Abstract 13819: The Hypercoagulable Profile of Stent Thrombosis Patients
Introduction: Stent thrombosis (ST) is a devastating complication after percutaneous coronary intervention (PCI), with major clinical impact due to the high risk of myocardial infarction and death, as well as a high recurrence rate. A low degree of platelet inhibition is a risk factor for ST, but the contribution of the coagulation system in the pathophysiology of ST is unexplored. We hypothesized that thrombin generation (TG), reflecting the coagulation potential, is enhanced in ST patients.
Methods: A case-control study was performed including cases (n=23) with a history of an angiographically confirmed ST during follow-up and controls (n=40) with a previously implanted stent but no ST ≥12 months after index PCI. Time between index PCI (controls) or ST PCI (cases) and blood collection was ≥3 months. Coagulation activity was assessed by D-dimer and thrombin-antithrombin (TAT) levels. TG was analyzed with 0, 1, and 5 pM tissue factor (TF) triggers.
Results: D-dimer and TAT levels were not significantly different between cases and controls. However, TG was significantly increased in cases compared to controls in the absence of an exogenous TF stimulus and in the presence of an extrinsic pathway inhibitor; peak height: 241 vs. 183 nM, velocity index: 98 vs. 63 nM/min, respectively; all P<0.05. Overall, TG triggered with 1 or 5 pM TF was significantly enhanced in cases compared to controls. The endogenous thrombin potential in the presence of thrombomodulin was reduced by 23% in cases and 31% in controls (P<0.05), suggesting diminished activation of the protein C pathway in ST patients. Logistic regression analysis revealed an increased TG to be predictive for ST development, with ORs for patients in the lowest quartile vs. the highest of 9.9 (95%CI 2.8-35.0) and 36.7 (95%CI 4.5-300.6), respectively for time to peak and time to tail (0 pM TF in presence of an extrinsic pathway inhibitor).
Conclusions: This is the first study demonstrating the involvement of the plasma coagulation system in ST. Patients with a history of ST showed a shift towards a hypercoagulable state, most likely caused by enhanced contact activation and attenuation of anticoagulation by the protein C pathway. These findings may eventually influence antithrombotic management in patients at risk of ST.
- © 2013 by American Heart Association, Inc.