Fibrinolysis in Venous Thromboembolism

Author(s):  
Anetta Undas

AbstractFibrinolysis is of paramount importance in maintaining or regaining the patency of veins and pulmonary arteries obstructed by thrombi. Growing experimental and clinical evidence indicates that impaired fibrinolysis mediated by multiple complex mechanisms is involved in venous thromboembolism (VTE). Global plasma fibrin clot lysis markers, especially clot lysis time, have been reported to predict recurrent deep-vein thrombosis and pulmonary embolism. The current overview summarizes available data linking fibrinolysis to VTE and its long-term sequelae.

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4272-4278 ◽  
Author(s):  
Anetta Undas ◽  
Krystyna Zawilska ◽  
Mariola Ciesla-Dul ◽  
Agata Lehmann-Kopydłowska ◽  
Agnieszka Skubiszak ◽  
...  

Abstract 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.


2015 ◽  
Vol 113 (01) ◽  
pp. 185-192 ◽  
Author(s):  
Chun-Cheng Wang ◽  
Cheng-Li Lin ◽  
Guei-Jane Wang ◽  
Chiz-Tzung Chang ◽  
Fung-Chang Sung ◽  
...  

SummaryWhether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR] = 1.92; 95 % confidence interval [CI] = 1.54-2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97-3.64), respectively. The baseline demographics indicated that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the non-AF group (adjusted HR = 1.74; 95 %CI = 1.36-2.24, adjusted HR = 2.18; 95 %CI = 1.51-3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p<0.01). In conclusion, the presence of AF is associated with increased risk of VTE after a long-term follow-up period.


2017 ◽  
Vol 117 (09) ◽  
pp. 1739-1749 ◽  
Author(s):  
Agnieszka Janion-Sadowska ◽  
Joanna Natorska ◽  
Jakub Siudut ◽  
Michal Zabczyk ◽  
Andrzej Stanisz ◽  
...  

SummaryWe sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (Ks) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2–6 hours (h) after and 20–25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (Ks −12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for Ks and CLT before rivaroxaban intake. At 2–6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (Ks +38 %, and +37 %, CLT −25 % and −25 %, CLT-TAFI −20 % and −24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (Ks −12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20–25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.


2014 ◽  
Vol 27 (5) ◽  
pp. 615 ◽  
Author(s):  
Isabel Fonseca Santos ◽  
Sónia Pereira ◽  
Euan McLeod ◽  
Anne-Laure Guillermin ◽  
Ismini Chatzitheofilou

<p><strong>Introduction:</strong> Venous thromboembolism is a burden on healthcare systems. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (enoxaparin/warfarin) in Portugal for the treatment and secondary prevention of venous thromboembolism.<br /><strong>Material and Methods:</strong> A Markov model was developed using event rates extracted from the EINSTEIN trials supplemented with literature-based estimates of longer-term outcomes. Core outcomes included per patient costs and quality-adjusted life years reported separately per treatment arm and incrementally, as well as cost per quality-adjusted life years gained. The deep vein thrombosis and pulmonary embolism indications were analysed separately. The analyses were conducted from the Portuguese societal perspective and over a 5-year time horizon. Costs and outcomes were discounted at a 5% annual rate. Several scenario analyses were undertaken to explore the impact on results of varying key modeling assumptions.<br /><strong>Results:</strong> Rivaroxaban treatment was associated with cost-savings for the treatment of deep vein thrombosis and was both cost-saving and more effective for the treatment of pulmonary embolism, compared with enoxaparin/warfarin.<br /><strong>Discussion:</strong> The results of the sensitivity and scenario analyses further supported that rivaroxaban is a cost-effective alternative to standard of care treatment. The use of an expert panel to derive some input values and the lack of Portuguese specific utilities were the main limitations.<br /><strong>Conclusion:</strong> Rivaroxaban represents an efficient alternative to using enoxaparin/warfarin in Portugal, as it’s associated with lower costs (for both indications) and greater quality adjusted life years (for the pulmonary embolism indication).</p><p><br /><strong>Keywords: </strong>Venous Thrombosis; Pulmonary Embolism; Rivaroxaban; Venous Thromboembolism.</p>


2017 ◽  
Vol 22 (6) ◽  
pp. 518-524 ◽  
Author(s):  
Marco P Donadini ◽  
Francesco Dentali ◽  
Samuela Pegoraro ◽  
Fulvio Pomero ◽  
Chiara Brignone ◽  
...  

