Low-Grade Activation of the Extrinsic Coagulation Pathway in Patients with Ulcerative Colitis

Background

Ulcerative colitis (UC) increases the risk for venous thromboembolism. Tissue factor (TF) initiates the extrinsic coagulation pathway (ECP).

Aims

To investigate the correlation of UC severity with latent ECP activation and TF expression in primary colonic stromal cells (PCSC).

Methods

In plasma of 38 UC patients (31 males, disease duration 151 ± 25 months) and 28 healthy controls, exosomes and microparticles (EM) were counted. Moreover, TF protein concentration, activities of EM-bound TF (EM-TFa) and coagulation factor VII (FVIIa) were assessed. In PCSC in culture, TF mRNA (F3) from 12 patients with active UC and 7 controls was evaluated.

Results

UC patients had 4– and 3.7– times more exosomes and microparticles, respectively, than controls. TF protein in UC was correlated with several disease severity indices, such as partial Mayo score (pMs; r 0.443), albumin (− 0.362), ESR (0.353), PLT (0.575), and endoscopic Ms (eMs 0.468). EM-TFa was also significantly higher in UC and was correlated to SIBDQ (− 0.64), albumin (− 0.624), disease extent and eMs (0.422). Refractory-to-treatment patients had significantly higher TF protein, EM-TFa and FVIIa. Even within responders, the need for steroids or biologics correlated with a 2.2–times higher EM-TFa. PCSC from active UC maintained higher F3 than controls, which was correlated to pMs (0.56), albumin (− 0.543) and eMs. Treatment with cytokines further upregulated F3. P for all comparisons was < 0.05.

Conclusion

Low-grade activation of the ECP associates with clinical, endoscopic UC activity and response to treatment. TF in PCSC mirrors its systemic activity and points to them as a source.

Graphical Abstract