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J Crohns Colitis. 2014 Jun;8(6):495-503. doi: 10.1016/j.crohns.2013.11.001. Epub 2013 Dec 2.

Increased responsiveness to thrombin through protease-activated receptors (PAR)-1 and -4 in active Crohn's disease.

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Department of Anesthesiology, General Intensive Care and Pain Medicine, Division of Cardiothoracic and Vascular Anesthesia and Intensive Care, Medical University of Vienna, Vienna, Austria.
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Department for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.



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.


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.


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).


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.


Aggregometry; Crohn's disease; Platelets; Thrombin

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