title: The hypercoagulable profile of patients with stent thrombosis.
abstract: OBJECTIVE
  Coronary stent thrombosis is a devastating complication after percutaneous coronary intervention (PCI). The mechanisms underlying stent thrombosis are multifactorial. Whether the coagulation system is involved in the pathophysiology of stent thrombosis is unclear. We hypothesised that thrombin generation, reflecting the coagulation potential, is enhanced in patients with stent thrombosis.
  
  
  METHODS
  A case-control study was performed, including 63 patients with PCI: 23 cases (stent thrombosis) and 40 controls (no stent thrombosis). Thrombin generation was measured using 0, 1 and 5 pM tissue factor (TF) triggers. Active site-inhibited factor VIIa (ASIS) and recombinant thrombomodulin were added to study the contact activation system and the protein C pathway, respectively.
  
  
  RESULTS
  Thrombin generation was significantly increased for all TF triggers in cases compared with controls. Addition of ASIS to the measurement without exogenous TF revealed significantly enhanced contact activation in cases compared with controls; mean peak height: 241 vs 183 nM. Thrombin generation was also significantly increased in cases compared with controls in the presence of exogenous TF; mean peak height: 263 vs 233 nM (5 pM TF). Addition of thrombomodulin reduced thrombin generation by 23% in cases and 31% in controls (p<0.018), suggesting alterations in the protein C pathway in cases.
  
  
  CONCLUSIONS
  This is the first study that suggests the involvement of the coagulation system in stent thrombosis. Stent thrombosis patients showed a hypercoagulable state, most likely caused by enhanced contact activation and attenuation of anticoagulation by the protein C pathway.
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Departments of Internal Medicine and Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Loeffen
authors.affiliation: Department of Cardiology, St. Antonius Center for Platelet Function Research, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: T C
authors.initials: TC
authors.lastname: Godschalk
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Departments of Internal Medicine and Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van Oerle
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Departments of Internal Medicine and Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: H M H
authors.initials: HM
authors.lastname: Spronk
authors.affiliation: Department of Clinical Chemistry, St. Antonius Center for Platelet Function Research, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Hackeng
authors.affiliation: Department of Cardiology, St. Antonius Center for Platelet Function Research, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: ten Berg
authors.affiliation: Laboratory for Clinical Thrombosis and Haemostasis, Departments of Internal Medicine and Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: ten Cate
mesh_terms: D000368:Aged; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D003328:Coronary Thrombosis / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects* / Q000295:instrumentation*; D011237:Predictive Value of Tests; D011486:Protein C / Q000378:metabolism; D012307:Risk Factors; D015607:Stents; D013917:Thrombin / Q000378:metabolism; D019851:Thrombophilia / Q000097:blood / Q000150:complications*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011486:Protein C; D013917:Thrombin