Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2017; 23(26): 4796-4805
Published online Jul 14, 2017. doi: 10.3748/wjg.v23.i26.4796
Levels and activities of von Willebrand factor and metalloproteinase with thrombospondin type-1 motif, number 13 in inflammatory bowel diseases
Dorota Cibor, Danuta Owczarek, Saulius Butenas, Kinga Salapa, Tomasz Mach, Anetta Undas
Dorota Cibor, Danuta Owczarek, Tomasz Mach, Department of Gastroenterology, Hepatology and Infectious Diseases, Jagiellonian University Medical College, 31-531 Krakow, Poland
Saulius Butenas, Department of Biochemistry, College of Medicine, University of Vermont, Burlington, VT 05405, United States
Kinga Salapa, Department of Bioinformatics and Telemedicine, Jagiellonian University Medical College, 31-530 Krakow, Poland
Anetta Undas, Institute of Cardiology, Jagiellonian University Medical College, 31-202 Krakow, Poland
Author contributions: Butenas S and Undas A created study concept and designed the research; Cibor D, Owczarek D and Mach T collected the data; Cibor D, Owczarek D, Salapa K, Mach T and Undas A analyzed and interpretated the data; Cibor D, Owczarek D, Salapa K and Undas A drafted the manuscript; Cibor D, Owczarek D, Butenas S, Salapa K, Mach T and Undas A critically revised the manuscript.
Institutional review board statement: The study was reviewed and approved by the Jagiellonian University Bioethics Committee.
Informed consent statement: All study participants provided informed written consent prior to study enrolment.
Data sharing statement: All study participants gave informed consent for data sharing.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Danuta Owczarek, MD, PhD, Department of Gastroenterology, Hepatology and Infectious Diseases, Jagiellonian University Medical College, ul. Sniadeckich 5, 31-531 Krakow, Poland. owczarek@su.krakow.pl
Telephone: +48-12-4247340 Fax: +48-12-4247380
Received: January 29, 2017
Peer-review started: February 10, 2017
First decision: March 3, 2017
Revised: April 7, 2017
Accepted: May 19, 2017
Article in press: May 19, 2017
Published online: July 14, 2017
Processing time: 164 Days and 6.4 Hours
Abstract
AIM

To evaluate the levels of von Willebrand factor (VWF) and metalloproteinase with thrombospondin type-1 motif, number 13 (ADAMTS13) in inflammatory bowel disease (IBD) and correlate them with the disease activity.

METHODS

Consecutive patients with IBD aged 18 years or older were enrolled in the study. Forty-seven patients with ulcerative colitis (UC), 38 with Crohn’s disease (CD), and 50 healthy controls were included. The white blood cell count, haematocrit, platelet count, fibrinogen, partial activated thromboplastin time, C-reactive protein, albumin, VWF antigen level (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), VWF collagen-binding activity (VWF:CB), and ADAMTS13 antigen level (ADAMTS13:Ag) and activity (ADAMTS13act) were measured. The following ratios were assessed: VWF:RCo/VWF:Ag, VWF:CB/VWF:Ag, VWF:Ag/ADAMTS13act, and ADAMTS13act/ADAMTS13:Ag.

RESULTS

Compared to controls, the odds ratio (OR) of an elevated VWF: Ag > 150% was 8.7 (95%CI: 2.7-28.1) in the UC group and 16.2 (95%CI: 4.8-54.0) in the CD group. VWF:CB was lower in UC patients, and active CD was associated with a higher VWF: RCo (+38%). The ORs of VWF:CB/VWF:Ag < 0.7 (a marker of acquired von Willebrand syndrome) in the UC and CD groups were 11.9 (95%CI: 4.4-32.4) and 13.3 (95%CI: 4.6-38.1), respectively. Active UC was associated with lower ADAMTS13:Ag (-23%) and ADAMTS13act (-20%) compared to UC in remission. Patients with active CD had a 15% lower ADAMTS13act than controls. The activity of UC, but not that of CD, was inversely correlated with ADAMTS13:Ag (r = -0.76) and ADAMTS13act (r = -0.81).

CONCLUSION

Complex VWF-ADAMTS13-mediated mechanisms disturb haemostasis in IBD. A reduced WVF:CB is a risk factor for bleeding, while a lower ADAMTS13 level combined with an elevated VWF:Ag could predispose one to thrombosis.

Keywords: ADAMTS13; Inflammatory bowel disease; Thrombosis; Acquired von Willebrand syndrome; von Willebrand factor

Core tip: A tightly regulated balance between von Willebrand factor and metalloproteinase with thrombospondin type-1 motif, number 13 (ADAMTS13) is important for haemostasis, and its dysregulation might predispose one to either thrombotic events or bleeding. We demonstrated a decrease in ADAMTS13act levels in Crohn’s disease (CD) patients, and in ADAMTS13:Ag and ADAMTS13act in ulcerative colitis (UC) patients, in whom these parameters were negatively correlated with disease activity and inflammatory markers. We report for the first time the presence of abnormalities typical of type A2 acquired von Willebrand syndrome in inflammatory bowel disease patients. These findings provide insight into the elevated risk for thromboembolic events and bleeding observed in UC and less frequently in CD.