Abstract

Background: Patients with inflammatory bowel diseases (IBD) exhibit chronic inflammation of the digestive tract associated with a prothrombotic shift in the plasmatic coagulation system as well as heightened platelet reactivity and preactivation. Recently, microbial and platelet-derived inorganic polyphosphate has been shown to inhibit tissue factor pathway inhibitor (TFPI), thus, influencing the hemostatic balance during inflammation. We hypothesized that polyphosphate plays a role in the pathophysiology of inflammatory bowel disease resulting in refractoriness to TFPI activity.

Aims: We aimed to determine the hemostatic sensitivity to exogenous TFPI in IBD patients and healthy controls.

Methods: Plasma from pediatric patients with active Crohn's disease (CD) (N=10) or ulcerative colitis (UC) (N=10) and age-matched healthy controls (N=20) was spiked with recombinant TFPI (150 ng/ml). Thrombin generation with/without exogenous TFPI was performed using Calibrated Automated Thrombography. Differences in lag time of thrombin generation with/without TFPI were calculated (∆lag time).

Results: Without addition of exogenous TFPI, IBD patients exhibited a shorter lag time than controls (IBD: 2.65±0.41 min; Controls: 3.72±0.48 min, P<0.001) Addition of exogenous TFPI prolonged the lag time significantly in healthy controls (∆lag time= 4.69±0.61 min; P<0.001), while the lag time was just slightly prolonged in IBD patients (CD: ∆lag time=0.92±0.37 min; P<0.001; UC: ∆lag time=0.34±27 min; P<0.05).

Conclusion: Plasma samples from pediatric IBD patients exhibit refractoriness towards the anticoagulant activity of exogenous TFPI. This hyposensitivity potentially extends to the action of endogenous TFPI which adds to the prothrombotic phenotype associated with IBD. Further studies are needed to determine potential associations with disease activity and the susceptibility to develop thrombosis.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.