A new biomarker quantifies differences in clot microstructure in patients with venous thromboembolism (original) (raw)

Accelerated fibrin clot degradation is associated with arterial thromboembolism in patients following venous thrombosis: a cohort study

Scientific Reports

Several lines of evidence have suggested that patients following venous thromboembolism (VTE) are at higher risk of arterial thromboembolism (ATE). Prothrombotic fibrin clot characteristics were reported in individuals with cardiovascular risk factors. We investigated whether specific fibrin clot properties measured after 3–4 months of anticoagulation characterize VTE patients with subsequent ATE. We enrolled 320 patients following VTE aged below 70 years (median age, 46). Ten patients were lost to follow-up. ATE occurred in 21 individuals after a median 54 (31–68) months during a follow-up of 87.5 months (incidence 0.94%; 95% confidence interval [CI], 0.59–1.4 per patient-year). Patients with ATE had faster fibrin clot degradation, reflected by maximum rate of D-dimer increase during plasma clot lysis induced by tissue-type plasminogen activator (D-Drate) at baseline. Clot permeability, turbidimetric variables, clot lysis time, and thrombin generation were unrelated to ATE. Univari...

Altered fibrin clot structure/function in patients with idiopathic venous thromboembolism and in their relatives

Blood, 2009

We tested the hypothesis that fibrin structure/function is unfavorably altered in patients after idiopathic venous thromboembolism (VTE) and their relatives. Ex vivo plasma fibrin clot permeability, turbidimetry, and efficiency of fibrinolysis were investigated in 100 patients with first-ever VTE, including 34 with pulmonary embolism (PE), 100 first-degree relatives, and 100 asymptomatic controls with no history of thrombotic events. Known thrombophilia, cancer, trauma, and surgery were exclusion criteria. VTE patients and their relatives were characterized by lower clot permeability (P < .001), lower compaction (P < .001), higher maximum clot absorbancy (P < .001), and prolonged clot lysis time (P < .001) than controls, with more pronounced abnormalities, except maximum clot absorbance, in the patients versus relatives (all P < .01). Fibrin clots obtained for PE patients were more permeable, less compact, and were lysed more efficiently compared with deep-vein thrombosis patients (all P < .05) with no differences in their relatives. Being VTE relative, fibrinogen, and C-reactive protein were independent predictors of clot permeability and fibrinolysis time in combined analysis of controls and relatives. We conclude that altered fibrin clot features are associated with idiopathic VTE with a different profile of fibrin variables in PE. Similar features can be detected in VTE relatives. Fibrin properties might represent novel risk factors for thrombosis. (Blood. 2009;114:4272-4278)

Reduced Contraction of Blood Clots in Venous Thromboembolism Is a Potential Thrombogenic and Embologenic Mechanism

TH Open

Contraction (retraction) of the blood clot is a part of the clotting process driven by activated platelets attached to fibrin that can potentially modulate the obstructiveness and integrity of thrombi. The aim of this work was to reveal the pathogenic importance of contraction of clots and thrombi in venous thromboembolism (VTE). We investigated the kinetics of clot contraction in the blood of 55 patients with VTE. In addition, we studied the ultrastructure of ex vivo venous thrombi as well as the morphology and functionality of isolated platelets. Thrombi from VTE patients contained compressed polyhedral erythrocytes, a marker for clot contraction in vivo. The extent and rate of contraction were reduced by twofold in clots from the blood of VTE patients compared with healthy controls. The contraction of clots from the blood of patients with pulmonary embolism was significantly impaired compared with that of those with isolated venous thrombosis, suggesting that less compacted throm...

