Plasma fibrinolysis, inflammatory markers, and postthrombotic syndrome: preliminary findings from the Kids-DOTT Biobank.

Abstract

Plasma levels of markers of coagulation and inflammation have been identified as prognostic factors for adult postthrombotic syndrome (PTS). We aimed to determine whether plasma fibrinolytic capacity and cytokine levels during the first 3 months after provoked deep venous thrombosis (DVT) are associated with risk of PTS in young patients. We analyzed plasma biospecimens (6 weeks and 3 months after provoked DVT) and clinical data from a National Heart, Lung, and Blood Institute-sponsored multinational trial of anticoagulation for provoked venous thromboembolism in patients younger than age 21 years (Kids-DOTT). Patients with a provoked extremity DVT who had plasma samples available at both 6-week and 3-month post-DVT time points and PTS assessment at 1 year were included. We measured plasma fibrinolytic capacity using the Clot Formation and Lysis (CloFAL) assay and plasma cytokine levels by multiplex immunoassay. Logistic regression analyses evaluated prognostic associations with PTS. Seventy-nine patients were included (median age, 12.8 years; range, 0.04-20.8 years). PTS developed in 34%. Complete veno-occlusion at 6 weeks after diagnosis of DVT (odds ratio [OR], 3.12; 95% confidence interval [CI], 0.81-11.94; P = .097), low fibrinolytic capacity in plasma at 3 months post-DVT (OR, 2.71; 95% CI, 0.92-7.97; P = .07), and elevated serum amyloid A at 3 months post-DVT (OR, 2.85; 95% CI, 0.98-8.34; P = .055) were identified as putative prognostic factors for development of PTS. In multivariable logistic regression analysis, these factors did not retain a statistically significant independent association with PTS, but these preliminary results warrant further investigation in an independent data set to definitively evaluate these findings and identify additional potential prognostic factors for the development of PTS after a provoked DVT in young patients.