The Occurrence of Thrombosis in Inflammatory Bowel Disease Is Reflected in the Clot Lysis Profile

Lize Bollen, Niels Vande Casteele, Miet Peeters, Gert Van Assche, Marc Ferrante, Wouter Van Moerkercke, Paul Declerck, Séverine Vermeire, Ann Gils, Lize Bollen, Niels Vande Casteele, Miet Peeters, Gert Van Assche, Marc Ferrante, Wouter Van Moerkercke, Paul Declerck, Séverine Vermeire, Ann Gils

Abstract

Background: The occurrence of thromboembolic events (TE) is an important extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The aim of this study was to compare fibrinolysis and clot lysis parameters between (1) patients with IBD and healthy controls and (2) patients with IBD with TE (IBD + TE) and without TE (IBD - TE).

Methods: One hundred thirteen healthy controls and 202 patients with IBD, of which 84 patients with IBD + TE and 118 patients with IBD - TE, were included in this case-control study. Three clot lysis parameters (area under the curve, 50% clot lysis time, and amplitude) were determined using a clot lysis assay. Plasminogen activator inhibitor 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor concentrations were determined by enzyme-linked immunosorbent assay.

Results: PAI-1 antigen, active PAI-1, and intact thrombin activatable fibrinolysis inhibitor concentrations, as well as 50% clot lysis time and area under the curve, were significantly associated with the presence of IBD (all P < 0.05). The median time between TE and plasma collection was 5.0 (1.8-11.0) years. Comparing IBD + TE versus IBD - TE, active to total PAI-1 ratio (0.36 [0.24-0.61] versus 0.24 [0.13-0.40]), area under the curve (31 [24-49] versus 22 [13-31]), 50% clot lysis time (110 [64-132] versus 95 [70-126] minutes), and amplitude (0.295 [0.222-0.436] versus 0.241 [0.168-0.308]) were significantly higher in IBD + TE (all P <0.05) and remained higher after adjustment for age, gender, C-reactive protein, type of disease, presence of comorbidities, and disease activity.

Conclusions: Patients with IBD have an altered clot lysis profile compared with healthy controls. Clot lysis parameters differ significantly between patients with IBD with and without a history of TE and should be included in the risk assessment.

Conflict of interest statement

L. Bollen is a Research Assistant of the Research Foundation-Flanders (FWO-Vlaanderen), Belgium. N. Vande Casteele received lectures and consultancy fees from AbbVie, MSD and Janssen Biologics, UCB, and Pfizer. G. Van Assche received financial support for research from MSD and AbbVie; received lecture fees from MSD, AbbVie, Takeda, and Ferring; consultant for MSD, AbbVie, Takeda, Ferring, Genentech/Roch, and Pfizer. M. Ferrante received financial support for research from Takeda; received lecture fees from MSD, AbbVie, Janssen, Chiesi, Tillotts, and Zeira; consultant for AbbVie, Janssen, MSD, Boehringer Ingelheim, and Ferring. S. Vermeire received financial support for research from MSD and AbbVie; received lectures fees from MSD, AbbVie, Takeda, Falk, and Tillotts; is a consultant for MSD, AbbVie, Takeda, Falk, Ferring, Shire, Galapagos, Hospira, Mundipharma, Genentech/Roch, Pfizer, and Celgene. A. Gils received financial support for research from Pfizer; received lectures fees from MSD, AbbVie, Janssen Biologics, and Pfizer. The remaining authors have no conflict of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Receiver operating curve of the clot lysis parameter AUC, patients with IBD + TE compared with HC. The clot lysis parameter AUC had an area under the receiver operating curve (95% CI) of 0.80 (0.73–0.87). The cross depicted in black presents the best top-left cutoff, 23 optical density × minutes, with a specificity of 73% and a sensitivity of 77%.
FIGURE 2
FIGURE 2
Proposal for a risk assessment for patients with IBD at risk to develop a thrombosis. Patients with IBD are stratified according to their general and IBD-specific risk factors for TE into high-risk patients and intermediate/low-risk patients. Hospitalized patients with IBD or patients with IBD with multiple general risk factors are considered “high risk” and thromboprophylaxis is recommended. For nonhospitalized patients with IBD, the need for thromboprophylaxis is less clear. Patients with IBD with risk factors such as surgery in the previous 6 months, a history of TE, IBD flares, prolonged immobility, or long-time steroid treatment are considered more at risk for TE. A global clot lysis assay will help, in this particular case, to determine if the patient is considered as “intermediate risk,” then thromboprophylaxis is recommended, or “low risk,” then no thromboprophylaxis is recommended.

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