Platelet and Inflammatory Alterations Associated with Late Restenosis in Patients Undergoing Angioplasty and Brachytherapy.
Authors: Jeske Walter P. , Maszak Gary , Chawla Ravjyot , Cho Leslie , Lewis Bruce E. , Steen Lowell H. , Leya Ferdinand , Walenga Jeanine M. 
Published: October 2019

Restenosis limits long-term success of coronary angioplasty (PTCA). Intracoronary brachytherapy, while thought to provide a solution, has also been associated with late thrombotic occlusion. We hypothesized that platelets, with their associated hemostatic, immune modulatory, and inflammatory properties, are associated with these adverse reactions. Whole blood samples were collected from consented patients undergoing de novo PTCA with stent placement (n=57), or PTCA for stent restenosis followed by intracoronary β-radiation (n=18) or γ-radiation (n=22) at baseline (BL) and at 12-24 hrs, 4–6 wks, 6 months and 1 yr post-procedure. All patients were treated with heparin, a GPIIb/IIIa inhibitor, clopidogrel and aspirin prior to PTCA. Inflammatory activation was assessed in terms of plasma IL-6 and C-Reactive Protein (CRP) levels. Platelet activation was assessed in terms of platelet P-selectin expression and the formation of platelet-monocyte complexes using flow cytometry. A significant increase in the levels of platelet-monocyte complexes (β>de novo PTCA>γ) and IL-6 (β=γ>de novo stent) 12–24 hours post-PTCA has previously been shown while levels of P-selectin (+) platelets and CRP were not significantly different between the 3 groups at any time point [Circ. 106(19):II-621, 2002]. This patient population is now further analyzed in relation to the occurrence of restenosis during the 1-year post-procedure follow-up period. Clinical follow-up was available on 76 of 97 patients (78%).

Thirty-five of 76 patients exhibited some degree of late restenosis as detected by angiogram. The groups of patients with or without restenosis during the 1-year follow-up were evenly matched in terms of the incidence of diabetes (50% vs. 49%), hypertension (94% vs. 95%) and hyperlipidemia (85% vs. 90%). Patients experiencing restenosis during the follow-up period exhibited similar IL-6 levels as those patients who did not have restenosis. Although CRP levels were higher at BL and 12–24 hrs post-procedure in patients experiencing late restenosis (9.7±2.2 and 12.7±2.9 mg/ml, respectively) compared to patients without late restenosis (6.1±1.0 and 9.1±1.4 mg/ml, respectively), this difference did not reach statistical significance. Levels of platelet-monocyte complexes were increased relative to BL at 12–24 hours post-procedure (18.5±3.3% vs. 39.5±4.2%, p<0.05 vs. BL) in patients with restenosis at follow-up as well as in those without restenosis (15.5±2.4% vs. 39.4±3.5%, p<0.05 vs. BL).

Platelet activation, measured as the percentage of P-selectin (+) platelets, was higher in patients experiencing restenosis at follow-up (p<0.05 vs. no restenosis). At baseline and at 12-24 hours post-procedure, the percentage of activated platelets was approximately 2-fold higher in patients who would subsequently experience restenosis (BL: 1.7±0.4 vs. 0.7±0.1%; 12–24 hrs: 2.5±0.8 vs. 1.3±0.3%). While observed with all patients, this finding was more pronounced in de novo stent patients (BL: 2.1±0.1 vs. 0.8±0.2%; 12–24 hrs: 3.4±1.5 vs. 0.9±0.3%) compared to those receiving brachytherapy. Despite potent, multi-targeted anti-platelet therapy, significant post-procedural platelet activation was observed in patients undergoing PTCA with or without subsequent brachytherapy. The data suggest that enhanced platelet activation may contribute to the restenotic process. Whether the increased platelet activation observed in the restenotic patients is due to antiplatelet drug resistance remains to be determined.