Markers of coagulation, fibrinolysis and inflammation in relation to post-thrombotic syndrome

Background: Post-thrombotic syndrome (PTS) occurs in 2050% of patients after a deep venous thrombosis (DVT). It is difficult to accurately predict which patients will develop PTS. Biomarkers could be a valuable tool for PTS risk assessment. Objectives: To investigate whether increased levels of factor (F)VIII, C-reactive protein (CRP) or D-dimer, over time, are associated with the development of PTS in patients after an acute DVT. Methods: PTS status was assessed using the Villalta scale. Blood sampling was performed at three points during follow-up. Results: A cohort of 228 consecutive patients was included after an acute DVT. At T1 (12 months after index DVT), both levels of D-dimer (median 725 ng mL-1 [interquartile range, IQR 4001400[ vs. 378 ng mL-1 [251652] P = 0.004) and CRP (median 3.9 mg L-1 [IQR 1.68.5] vs. 2.4 mg L-1 [1.04.3] P = 0.018) were increased in patients with PTS, compared with patients without PTS. Factor (F)VIII was not associated with PTS. In the multivariate logistic regression analysis, varicosities (odds ratio [OR] 13.4 95% confidence interval [CI] 3.059.1 P = 0.001), a previous ipsilateral DVT (OR 6.3 95% CI 1.526.9 P = 0.012) and CRP > 5 mg L-1 on T1 (OR 8.0 95% CI 2.426.4 P = 0.001) were significantly associated with PTS. Conclusions: Besides previous ipsilateral DVT and varicosities, CRP > 5 mg L-1 at T1 was strongly and independently associated with PTS. Persistent inflammation rather than hypercoagulability might be the most important etiological factor in PTS, and may be a target for future therapy. The development of a risk score for PTS, including both clinical risk factors and biomarker levels, such as CRP, might be desirable.