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

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4272-4278 ◽  
Author(s):  
Anetta Undas ◽  
Krystyna Zawilska ◽  
Mariola Ciesla-Dul ◽  
Agata Lehmann-Kopydłowska ◽  
Agnieszka Skubiszak ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Structure Function ◽  
Ex Vivo ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Vein Thrombosis ◽  
Reactive Protein ◽  
History Of ◽  
Deep Vein ◽  
Clot Structure

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.

Fibrinolysis in Venous Thromboembolism

2021 ◽  
Author(s):  
Anetta Undas
Keyword(s):  
Venous Thromboembolism ◽  
Clinical Evidence ◽  
Pulmonary Arteries ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Vein Thrombosis ◽  
Lysis Time ◽  
Recurrent Deep Vein Thrombosis ◽  
Deep Vein

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.

Altered fibrin clot structure/function in patients with antiphospholipid syndrome: association with thrombotic manifestation

2014 ◽  
Vol 112 (08) ◽  
pp. 287-296 ◽  
Author(s):  
Magdalena Celińska-Löwenhoff ◽  
Teresa Iwaniec ◽  
Agnieszka Padjas ◽  
Jacek Musiał ◽  
Anetta Undas
Keyword(s):  
Structure Function ◽  
Antiphospholipid Syndrome ◽  
Thrombotic Event ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Lag Phase ◽  
Lysis Time ◽  
Clot Structure ◽  
Clot Lysis Time ◽  
D Dimer

SummaryWe tested the hypothesis that plasma fibrin clot structure/function is unfavourably altered in patients with antiphospholipid syndrome (APS). Ex vivo plasma clot permeability, turbidity and susceptibility to lysis were determined in 126 consecutive patients with APS enrolled five months or more since thrombotic event vs 105 controls. Patients with both primary and secondary APS were characterised by 11% lower clot permeability (p<0.001), 4.8% shorter lag phase (p<0.001), 10% longer clot lysis time (p<0.001), and 4.7% higher maximum level of D-dimer released from clots (p=0.02) as compared to the controls. Scanning electron microscopy images confirmed denser fibrin networks composed of thinner fibres in APS. Clots from patients with “triple-antibody positivity” were formed after shorter lag phase (p=0.019) and were lysed at a slower rate (p=0.004) than in the remainder. Clots from APS patients who experienced stroke and/or myocardial infarction were 8% less permeable (p=0.01) and susceptible to lysis (10.4% longer clot lysis time [p=0.006] and 4.5% slower release of D-dimer from clots [p=0.01]) compared with those following venous thromboembolism alone. Multivariate analysis adjusted for potential confounders showed that in APS patients, lupus anticoagulant and “triple-positivity” were the independent predictors of clot permeability, while “triple-positivity” predicted lysis time. We conclude that APS is associated with prothrombotic plasma fibrin clot phenotype, with more pronounced abnormalities in arterial thrombosis. Molecular background for this novel prothrombotic mechanism in APS remains to be established.

Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban

2017 ◽  
Vol 117 (09) ◽  
pp. 1739-1749 ◽  
Author(s):  
Agnieszka Janion-Sadowska ◽  
Joanna Natorska ◽  
Jakub Siudut ◽  
Michal Zabczyk ◽  
Andrzej Stanisz ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Mutation Carriers ◽  
Lysis Time ◽  
Prothrombin Mutation ◽  
Fibrinolysis Inhibitor ◽  
Heterozygous Carriers ◽  
Mutation Group ◽  
Clot Structure

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.

