Post-thrombotic syndrome (PTS) is characterized by a fibrotic vein injury after deep vein thrombosis (DVT), resulting in a less compliant vein wall. We sought to quantify the change in vein wall thickness and to determine if vein wall damage, defined as wall thickening, is worsened in patients when DVT fails to resolve by 6 months, and also whether there were differences in blood or plasma levels of proteins associated with tissue remodeling. Patients presenting with suspected lower extremity DVT were evaluated. Ultrasound imaging of the lower extremity venous system was performed, and blood was collected. Patients with DVT received repeat evaluation with blood draw and ultrasound imaging at 6 months. DVT resolution was assessed using ultrasound examination. The thickness of the vein wall was quantified by ultrasound imaging in each segment affected by thrombus, and a contralateral, unaffected vein wall served as a control. Messenger RNA was extracted from whole blood using the PAXgene system, and serum proteins were analyzed using enzyme-linked immunosorbent assay (ELISA). Analysis of variance or t tests were used. P < .05 was significant. Thirty patients (10 with DVT resolution at 6 months, 10 with persistent thrombus, and 10 healthy controls) were compared. Resolving and nonresolving DVT were both associated with 1.5- to 1.8-fold increased vein wall thickness at 6 months (n = 10-12; P = .008) compared with nonaffected vein wall segments. However, the thickness of the affected segments was 1.4-fold greater in patients who had total resolution of the DVT by 6 months than in patients who had persistent chronic thrombus 6 months after presentation (n = 10-12; P = .01,). There was a four- to fivefold increased level of MMP-9 in all thrombosed groups compared with controls (n = 5; P < .05). Toll-like receptor-9 (TLR-9) expression was threefold less than in controls (n = 5; P < .05). There were no statistically significant differences in the levels of associated factors such as D-dimer, P-selectin, or inflammatory and remodeling markers such as SLC or matrix metalloproteinase (MMP)-2 by ELISA. There were no significant differences in the gene expression of C-reactive protein, MMP-2, MMP-9, or TLR-4. This preliminary study suggests ongoing vein wall remodeling after DVT. At 6 months, the vein wall is markedly thickened, but this change is independent of thrombus resolution and is associated with elevated MMP-9 but not other inflammatory markers. This suggests that the vein wall damage is initiated early after thrombus formation and persists even in the presence of total resolution.

Background: Post-thrombotic syndrome (PTS) is characterized by a fibrotic vein injury following deep vein thrombosis (DVT), resulting in a less compliant vein wall. We sought to quantify the change in vein wall thickness, and to determine if vein wall damage, defined as wall thickening, is worsened in patients who fail to resolve DVT by six months, and whether there were differences in blood or plasma levels of proteins associated with tissue remodelling. Methods: Patients presenting with suspected lower extremity DVT were evaluated. Ultrasound imaging of the lower extremity venous system was performed and blood was collected. Patients with DVT received repeat evaluation with blood draw and ultrasound imaging at six months. DVT resolution was assessed using ultrasound examination. The thickness of the vein wall was quantified by ultrasound imaging in each segment affected by thrombus, and a contralateral, unaffected vein wall served as a control. mRNA was extracted from whole blood using the PAXgene system, and serum proteins were analysed using enzyme-linked immunosorbent assay (ELISA). Analysis of variance or Student’s t-tests were used and a P , 0.05 was significant. Results: Thirty patients (10 patients with DVTresolution at six months, 10 patients with persistent thrombus and 10 healthy controls) were compared. Both resolving and non-resolving DVT were associated with 1.5–1.8-fold increased vein wall thickness at six months (n 1⁄4 10–12; P 1⁄4 0.008) as compared with non-affected vein wall segments. However, the thickness of the affected segments was 1.4-fold greater in patients who had a total resolution of the DVT by six months than in patients who had persistent chronic thrombus six months after presentation (N 1⁄4 10–12; P 1⁄4 0.01). There was a 4–5-fold increased level of matrix metalloproteinase (MMP)-9 in all thrombosed groups compared with controls (n 1⁄4 ; P , 0.05), while Toll-like receptor-9 (TLR-9) expression was threefold less than controls (n 1⁄4 ; P , 0.05). There were no statistically significant differences in the levels of associated factors such as D-dimer, P-selectin or inflammatory and remodelling markers such as SLC or MMP-2 by ELISA. There were no significant differences in the gene expression of C-reactive protein, MMP-2, MMP-9 or TLR-4. Conclusion: This preliminary study suggests ongoing vein wall remodelling after DVT. At six months, the vein wall is markedly thickened, but this change is independent of thrombus resolution, and associated with elevated MMP-9 but not other inflammatory markers. This suggests that the vein wall damage is initiated early following thrombus formation and persists even in the presence of total resolution.