The mechanism of stent restenosis is unclear. Neointimal hyperplasia remains the primary mechanism of restenosis. Platelets play an important role in the process of vascular neointimal hyperplasia [7–10]. Studies have reported that superficial femoral artery ISR occurs within approximately 18—40 percent of patients undergoing stenting within one year . In our study, the one year restenosis rate of the superficial femoral artery stent was 19.6 percent, which was consistent with other research findings.
Our study observed that in patients presenting with restenosis within 12 months, the MPV increased after stent implantation. Norgaz et al.  reported that a pre-operative MPV > 8.4 fL was associated with restenosis within six months after coronary stent implantation and there was a positive correlation between a preoperative MPV and the occurrence of ISR (r = 0.44; P<0.001). However, the relationship between post-operative platelet volume and stent restenosis has not been analyzed. Dai et al.  reported that a pre-operative MPV of more than 10.1 fL was associated with restenosis within 16 months after carotid stent implantation (P = 0.013). There was no significant difference between the pre- and post-operative MPV in CAS patients.
We observed that the pre-operative MPV in the ISR group was 8.49 ± 0.91 fL compared to 8.31 ± 0.82 fL in the no-restenosis group (P>0.05); however, the post-operative MPV in the ISR group was 10.04 ± 0.68 fl as compared to 9.11 ± 0.79 fl in the no-restenosis group (P<0.001). There was no correlation between the pre-operative MPV and an occurrence of ISR (r = 0.11; P>0.05). However, we did find a positive correlation between the post-operative MPV and an occurrence of ISR (r = 0.58; P<0.001). Patients with an MPVD of not less than 1.5fL had a 11.79-fold higher risk of ISR when compared with an MPVD of less than 1.5 fL. Moreover, patients with an MPVDR of not less than 17.9 percent had a 10.72-fold higher risk of ISR than did patients with an MPVDR of less than 17.9 percent. Further, Hu et al.  reported that patients with a higher platelet distribution width, defined as more than 13.65 percent, had a four-fold higher risk of ISR as compared with a lower platelet distribution width after coronary stent implantation.
Our study found no correlation between the platelet distribution width and an occurrence of ISR. These discrepancies might be caused by the different lesion sites studied. The superficial femoral artery stent might be affected by the compression, pulling and torsion of the thigh muscle, while the coronary and carotid arteries are less affected by the muscle. In addition, the blood flow velocity differs among that seen for the superficial femoral artery and the coronary and carotid arteries. We found that changes in the MPV for patients with restenosis have a negative linear relationship with the onset time of restenosis. It is suggested that the greater the change in the MPV during pre- and post-operative superficial femoral artery stent implantation, the shorter the onset time of restenosis. In addition, our study observed an increase in MPV and a decrease in platelet count in patients with restenosis.
Inoue et al.  reported 48 patients with left anterior descending coronary artery disease that were randomly assigned to either a balloon angioplasty group or a coronary stent group. The heparin-coated catheter remained in the coronary sinus for 48 hours after the procedure. Coronary sinus blood and peripheral blood were obtained, before, immediately after, and at 24 and 48 hours after the procedure. By flow cytometric analysis, it was demonstrated that in the coronary sinus of the stent group, the expression of platelet CD62P increased significantly, and did so immediately after the procedure, and these trends continued during the 48-hour observation period. By contrast, in the coronary sinus of the balloon group, the expression of platelet CD62P increased less significantly when measured immediately after the procedure, and declined to baseline levels 24 hours after the procedure. This result suggested that platelet activation that occurs in the coronary circulation after coronary stenting was both stronger and more persistent than following the balloon angioplasty procedure. Platelets do not have any nuclei, and their size and α-granule content are controlled by megakaryocyte development and differentiation .
In one particular animal study, Martin et al.  reported observations from a rabbit model following the intravenous daily injection of anti-rabbit platelet serum for six continuous days. At the end of the six day period, multiple fragments of bone marrow from the femoral shafts were taken. Megakaryocyte were measured using a Kontron MOP AM03 system. It was shown that the volume of megakaryocyte cytoplasm significantly increased and stimulated platelet production. The platelet volume produced per megakaryocyte also increased. Large platelets contain more α-granules. Moreover, platelet α-granules contain PDGF, which is thought to be the most potent mitogen in the process of smooth muscle cell hyperplasia, and the occurrence of neointimal hyperplasia .
Inoue et al.  measured serum levels of glycosyl-phosphatidil-inositol-anchored-protein–80, which is a modulator of Mac–1 on the surface of neutrophils in patients that had undergone coronary stent implantation. This group reported activation of neutrophils and neutrophil-mediated oxidative burst in the inflammatory process of PCI-induced vessel injury and neointimal hyperplasia. Chang et al.  recruited 180 patients and obtained venous blood samples one to three days before superficial femoral artery stent implantation. The neutrophil-lymphocyte ratio was computed using the absolute neutrophil count divided by the absolute lymphocyte count. This group observed that the neutrophil-lymphocyte ratio was significantly higher in the early ISR (i.e., within one year) group than that seen in the non-ISR group. The neutrophil-lymphocyte ratio that was not less than 3.62, was independently and positively associated with a higher risk of early ISR after stent implantation in patients with femoro-popliteal chronic total occlusion.
However, we found that the neutrophil-lymphocyte ratio was negatively correlated with ISR. This discrepancy is likely due to the patients in our study that did not have severe limb ischemia. However, Verdoia et al.  reported that in patients undergoing coronary angiography, the neutrophil-lymphocyte ratio is independently associated with ISR. In a study using coronary arteries of swine, Nakatani et al.  reported that neointimal hyperplasia after stenting lasts longer than is seen following balloon injury, presumably due to the inflammatory cells that are found around the stent struts. Inflammatory cells, such as macrophages and eosinophils, are intimately linked to the differences seen in neointimal hyperplasia following balloon injury as compared stenting. We found that post-operative cell counts of neutrophils, leukocytes, eosinophils, and basophils were all higher than was found preoperatively.
There are several limitations in the present study. First, this study was conducted on a retrospective basis, like other studies, represented a single center experience. Second, the limitations of our study was the small sample, which we recognize might lead to differences in some of the reported observations. Thied, the predictive effect of the serum inflammatory factor concentrations on restenosis after stent implantation was also neglected, which we recognize will need to be confirmed by further studies. In addition, although there are many factors (procedure related factor, underlying vascular disease factor, etc) which can affect in-stent restenosis (ISR), these factors were not fully evaluated in this study.