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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.

Author information

1
Department of Anesthesiology, General Intensive Care and Pain Medicine, Division of Cardiothoracic and Vascular Anesthesia and Intensive Care, Medical University of Vienna, Vienna, Austria.
2
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
3
Department for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.

Abstract

BACKGROUND AND AIMS:

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.

KEYWORDS:

Aggregometry; Crohn's disease; Platelets; Thrombin

PMID:
24291018
DOI:
10.1016/j.crohns.2013.11.001
[Indexed for MEDLINE]

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