Isolated distal deep vein thrombosis (IDDVT) is a common clinical manifestation of venous thromboembolism (VTE). However, there are only scant and heterogeneous data available on the long-term risk of recurrent VTE after IDDVT, and the optimal therapeutic management remains uncertain. We carried out a retrospective cohort study of consecutive patients diagnosed with symptomatic IDDVT between 2004 and 2011, according to a predefined short-term treatment protocol (low molecular weight heparin (LMWH) for 4–6 weeks). The primary outcome was the occurrence of recurrent VTE. A total of 321 patients were enrolled. IDDVT was associated with a transient risk factor or cancer in 165 (51.4%) and 56 (17.4%) patients, respectively. LMWH was administered for 4–6 weeks to 280 patients (87.2%), who were included in the primary analysis. Overall, during a mean follow-up of 42.3 months, 42 patients (15%) developed recurrent VTE, which occurred as proximal DVT or PE in 21 cases. The recurrence rate of VTE per 100 patient-years was 3.5 in patients with transient risk factors, 7.2 in patients with unprovoked IDDVT, and 5.9 in patients with cancer ( p=0.018). At multivariable analysis, unprovoked IDDVT and previous VTE were significantly associated with recurrent VTE (HR 2.16, 95% CI 1.12–4.16 and HR 1.97, 95% CI 1.01–3.86, respectively). In conclusion, the long-term risk of recurrent VTE after IDDVT treated for 4–6 weeks is not negligible, in particular in patients with unprovoked IDDVT or cancer. Further studies are needed to clarify whether a longer, but definite treatment duration effectively prevents these recurrences.


2019 ◽  
Vol 14 (2) ◽  
pp. 24-28
Author(s):  
D. S. Morozova ◽  
D. A. Evstratov ◽  
P. A. Zharkov

Venous thromboembolism is not a rare complication in children with cancer. Despite the advantages of the treatment of venous thromboembolism there is still a probability of venous thromboembolism recurrence. In adult patients with cancer venous thromboembolism recurrence an influence on the lower survival rate. In children with cancer venous thromboembolism recurrence is a rare complication, but it can significantly reduce the quality of life. Risk factors of venous thromboembolism recurrence in children with cancer are not properly investigated.


2019 ◽  
Vol 24 (2) ◽  
pp. 122-131 ◽  
Author(s):  
Maya Serhal ◽  
Geoffrey D Barnes

Venous thromboembolism (VTE) is a common vascular condition. New medications are available to prevent hospital-associated VTE. Strategies are being studied to increase appropriate diagnostic testing utilization. Management of deep vein thrombosis (DVT) and pulmonary embolism (PE) has evolved with the advent of new anticoagulant options and catheter-directed intervention. In light of this, providers are commonly challenged with the decision regarding inpatient versus outpatient management. Which patients require long-term (> 3 months) anticoagulation is challenging and multiple clinical prediction models may be used to help determine the risk–benefit ratio in each patient. The management of VTE is an ongoing area of research and is rapidly evolving.


2012 ◽  
Vol 27 (1_suppl) ◽  
pp. 155-162 ◽  
Author(s):  
R D Malgor ◽  
A P Gasparis

Objectives: To review the current literature on the outcomes of pharmacomechanical thrombectomy (PMT) for early thrombus removal in patients with venous thromboembolism (VTE). Methods: We searched the MEDLINE database and performed a manual search of the references of selected articles to select reports reporting the outcomes of PMT alone and PMT compared to catheter-direct thrombolysis (CDT). Outcomes of interest included clot lysis rate, incidence of pulmonary embolism, major bleeding, recurrent deep vein thrombosis, number of venograms needed and amount of lytic utilized. Results We found nine articles that reported outcomes of PMT. Three devices were utilized for PMT, the Angiojet, Trellis and Helix. Different thrombolytics were used to facilitate thrombus removal including urokinase, reteplase, tecneteplase, and tissue plasminogen activator (t-PA). Complete and partial thrombus removal were achieved in up to 84% and 64% and 81% and 59% of the limbs treated with PMT and CDT alone, respectively. Data on PE and bleeding risk after PMT compared to CDT are scarce. The duration of the thrombolysis process, amount of lytics and number of venograms were substantially reduced in the patients who had PMT compared to those who underwent CDT alone. Two articles evaluated the obstacles that limit the indication of PMT in patients with VTE. Conclusion: VTE is a prevalent burden in Western societies. The rationale of early thrombus is to reduce valvular damage and improve venous patency in order to reduce the risk of PTS. PMT is a feasible, safe and faster alternative to expedite the thrombolysis process in patients with VTE.


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