Biochemical markers for the diagnosis of venous thromboembolism: the past, present and future

Journal of Thrombosis and Thrombolysis, 2010

Deep venous thrombosis and pulmonary embolism represent two expressions of a similar clinical pathological process traditionally referred to as venous thromboembolism. Several population studies evidence venous thromboembolism as a leading healthcare problem worldwide, highlighting the need for early and reliable diagnosis to enable appropriate triage of affected patients and to optimize outcome. There is still debate, however, on which thrombotic markers to use, as well as their most suitable position within diagnostic algorithms. This article aims to review the pathophysiology and clinical usefulness of past, present and future markers of thrombosis, including soluble fibrin monomers, fibrin/fibrinogen degradation products, thrombin-antithrombin complex, plasmin-antiplasmin complex, fibrinopeptide A and B, prothrombin fragments 1 ? 2, thrombus precursor protein, D-dimer, activated protein C-protein C inhibitor complex, myeloperoxidase, thrombin generation assays and proteomic

The worcester venous thromboembolism study

Journal of General Internal Medicine, 2006

BACKGROUND: While there have been marked advances in diagnostic and therapeutic strategies for venous thromboembolism, our understanding of its clinical epidemiology is based on studies conducted more than a decade ago.

Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism

Thrombosis and haemostasis, 2013

In patients with venous thromboembolism (VTE), assessment of the risk of fatal recurrent VTE and fatal bleeding during anticoagulation may help to guide intensity and duration of therapy. We aimed to provide estimates of the case-fatality rate (CFR) of recurrent VTE and major bleeding during anticoagulation in a 'real life' population, and to assess these outcomes according to the initial presentation of VTE and its etiology. The study included 41,826 patients with confirmed VTE from the RIETE registry who received different durations of anticoagulation (mean 7.8 ± 0.6 months). During 27,110 patient-years, the CFR was 12.1% (95% CI, 10.2-14.2) for recurrent VTE, and 19.7% (95% CI, 17.4-22.1) for major bleeding. During the first three months of anticoagulant therapy, the CFR of recurrent VTE was 16.1% (95% CI, 13.6-18.9), compared to 2.0% (95% CI, 0-4.2) beyond this period. The CFR of bleeding was 20.2% (95% CI, 17.5-23.1) during the first three months, compared to 18.2% (95%...

First Episode and Recurrent Venous Thromboembolism: Who is Identifiably at Risk?

Seminars in Vascular Surgery, 2008

Management of venous thromboembolism (VTE) has undergone a significant evolution in the past two decades. Two of the more common heritable thrombophilias were identified (Factor V Leiden and prothrombin 20210A gene mutation) in the early to mid-1990s. These and other inherited and acquired hypercoagulable conditions were found to place patients at higher risk for developing a first episode of VTE. However, their roles in development of recurrent VTE remain uncertain. More recently, other clinical risk factors that are associated with increased risk for VTE have been identified. This information has allowed physicians to stratify the type and duration of anticoagulation based not only on the presence of thrombophilias, but also on other clinical characteristics that increase risk for a first episode of and recurrent VTE.

Venous Thromboembolism: Risk Factors for Recurrence

Arteriosclerosis, Thrombosis, and Vascular Biology, 2009

Patients who have a first episode of venous thromboembolism (VTE) have an elevated risk of a recurrent episode, and this necessitates secondary prophylaxis. Anticoagulant therapy is a double-edged sword, however, as it reduces the risk of recurrent VTE but increases the risk of hemorrhage. This balance must be taken into account when assessing the risk-benefit ratio of long-term anticoagulation. Some clinical characteristics of the index VTE event can help to categorize the individual risk of recurrence. Patients with persistent risk factors such as cancer have a significantly higher risk of recurrent thrombosis. In contrast, VTE provoked by transient risk factors is associated with a lower risk of recurrence. Intrinsic features of patients with VTE (gender, age, hereditary thrombophilia) have also been linked to the risk of recurrent VTE. There is increasing evidence that a normal D-dimer level and the absence of residual venous thrombosis after discontinuation of oral anticoagulation are associated with a lower risk of recurrent VTE events. Future studies are needed to refine the predictive value of known risk factors for VTE recurrence and to discover better markers.