Histopathological evaluation of thrombus in patients presenting with stent thrombosis. A multicenter European study: a report of the prevention of late stent thrombosis by an interdisciplinary global European effort consortium.

BACKGROUND: Stent thrombosis (ST) is a rare but serious complication following percutaneous coronary intervention. Analysis of thrombus composition from patients undergoing catheter thrombectomy may provide important insights into the pathological processes leading to thrombus formation. We performed a large-scale multicentre study to evaluate thrombus specimens in patients with ST across Europe. METHODS: Patients presenting with ST and undergoing thrombus aspiration were eligible for inclusion. Thrombus collection was performed according to a standardized protocol and specimens were analysed histologically at a core laboratory. Serial tissue cross sections were stained with haematoxylin-eosin (H&E), Carstairs and Luna. Immunohistochemistry was performed to identify leukocyte subsets, prothrombotic neutrophil extracellular traps (NETs), erythrocytes, platelets, and fibrinogen. RESULTS: Overall 253 thrombus specimens were analysed; 79 (31.2%) from patients presenting with early ST, 174 (68.8%) from late ST; 79 (31.2%) were from bare metal stents, 166 (65.6%) from drug-eluting stents, 8 (3.2%) were from stents of unknown type. Thrombus specimens displayed heterogeneous morphology with platelet-rich thrombus and fibrin/fibrinogen fragments most abundant; mean platelet coverage was 57% of thrombus area. Leukocyte infiltrations were hallmarks of both early and late ST (early: 2260 ± 1550 per mm(2) vs. late: 2485 ± 1778 per mm(2); P = 0.44); neutrophils represented the most prominent subset (early: 1364 ± 923 per mm(2) vs. late: 1428 ± 1023 per mm(2); P = 0.81). Leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction. Neutrophil extracellular traps were observed in 23% of samples. Eosinophils were present in all stent types, with higher numbers in patients with late ST in sirolimus-and everolimus-eluting stents. CONCLUSION: In a large-scale study of histological thrombus analysis from patients presenting with ST, thrombus specimens displayed heterogeneous morphology. Recruitment of leukocytes, particularly neutrophils, appears to be a hallmark of ST. The presence of NETs supports their pathophysiological relevance. Eosinophil recruitment suggests an allergic component to the process of ST.

Antithrombotic therapy in the anticoagulated patient undergoing percutaneous coronary intervention with coronary stenting.

PURPOSE OF REVIEW: Despite being the subject of extensive research, the optimal antithrombotic therapy for patients on chronic oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) with stent implantation is still unknown. This review presents the latest data regarding this much-debated topic. RECENT FINDINGS: Dual therapy, with clopidogrel (a P2Y12 inhibitor) and OAC, may be an alternative to triple therapy, which usually consists of aspirin and clopidogrel in addition to OAC, in terms of improving clinical outcomes in patients on chronic OAC following PCI with stent implantation. With the arrival of new, safer nonvitamin K antagonists oral anticoagulants (NOACs), the combination of NOAC and clopidogrel may also be an option for replacing triple therapy. In contrast to clopidogrel, combining the more potent P2Y12 inhibitors (prasugrel and ticagrelor) with OAC may only be considered in certain specific circumstances. SUMMARY: Patients on chronic OAC undergoing PCI with stent implantation require triple therapy. However, triple therapy is controversial, because it increases the risk of bleeding. With the introduction of prasugrel, ticagrelor and NOACs, the question arises which P2Y12 inhibitor to choose as part of the triple therapy regime and how NOACs combine with antiplatelet agents when treating patients undergoing PCI.