Plasma Tissue Factor Pathway Inhibitor Levels Correlate with Disease Activity and Are Associated with Altered Thrombin Generation in Pediatric Inflammatory Bowel Disease

Background: Patients with inflammatory bowel disease (IBD) exhibit a hypercoagulable state with increased thrombotic risk. Previous studies demonstrated elevated thrombin generation in pediatric IBD, paradoxically accompanied by prolonged lag time during active disease. We hypothesized that elevated tissue factor pathway inhibitor (TFPI) levels during active inflammation contribute to this paradox. Methods: We prospectively enrolled 25 pediatric patients (10 Crohn’s disease [CD], 15 ulcerative colitis [UC]) aged 7–18 years with newly diagnosed IBD. Blood samples were collected at diagnosis and in remission. Thrombin generation was assessed using calibrated automated thrombography. Plasma levels of TFPI, tissue factor activity (TFA), vascular endothelial growth factor (VEGF), and interleukin-6 (IL-6) were measured. Results: TFPI levels correlated positively with thrombin generation lag time (r = 0.43, padj < 0.05) and disease activity scores (r = 0.54, padj < 0.05) in patients with active disease (PCDAI/PUCAI > 0). Longitudinal analysis of 16 patients achieving remission revealed elevated TFPI and prolonged lag time during active disease compared to quiescence (both padj < 0.05), while TFA did not change significantly. VEGF decreased significantly upon remission (padj < 0.05), whereas IL-6 showed no significant change. Conclusions: Elevated TFPI levels during active IBD likely contribute to the paradoxical prolongation of thrombin generation lag time. TFPI normalization upon remission reflects vascular inflammation resolution, suggesting TFPI as a potential biomarker and therapeutic target.