Department of Physiology, Faculty of Health Sciences, University of Pretoria, Arcadia, South Africa.
Heart Lung Circ. 2013 Jun;22(6):447-9. doi: 10.1016/j.hlc.2012.10.010. Epub 2012 Dec 7.
The activation of blood coagulation leads to the formation of thrombin that, in turn, converts soluble plasma fibrinogen into insoluble fibrin clot. In healthy individuals, fibrin is effectively degraded; however, in prothrombotic states, proteolysis of fibrin clots are often delayed or even inhibited, and is associated with altered fibrin structure. We have previously shown that in inflammatory conditions like stroke and diabetes, this fibrin forms dense matted deposits. Although there are several factors that modify fibrin structure and delay fibrinolysis in these conditions, no mechanism is yet known to be responsible for a persistent presence of thrombi in the coronary and/or cerebral circulations. It seems, therefore, desirable to better understand this phenomenon in order to improve the effectiveness of thrombolytic therapies. Here, we show that ferric ions can activate non-enzymatic blood coagulation resulting in the formation of fibrin-like dense matted deposits (DMD) demonstrable by electron scanning microscopy (SEM). These DMDs are similar to those found in stroke and diabetes. On the basis of these findings we can conclude that the spontaneous formation of fibrin-like dense deposits in patients' blood may be a consequence of what is known as iron overload. Therefore, it is possible that inactivation of unbound iron in blood by small molecular weight chelating agents may prevent thrombotic consequences of the excessive accumulation of iron in the circulation.
血液凝固的激活导致凝血酶的形成，反过来又将可溶性血浆纤维蛋白原转化为不溶性纤维蛋白凝块。在健康个体中，纤维蛋白可被有效降解；然而，在血栓形成状态下，纤维蛋白凝块的蛋白水解常常被延迟甚至被抑制，并与纤维蛋白结构的改变有关。我们之前已经表明，在像中风和糖尿病这样的炎症情况下，这种纤维蛋白形成密集的缠结沉积物。尽管有几种因素可以改变这些情况下纤维蛋白的结构并延迟纤维蛋白溶解，但目前还不知道是什么机制导致冠状动脉和/或脑循环中血栓的持续存在。因此，为了提高溶栓治疗的效果，了解这种现象似乎是可取的。在这里，我们表明三价铁离子可以激活非酶促血液凝固，导致电子扫描显微镜（SEM）可检测到纤维蛋白样密集缠结沉积物（DMD）的形成。这些 DMD 类似于在中风和糖尿病中发现的。基于这些发现，我们可以得出结论，患者血液中纤维蛋白样密集沉积物的自发形成可能是所谓的铁过载的结果。因此，通过小分子螯合剂使血液中未结合的铁失活可能可以防止循环中铁过量积累引起的血栓形成后果。
