Oxidation Inhibits Iron-Induced Blood Coagulation

Abstract

Blood coagulation under physiological conditions is activated by thrombin, which converts soluble plasma fibrinogen (FBG) into an insoluble clot. The structure of the enzymatically-generated clot is very characteristic being composed of thick fibrin fibers susceptible to the fibrinolytic degradation. However, in chronic degenerative diseases, such as atherosclerosis, diabetes mellitus, cancer, and neurological disorders, fibrin clots are very different forming dense matted deposits (DMD) that are not effectively removed and thus create a condition known as thrombosis. We have recently shown that trivalent iron (ferric ions) generates hydroxyl radicals, which subsequently convert FBG into abnormal fibrin clots in the form of DMDs. A characteristic feature of DMDs is their remarkable and permanent resistance to the enzymatic degradation. Therefore, in order to prevent thrombotic incidences in the degenerative diseases it is essential to inhibit the iron-induced generation of hydroxyl radicals. This can be achieved by the pretreatment with a direct free radical scavenger (e.g. salicylate), and as shown in this paper by the treatment with oxidizing agents such as hydrogen peroxide, methylene blue, and sodium selenite. Although the actual mechanism of this phenomenon is not yet known, it is possible that hydroxyl radicals are neutralized by their conversion to the molecular oxygen and water, thus inhibiting the formation of dense matted fibrin deposits in human blood.

Acute induction of anomalous blood clotting by molecular amplification of highly substoichiometric levels of bacterial lipopolysaccharide (LPS)

“…thickness is much more heterogeneous after LPS is added; Clearly these tiny amounts of LPS are having enormous effects on the clotting process. These kinds of netted structures, that we have also termed 'dense matted deposits', were previously seen in inflammatory conditions such as diabetes [36][37][38], iron overload and stroke [36,[39][40][41]. Typically healthy fibrin fibre networks form a net where individual fibrin fibres are seen, but with added LPS a matted net develops.…”

Quantitative Assessment of Blood Coagulation by Cold Atmospheric Plasma

“…Our results suggest an important role for short-lived oxygen plasma species, such as the hydroxyl radical, in initiating blood coagulation. Reactive oxygen species, such as hydrogen peroxide and hydroxyl radical, 38,39 have been implicated in influencing the coagulation cascade via the activation of platelets. 40,41 It has been suggested that ROS cause clotting by inactivating anticoagulation agents that control clotting, such as endothelial-derived relaxing factor (EDRF), which counteracts platelet aggregation in vivo.…”

Prevention and follow-up in thromboembolic ischemic stroke: Do we need to think out of the box?

“…This approach is needed because stroke is a complicated disease with many factors contributing to the development of stroke, including metabolic syndrome and both acquired and non-acquired risk factors. The relation between iron, inflammation and hypercoagulability is well established [35][36][37][38] specifically the effect of iron on blood coagulation [39][40][41][42][43][44][45][46][47][48][49][50]. Changes to these structures might be used as -new‖ parameters in a screening protocol.…”