Clot structure and fibrinolytic potential in patients with post thrombotic syndrome

• Published in: Thrombosis research Vol. 137; pp. 85 - 91
• Main Authors: Bouman, A.C, McPherson, H, Cheung, Y.W, ten Wolde, M, ten Cate, H, Ariëns, R.A.S, ten Cate-Hoek, A.J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.01.2016
• Subjects: Aged; Blood Coagulation; Clot structure; Deep vein thrombosis; Female; Fibrin Fibrinogen Degradation Products - analysis; Fibrinogen - analysis; Fibrinolysis; Hematology, Oncology and Palliative Medicine; Humans; Male; Middle Aged; Post thrombotic syndrome; Postthrombotic Syndrome - blood; Postthrombotic Syndrome - pathology; Reproducibility of Results; Sensitivity and Specificity; Venous Thrombosis - blood; Venous Thrombosis - pathology; CRP; HI; n/a; C-reactive protein; DVT; tissue plasminogen activator; Clot structure; Factor XIII; TAT; VTE; pro thrombin activatable fibrinolysis inhibitor; interquartile range; 3,3′,5,5′-tetramethylbenzidine; PTS; thrombin-antithrombin complex; oral anticoagulants; FXIII; ethylenediaminetetraacetic acid; proTAFI; post thrombotic syndrome; BMI; Body Mass Index; not applicable; tPA; TMB; IQR; EDTA; Fibrinolysis; deep vein thrombosis; APC; A/C; venous thromboembolism; enzyme-linked immunosorbent assay; healthy individuals; activated protein C; ELISA; Deep vein thrombosis; Post thrombotic syndrome
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2015.11.013

Abstract Introduction Post-thrombotic syndrome (PTS) is a chronic sequel of deep vein thrombosis (DVT). The clot structure and fibrinolytic potential in PTS is currently unknown. Objective To assess the fibrinolytic potential and clot structure in patients with PTS. Materials and methods Patients with a history of DVT were included in a case–control study: patients with PTS (cases n = 30) and without PTS (controls n = 30), and 30 apparently healthy individuals (HI) without venous thromboembolism (VTE) or venous insufficiency were enrolled. Fibrinolysis and clot structure were assessed by turbidimetric assays, permeation, and confocal microscopy. Fibrinogen was measured by Clauss and fibrinogen γ′ by ELISA. Results We observed a significant trend of decreasing maximum turbidity from HI (median 0.52 [IQR 0.46–0.62]), to controls (0.49 [IQR 0.41–0.55]), to cases (0.46 [IQR 0.39–0.49]) p = 0.020. Fibrinogen was lower in patients (cases and controls) (3.69 g/L [IQR 3.31–4.26]) compared to HI (4.17 [IQR 3.69–4.65]) p = 0.041. Patients with recurrent VTE had lower maximum turbidity and lower permeation than patients with one episode of VTE; (0.31 [IQR 0.25–0.39] versus 0.38 [IQR 0.34–0.44] p = 0.008) and (6.0 × 10 − 9 /cm2 [IQR 5.1–7.9] versus 7.7 × 10 − 9 /cm2 [IQR 6.0–10.0] p = 0.047) respectively, at equal fibrinogen levels. There were no differences in lysis time, confocal microscopy, or fibrinogen γ′. Conclusions Lower maximum turbidity, indicating a tendency towards thinner fibres and denser clots, was found in patients with PTS as well as in patients with recurrent VTE. Fibrinogen levels did not explain these differences in clot structure. The abnormal clot structure may contribute to the increased thrombotic risk profile in patients with PTS.