title: Increased responsiveness to thrombin through protease-activated receptors (PAR)-1 and -4 in active Crohn's disease.
abstract: OBJECTIVE
  Platelets are essential in hemostasis and inflammation, thereby linking coagulation with inflammation. Abundant thrombin generation in association with inflammation is considered a major reason for the increased risk for thromboembolic events. We therefore investigated platelet responsiveness to thrombin.
  
  
  METHODS
  In this case-control study 85 patients with Crohn's disease (active CD 42, remission 43) and 30 sex- and age-matched controls were enrolled. Clinical disease activity (Harvey-Bradshaw-Index) was assessed and CD-related data were determined by chart review. Platelets' response to protease activated receptor-1 and -4 (PAR-1, -4) was assessed by whole blood platelet aggregometry (MEA), levels of platelets adhering to monocytes (PMA), and platelet surface P-selectin.
  
  
  RESULTS
  Platelets' aggregation after activation with the specific PAR-1 agonist (SFLLRN) and PAR-4 agonist (AYPGKF) was higher in patients with active CD compared to patients in remission and controls (p=0.0068 and p=0.0023 for SFLLRN, p=0.0019 and 0.0003 for AYPGKF). Likewise, levels of PMA after activation with PAR-1 and PAR-4 receptor agonists were higher in patients with active CD compared to patients in remission and controls (p=0.0001 and p<0.0001 for SFLLRN, p=0.0329 and p=0.0125 for AYPGKF). However, P-selectin expression on human platelets showed heterogeneous results. Only PAR-1 activation of platelets resulted in significant differences between CD patients and controls (p=0.0001 and p=0.0022 for active and inactive CD versus controls, respectively).
  
  
  CONCLUSIONS
  Our data suggest a new mechanism of platelet activation which has the potential to increase risk for thromboembolism in patients with active CD which might be due to platelets poised for thrombin-inducible activation.
authors.affiliation: Department of Anesthesiology, General Intensive Care and Pain Medicine, Division of Cardiothoracic and Vascular Anesthesia and Intensive Care, Medical University of Vienna, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Schmid
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Vogelsang
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Pavol
authors.initials: P
authors.lastname: Papay
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Primas
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Eser
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Gratzer
authors.affiliation: Department of Anesthesiology, General Intensive Care and Pain Medicine, Division of Cardiothoracic and Vascular Anesthesia and Intensive Care, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Handler
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Novacek
authors.affiliation: Department for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Simon
authors.initials: S
authors.lastname: Panzer
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003424:Crohn Disease / Q000097:blood* / Q000150:complications; D005260:Female; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000502:physiology; D015539:Platelet Activation / Q000502:physiology; D010973:Platelet Adhesiveness / Q000502:physiology; D044463:Receptor, PAR-1 / Q000502:physiology*; D018179:Receptors, Thrombin / Q000502:physiology*; D013917:Thrombin / Q000502:physiology*; D013923:Thromboembolism / Q000209:etiology
chemical_list: D019007:P-Selectin; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D013917:Thrombin; C112908:protease-activated receptor 4
keywords: Aggregometry; Crohn's disease; Platelets; Thrombin