fibrin and Postthrombotic-Syndrome

 Catheter-directed thrombolysis (CDT) is an effective therapy for acute deep vein thrombosis (DVT). However, predicting the CDT outcomes remains elusive. We hypothesized that the thrombus signal on T1-weighted black-blood magnetic resonance (MR) can provide insight into CDT outcomes in acute DVT patients..  A total of 117 patients with acute iliofemoral DVT were enrolled for T1-weighted black-blood MR before CDT in this prospective study. Based on the signal contrast between thrombus and adjacent muscle, patients were categorized into the iso-intense thrombus (Iso-IT), hyper-intense thrombus (Hyper-IT), and mixed iso-/hyper-intense thrombi (Mixed-IT) groups. Immediate treatment outcome (i.e., vein patency) and long-term treatment outcome (i.e., the incidence rate of postthrombotic syndrome) were accessed by the same expert. Histological analysis and iron quantification were performed on thrombus samples to characterize the content of fibrin, collagen, and the ratio of Fe.  Compared to Mixed-IT and Hyper-IT groups, the Iso-IT group had the best lytic effect (90.5 ± 1.6% vs. 78.4 ± 2.6% vs. 46.5 ± 3.3%,.  Thrombus signal characteristics on T1-weighted black-blood MR is associated with CDT outcomes and possesses potential to serve as a noninvasive approach to guide treatment decision making in acute DVT patients.. · Thrombus signal on T1-weighted black-blood MR is associated with lytic therapeutic outcome in acute DVT patients.. · Presence of iso-intense thrombus revealed by T1-weighted black-blood MRI is associated with successful thrombolysis, low bleeding ratio, and low incidence of the postthrombotic syndrome.. · T1-weighted thrombus signal characteristics may serve as a noninvasive imaging marker to predict CDT treatment outcomes and therefore guide treatment decision making in acute DVT patients..

Topics: Catheters; Femoral Vein; Fibrin; Hemorrhage; Humans; Iliac Vein; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Postphlebitic Syndrome; Postthrombotic Syndrome; Prospective Studies; Retrospective Studies; Thrombolytic Therapy; Treatment Outcome; Venous Thrombosis

Venous ulcers are the most severe manifestation of post-thrombotic syndrome (PTS). We have previously demonstrated that formation of compact fibrin clots resistant to lysis is observed in patients following deep-vein thrombosis (DVT) who developed PTS. The current study investigated whether unfavourable fibrin clot properties can predict post-thrombotic venous ulcers. In a cohort study on 186 consecutive patients following DVT, we determined plasma fibrin clot characteristics, including clot permeability and lysability, inflammatory markers, thrombin generation, fibrinolysis proteins at 3 months since the index event. Occurrence of PTS and venous ulcers was recorded during follow-up (median, 53; range 24 to 76 months). Fifty-seven DVT patients (30.6%) developed PTS, including 12 subjects (6.45%) with a venous ulcer (4 individuals with recurrent ulcers). Patients who developed ulcers compared with the remainder had at enrolment 13.0% lower clot permeability (K

Topics: Adult; alpha-2-Antiplasmin; Body Mass Index; Cohort Studies; Female; Fibrin; Fibrin Clot Lysis Time; Humans; Male; Middle Aged; Postthrombotic Syndrome; Risk Factors; Varicose Ulcer; Venous Thrombosis

The postthrombotic syndrome (PTS) is a severe complication of deep vein thrombosis (DVT). Reduced plasma clot permeability and lysability have been linked to DVT and residual vein obstruction. OBJECTIVES We investigated whether altered fibrin clot properties are associated with the occurrence of PTS.. Plasma fibrin clot permeability (Ks ) and lysability were investigated in a cohort of 197 consecutive patients aged 18 to 65 years recruited 3 months following the first-ever DVT. Patients with severe thrombophilia or comorbidities known to adversely affect clot phenotype were ineligible.. During a 1-year follow-up PTS developed in 48 (24%) patients, who were characterized by lower Ks , prolonged fibrin clot lysis time (CLT) and slower release of D-dimer from clots (D-Drate ), together with higher plasma D-dimer, C-reactive protein and thrombin-activatable fibrinolysis inhibitor (TAFI). No PTS-associated differences in fibrinogen, thrombin generation, factor VIII, other fibrinolysis proteins and the quality of anticoagulation were observed. Ks (r = -0.71), CLT (r = 0.45), D-Drate (r = -0.30) and TAFI activity (r = 0.38) were associated with the Villalta scale (all P < 0.05). Recurrent VTE occurred also more commonly in PTS patients during follow-up and the 26 (13.2%) patients had lower Ks , longer CLT and lower D-Drate (all P < 0.05). A multivariate model adjusted for age, body mass index, fibrinogen and glucose showed that independent predictors of PTS were idiopathic DVT, plasma D-dimer, Ks , D-Drate , tissue plasminogen activator and TAFI activity.. This study demonstrates that formation of more compact fibrin clots displaying impaired susceptibility to lysis predisposes to PTS.

Topics: Adolescent; Adult; Aged; Blood Coagulation; Cohort Studies; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinolysis; Follow-Up Studies; Humans; Male; Middle Aged; Permeability; Postthrombotic Syndrome; Risk; Thrombin; Veins; Venous Thrombosis; Young Adult

Pregnancy-related deep vein thrombosis (DVT) is most common during the late phase of pregnancy and the first 6-weeks postpartum. Pregnancy-related DVT can have long-term complications, specifically post-thrombotic syndrome (PTS). Fibrin network ultrastructure is altered during pregnancy and post-partum. It is therefore essential to evaluate fibrin fiber diameter during and after pregnancy as this may provide insight into pregnancy-related DVT and subsequent PTS.. The fibrin network ultrastructure of females during different phases of pregnancy was compared to that of non-pregnant females to assess possible changes to the fibrin network morphology and fibrin fiber diameter using scanning electron microscopy micrographs.. The fibrin network arrangement was more densely packed during different phases of pregnancy, corresponding to earlier findings. Fibrin diameter decreased significantly during pregnancy, with the greatest decrease occurring during the late phase of pregnancy. The fractal dimensions of fibrin micrographs increased significantly during pregnancy compared to nonpregnant females. These changes are indicative of a simultaneous hypercoagulable and hypofibrinolytic state and correspond to the increased risk of DVT and subsequent development of PTS.. It is critical to identify "vulnerable" females with an inflammatory predisposition to prevent possible DVT and subsequent PTS. Modifiable risk factors like obesity and smoking should be addressed to alleviate the burden on the coagulation system. Morphological and viscoelastic techniques are crucial in assessing the coagulatory health of females during pregnancy.

Topics: Adolescent; Adult; Female; Fibrin; Humans; Microscopy, Electron, Scanning; Postthrombotic Syndrome; Pregnancy; Pregnancy Complications, Hematologic; Venous Thrombosis; Young Adult