Fibrin Clot Formation under Oxidative Stress Conditions

Abstract

During coagulation, the soluble fibrinogen is converted into insoluble fibrin. Fibrinogen is a multifunctional plasma protein, which is essential for hemostasis. Various oxidative posttranslational modifications influence fibrinogen structure as well as interactions between various partners in the coagulation process. The aim was to examine the effects of oxidative stress conditions on fibrin clot formation in arterial atherothrombotic disorders. We studied the changes in in vitro fibrin network formation in three groups of patients—with acute coronary syndrome (ACS), with significant carotid artery stenosis (SCAS), and with acute ischemic stroke (AIS), as well as a control group. The level of oxidative stress marker malondialdehyde measured by LC-MS/MS was higher in SCAS and AIS patients compared with controls. Turbidic methods revealed a higher final optical density and a prolonged lysis time in the clots of these patients. Electron microscopy was used to visualize changes in the in vitro-formed fibrin network. Fibers from patients with AIS were significantly thicker in comparison with control and ACS fibers. The number of fibrin fibers in patients with AIS was significantly lower in comparison with ACS and control groups. Thus, oxidative stress-mediated changes in fibrin clot formation, structure and dissolution may affect the effectiveness of thrombolytic therapy.

Association of the Systemic Immune-Inflammation Index with Outcomes in Acute Coronary Syndrome Patients with Chronic Kidney Disease

“…32 The rupture of coronary atherosclerotic plaques and the formation of thrombi result in a blood flow blockade in an infarct-related artery area and are closely associated with acute coronary syndrome. 33 Inflammation is crucial to the initiation and progression of this process as well as its poor consequences. 34 Additionally, innate immunity and adaptive immunity are essential for atherosclerotic plaque rupture.…”

The Role of Oxidative Stress in Acute Ischemic Stroke-Related Thrombosis

“…From these results, it can be inferred that there is a close relationship between fibrinogen-bound 3-nitrotyrosine and stroke-related thrombosis, but the underlying mechanism remains elusive. A recent study further analyzed the influence of oxidative stress on fibrinogen function and fibrin network formation in patients with acute ischemic stroke [ 17 ]. The authors demonstrated that acute ischemic stroke patients showed a higher level of malondialdehyde, a marker of oxidative stress in vivo .…”

“…Moreover, they found that the final optical density of clots was higher and the lysis time of clots was prolonged in acute ischemic stroke patients. Interestingly, the clots from these patients exhibited thicker fibers but lower fibers number in comparison with the control group [ 17 ]. Consistent with this finding, exposure of fibrinogen to oxidative stress such as H 2 O 2 and NO in vitro also led to a similar change in the clot structure [ 115 , 116 ].…”

“…However, even after intravenous injection of rt-PA, the successful arterial recanalization rate is at a relatively low level (about 20-46%) [ 205 ]. As discussed previously, oxidative stress can affect fibrinogen function and fibrin network formation, leading to prolonged lysis time of clots [ 17 ]. Thus, we speculated that the combination of antioxidant stress therapy and rt-PA may be helpful for thrombolytic therapy.…”

“…Once initiated, oxidative stress can promote thrombus formation by inducing endothelial dysfunction, promoting platelet activation, facilitating platelet-leukocyte aggregation, and modifying fibrinogen function [13][14][15][16]. More importantly, oxidative stress has an impact on the maturation and stability of stroke-related thrombus, which might make it more difficult to be dissolved by conventional thrombolytic drugs and worsen the functional outcome of these patients [17]. Taken together, targeting oxidative stress might be a promising method for the prevention and thrombolytic treatment of stroke-related thrombus formation.…”