. 2017 Feb;37(2):271-279. doi: 10.1161/ATVBAHA.116.308622. Epub 2016 Dec 1.
Obstructive thrombi or thrombotic emboli are the pathogenic basis of ischemic stroke. In vitro blood clots and in vivo thrombi can undergo platelet-driven contraction (retraction), resulting in volume shrinkage. Clot contraction can potentially reduce vessel occlusion and improve blood flow past emboli or thrombi. The aim of this work was to examine a potential pathogenic role of clot contraction in ischemic stroke.
We used a novel automated method that enabled us to quantify time of initiation and extent and rate of clot contraction in vitro. The main finding is that clot contraction from the blood of stroke patients was reduced compared with healthy subjects. Reduced clot contraction correlated with a lower platelet count and their dysfunction, higher levels of fibrinogen and hematocrit, leukocytosis, and other changes in blood composition that may affect platelet function and properties of blood clots. Platelets from stroke patents were spontaneously activated and displayed reduced responsiveness to additional stimulation. Clinical correlations with respect to severity and stroke pathogenesis suggest that the impaired clot contraction has the potential to be a pathogenic factor in ischemic stroke.
The changeable ability of clots and thrombi to shrink in volume may be a novel unappreciated mechanism that aggravates or alleviates the course and outcomes of ischemic stroke. The clinical importance of clot or thrombus transformations in vivo and the diagnostic and prognostic value of this blood test for clot contraction need further exploration.
阻塞性血栓或血栓性栓子是缺血性卒中的发病基础。体外血凝块和体内血栓可经历血小板驱动的收缩(回缩),导致体积缩小。凝块收缩可能会减少血管阻塞并改善通过栓子或血栓的血流。本研究旨在探讨凝块收缩在缺血性卒中中的潜在致病作用。
我们使用了一种新颖的自动化方法,能够在体外量化凝块收缩的起始时间、程度和速率。主要发现是,与健康受试者相比,卒中患者血液中的凝块收缩减少。凝块收缩减少与血小板计数降低及其功能障碍、纤维蛋白原和血细胞比容水平升高、白细胞增多以及其他可能影响血小板功能和血凝块特性的血液成分变化相关。卒中患者的血小板自发激活,对额外刺激的反应性降低。关于严重程度和卒中发病机制的临床相关性表明,凝块收缩受损有可能成为缺血性卒中的致病因素。
凝块和血栓体积缩小的可变能力可能是一种新的未被认识的机制,可加重或减轻缺血性卒中的病程和结局。体内凝块或血栓转变的临床重要性以及这种凝块收缩血液检测的诊断和预后价值需要进一步探索。