Biomarkers for post-thrombotic syndrome

Abstract

Background: Post-thrombotic syndrome (PTS) is a serious condition that occurs in 20%-50% of patients following deep venous thrombosis (DVT). Biomarkers can be of use in further exploring the etiology as well as in developing risk stratification tools for PTS. The relationship between PTS and specific biomarkers may help guide prevention and therapy based on a patient's individual risk profile. This review gives an overview of the current knowledge on biomarkers in relation to PTS.

Methods: A systematic search was executed in three databases (Pubmed, Embase/Medline, Cochrane) to identify all publications on biomarkers in relation to PTS. Where possible, results of studies were pooled and a meta-analysis was performed using Review Manager 5.1 (The Cochrane Collaboration).

Results: Twenty-four papers were included in this review. In patients after DVT, increased D-dimer appeared to be associated with the development of PTS (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.02-4.08; P = .04). Neither prothrombin G20210A (OR, 0.95; 95% CI, 0.53-1.69; P = .86, nor increased factor VIII (OR, 1.78; 95% CI, 0.88-3.57; P = .11) were associated with PTS. For factor V Leiden (FVL), conflicting results were found. FVL was not associated with PTS within a population of patients with a history of DVT (OR, 0.98; 95% CI, 0.74-1.29; P = .88), but FVL was positively associated with post-thrombotic ulceration in severe PTS, in patients compared with healthy individuals without a history of DVT (OR, 11.42; 95% CI, 6.37-20.48; P < .00001). A meta-analysis could not be performed for markers of inflammation and tissue remodelling in relation to PTS.

Conclusions: Increased D-dimer levels are associated with a twofold increased risk for PTS. Inherited hypercoagulability, including FVL is not associated with PTS in general. In contrast, FVL is strongly associated with post-thrombotic ulceration in severe PTS. The role of inflammation in the etiology of PTS still has to be elucidated.