J Crohns Colitis. 2024 May 31;18(5):751-761. doi: 10.1093/ecco-jcc/jjad198.

Célia Schellenberg ¹, Jérémy Lagrange ^1 2, Muhammad Usman Ahmed ¹, Djésia Arnone ³, Philippe Campoli ⁴, Huguette Louis ¹, Nina Touly ², Bénédicte Caron ^3 5, François Plénat ⁶, Julien Perrin ^1 7, Peter J Lenting ⁸, Véronique Regnault ¹, Patrick Lacolley ¹, Cécile V Denis ⁸, Laurent Peyrin-Biroulet ^3 5 9

Author information

¹Université de Lorraine, INSERM, DCAC, Nancy, France.

²CHRU Nancy, IHU INFINY, Vandœuvre-lès-Nancy, France.

³Université de Lorraine, INSERM, NGERE, IHU INFINY, Nancy, France.

⁴CHRU Nancy, Anatomie et Cytologie Pathologiques, Nancy, France.

⁵Department of Gastroenterology, CHRU Nancy, Vandœuvre-lès-Nancy, France.

⁶Université de Lorraine, Nancy, France.

⁷CHRU Nancy, Service d'Hématologie Biologique, Nancy, France.

⁸HITh, UMR_S1176, INSERM, Université Paris-Saclay, Le Kremlin-Bicêtre, France.

⁹Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD Center, Neuilly sur Seine, France.

Abstract

Aims: Although the risk of thrombosis is well documented for inflammatory bowel disease [IBD] patients, the underlying pathological mechanism seems to be different from other thrombotic conditions. Determining the factors responsible for the increased risk of thrombosis in IBD would help to improve the management of this frequent complication.

Methods: 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.

Results: 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 also able to detect the presence of active VWF [VWF in its platelet-binding conformation; 3.2 ± 2.7 μg/mL] in the plasma of 30% of all IBD patients. In healthy controls, active VWF levels were <0.3 μg/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 showed a significant worsening of colitis severity in both acute and chronic models.

Conclusion: 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 haemostasis differs from its role in colonic tissue healing, potentially opening new therapeutic avenues for a life-threatening complication in IBD patients.