炎症性肠病
血小板
血管性血友病因子
止血
医学
凝结
结肠炎
免疫学
血栓形成
血管性血友病
溃疡性结肠炎
凝血病
血小板活化
炎症
内科学
胃肠病学
疾病
作者
Célia Schellenberg,Jérémy Lagrange,Muhammad Usman Ahmed,Djésia Arnone,Philippe Campoli,Huguette Louis,Nina Touly,Bénédicte Caron,François Plénat,Julien Perrin,Peter J. Lenting,V. Régnault,Patrick Lacolley,Cécile V. Denis,Laurent Peyrin–Biroulet
出处
期刊:Journal of Crohn's and Colitis
[Oxford University Press]
日期:2023-11-27
标识
DOI:10.1093/ecco-jcc/jjad198
摘要
Although the risk for thrombosis is well documented for inflammatory bowel disease (IBD) patients, the underlying pathological mechanism seems to be different from other thrombotic conditions. Deciphering the actors responsible for the increased risk of thrombosis in IBD would help to improve management of this frequent complication.We studied the interplay between platelets, coagulation, and von Willebrand factor (VWF) in 193 IBD patients and in experimental models (acute and chronic) of colitis in wild-type and VWF-deficient mice.We found a platelet-dependent increase in thrombin generation in IBD patients and in our mouse model of colitis. Agglutinated platelets were present in the blood of patients and mice. Interestingly, we observed not only a significant increase in total VWF antigen, but we were able to detect the presence of active VWF (VWF in its platelet-binding conformation; 3.2±2.7µg/ml) in the plasma of 30% of all IBD patients. In healthy controls, active VWF levels were below 0.3µg/ml. This led us to further explore experimental colitis in VWF-deficient mice and we observed that these mice were protected against the procoagulant state triggered by the colitis. Unexpectedly, these mice also manifested a significant worsening of colitis severity both in acute and chronic models.Platelets and VWF (including its active form) appear to be central players in the procoagulant phenotype in IBD. We observed that the role of VWF in hemostasis differs from its role in colic tissue healing, potentially opening new therapeutic avenues for a life-threatening complication in IBD patients.
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