Lipinski Boguslaw, Pretorius Etheresia, Oberholzer Hester M, van der Spuy Wendy J
Harvard Medical School, Boston, Massachusetts, USA.
Ultrastruct Pathol. 2012 Apr;36(2):79-84. doi: 10.3109/01913123.2011.627491.
Activation of coagulation pathways results in the formation of hemostatic fibrin plugs. Under normal physiologic conditions fibrin clots are gradually, albeit completely, degraded by a fibrinolytic enzyme system to ensure proper wound healing and/or blood vessel patency. Yet in pathological situations, thrombi are not effectively removed, leading to chronic thrombosis. The susceptibility of blood clots to enzymatic degradation depends on the structure and properties of fibrin fibers. Many factors have been suspected as culprits, including red blood cells (RBCs) that become transiently trapped within fibrin mesh. Here, the authors show that there is indeed a specific interaction between RBCs and fibrin-like fibers identified here as dense matted deposits (DMDs) by means of scanning electron microscopy (SEM). It is emphasized that such interactions can be observed in ischemic stroke patients, but not from healthy subjects. However, DMD/RBC aggregates can be induced in normal blood by the additions of trivalent iron ions. The plausible mechanism of the enhanced fibrin-red blood cell interaction is based on the previously described iron-induced generation of hydroxyl radicals. These radicals cause, in turn, non-enzymatic formation of fibrinogen aggregates remarkably resistant to fibrinolysis that are also similar to DMDs described in this paper. In conclusion, this relatively simple SEM analysis may become a convenient tool for diagnosing prothrombotic conditions associated with iron overload. It is suggested that future research on prevention and treatment of ischemic stroke and other thrombosis associated diseases should include testing of iron-chelating and hydroxyl radical-scavenging agents.
凝血途径的激活导致止血性纤维蛋白凝块的形成。在正常生理条件下，纤维蛋白凝块会被纤维蛋白溶解酶系统逐渐（尽管是完全地）降解，以确保伤口正常愈合和/或血管通畅。然而，在病理情况下，血栓不能被有效清除，从而导致慢性血栓形成。血凝块对酶降解的敏感性取决于纤维蛋白纤维的结构和特性。许多因素被怀疑是罪魁祸首，包括暂时被困在纤维蛋白网内的红细胞（RBC）。在此，作者表明红细胞与本文通过扫描电子显微镜（SEM）鉴定为致密交织沉积物（DMD）的纤维蛋白样纤维之间确实存在特异性相互作用。需要强调的是，这种相互作用在缺血性中风患者中可以观察到，但在健康受试者中则不然。然而，通过添加三价铁离子可在正常血液中诱导形成DMD/RBC聚集体。纤维蛋白与红细胞相互作用增强的可能机制基于先前描述的铁诱导的羟基自由基生成。这些自由基反过来会导致纤维蛋白原聚集体的非酶形成，这种聚集体对纤维蛋白溶解具有显著抗性，且与本文所述的DMD相似。总之，这种相对简单的SEM分析可能成为诊断与铁过载相关的血栓前状态的便捷工具。建议未来对缺血性中风和其他血栓相关疾病的预防和治疗研究应包括对铁螯合剂和羟基自由基清除剂的测试。
