Sakariassen K S, Barstad R M
Biotechnology Centre of Oslo, University of Oslo, Norway.
Blood Coagul Fibrinolysis. 1993 Aug;4(4):615-25. doi: 10.1097/00001721-199308000-00013.
Thrombus formation at a ruptured arterial plaque forming a stenotic luminal outgrowth may trigger acute vascular occlusion. The pathobiology of the complex mechanisms and their interrelationships during this event is not fully understood. However, it is generally believed that components of the subendothelial plaque and the disturbed blood flow conditions caused by the stenosis are of pivotal importance for the thrombus formation. The shape and the severity of the occluding stenosis have profound impacts on the physical aspects of the blood flow. The wall shear rate at the apex may reach extremely high values (> 40,000 s-1). Zones of recirculation proximal and distal to the stenosis as well as turbulent blood flow further downstream from the lesion may occur. The significance of these rheological factors for the mural thrombus formation at various locations at the stenosis is not well established. The extracellular matrix and the cellular components of the subendothelial plaque exposed to the blood stream following plaque rupture are potent inducers of thrombus formation. Matrix components such as collagen fibrils, fibronectin and von Willebrand factor interact specifically with platelet membrane glycoprotein receptors, Ia-IIa, Ib-IX, and IIB-IIa, enabling platelet-subendothelium adhesion, particularly at high wall shear rates. The coagulation cascade is concomitantly activated by the binding of FVII from plasma to tissue factor expressed on the membranes of macrophages and smooth muscle cells. Thrombin, which is subsequently generated at the rupture, enhances the platelet recruitment, and thus the thrombus growth. The thrombin formation simultaneously enhances the deposition of fibrin in and around the platelet masses. Further augmentation of these processes is mediated by the formation of prothrombinase complexes on the phospholipid-rich surfaces of the activated platelets, which increases the local concentration of thrombin at the evolving thrombus. Thrombus fragmentation may represent a serious event, since these fragments may embolize and occlude smaller vessels, producing ischaemia. It is apparent that acute arterial thrombotic occlusion triggered by a ruptured stenotic plaque involves both physical and chemical mechanisms. The inter-relationship and the significance of these complex mechanisms are not well understood. Efficient modalities for therapeutic intervention in thromboembolism at such lesions may not be available before the physical and chemical events are better identified and characterized.
动脉斑块破裂处形成狭窄的管腔突出物时血栓形成，可能引发急性血管闭塞。在此过程中，复杂机制及其相互关系的病理生物学尚未完全明确。然而，一般认为内皮下斑块的成分以及狭窄导致的血流紊乱状况对于血栓形成至关重要。闭塞性狭窄的形状和严重程度对血流的物理特性有深远影响。狭窄顶端的壁面剪切速率可能达到极高值（>40,000 s-1）。狭窄近端和远端可能出现再循环区域，病变下游更远端可能出现湍流。这些流变学因素在狭窄处不同位置对壁血栓形成的意义尚未明确。斑块破裂后暴露于血流中的内皮下斑块的细胞外基质和细胞成分是血栓形成的有力诱导剂。诸如胶原纤维、纤连蛋白和血管性血友病因子等基质成分与血小板膜糖蛋白受体Ia-IIa、Ib-IX和IIB-IIa特异性相互作用，使血小板与内皮下黏附，尤其是在高壁面剪切速率时。血浆中的FVII与巨噬细胞和平滑肌细胞膜上表达的组织因子结合，同时激活凝血级联反应。随后在破裂处产生的凝血酶增强血小板募集，进而促进血栓生长。凝血酶形成同时增强纤维蛋白在血小板团块内及周围的沉积。这些过程的进一步增强由活化血小板富含磷脂的表面上凝血酶原酶复合物的形成介导，这增加了正在形成的血栓处凝血酶的局部浓度。血栓破碎可能是严重事件，因为这些碎片可能栓塞并阻塞较小血管，导致缺血。显然，由破裂的狭窄斑块引发的急性动脉血栓闭塞涉及物理和化学机制。这些复杂机制的相互关系和意义尚未完全明了。在更好地识别和表征物理和化学事件之前，可能无法获得针对此类病变血栓栓塞的有效治疗手段。