Multimodal prophylaxis in patients with a history of venous thromboembolism undergoing primary elective hip arthroplasty

2020 ◽  
Vol 102-B (7_Supple_B) ◽  
pp. 71-77
Author(s):  
Alejandro Gonzalez Della Valle ◽  
Kate A. Shanaghan ◽  
Joseph Nguyen ◽  
Jiabin Liu ◽  
Stavros Memtsoudis ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Hip Arthroplasty ◽  
Vena Cava ◽  
Haemorrhagic Stroke ◽  
International Normalized Ratio ◽  
First Year ◽  
Vein Thrombosis ◽  
History Of ◽  
One Year ◽  
Deep Vein

Aims We studied the safety and efficacy of multimodal thromboprophylaxis in patients with a history of venous thromboembolism (VTE) who undergo total hip arthroplasty (THA) within the first 120 postoperative days, and the mortality during the first year. Multimodal prophylaxis includes discontinuation of procoagulant medications, VTE risk stratification, regional anaesthesia, an intravenous bolus of unfractionated heparin prior to femoral preparation, rapid mobilization, the use of pneumatic compression devices, and chemoprophylaxis tailored to the patient’s risk of VTE. Methods Between 2004 to 2018, 257 patients with a proven history of VTE underwent 277 primary elective THA procedures by two surgeons at a single institution. The patients had a history of deep vein thrombosis (DVT) (186, 67%), pulmonary embolism (PE) (43, 15.5%), or both (48, 17.5%). Chemoprophylaxis included aspirin (38 patients), anticoagulation (215 patients), or a combination of aspirin and anticoagulation (24 patients). A total of 50 patients (18%) had a vena cava filter in situ at the time of surgery. Patients were followed for 120 days to record complications, and for one year to record mortality. Results Postoperative VTE was diagnosed in seven patients (2.5%): DVT in five, and PE with and without DVT in one patient each. After hospitalization, three patients required readmiss-ion for evacuation of a haematoma, one for wound drainage, and one for monitoring of an elevated international normalized ratio (INR). Seven patients died (2.5%). One patient died five months postoperatively of a PE during open thrombectomy. She had discontinued anticoagulation. One patient died of a haemorrhagic stroke while receiving Coumadin. PE or bleeding was not suspected in the remaining five fatalities. Conclusion Multimodal prophylaxis is safe and effective in patients with a history of VTE. Postoperative anticoagulation should be prudent as very few patients developed VTE (2.5%) or died of suspected or confirmed PE. Mortality during the first year was mostly unrelated to either VTE or bleeding. Cite this article: Bone Joint J 2020;102-B(7 Supple B):71–77.

scholarly journals Pregnancy-Associated Venous Thromboembolism: Insights from GARFIELD-VTE

TH Open ◽  
2021 ◽  
Vol 05 (01) ◽  
pp. e24-e34
Author(s):  
Carlos Jerjes-Sánchez ◽  
David Rodriguez ◽  
Alfredo E. Farjat ◽  
Gloria Kayani ◽  
Peter MacCallum ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Childbearing Age ◽  
Diagnostic Strategies ◽  
Vein Thrombosis ◽  
All Cause Mortality ◽  
History Of ◽  
Common Risk Factors ◽  
Deep Vein ◽  
Compression Ultrasonography

Abstract Introduction The risk of venous thromboembolism (VTE) increases during pregnancy and the puerperium such that VTE is a leading cause of maternal mortality. Methods We describe the clinical characteristics, diagnostic strategies, treatment patterns, and outcomes of women with pregnancy-associated VTE (PA-VTE) enrolled in the Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE. Women of childbearing age (<45 years) were stratified into those with PA-VTE (n = 183), which included pregnant patients and those within the puerperium, and those with nonpregnancy associated VTE (NPA-VTE; n = 1,187). Patients with PA-VTE were not stratified based upon the stage of pregnancy or puerperium. Results Women with PA-VTE were younger (30.5 vs. 34.8 years), less likely to have pulmonary embolism (PE) (19.7 vs. 32.3%) and more likely to have left-sided deep vein thrombosis (DVT) (73.9 vs. 54.8%) compared with those with NPA-VTE. The most common risk factors in PA-VTE patients were hospitalization (10.4%), previous surgery (10.4%), and family history of VTE (9.3%). DVT was typically diagnosed by compression ultrasonography (98.7%) and PE by chest computed tomography (75.0%). PA-VTE patients more often received parenteral (43.2 vs. 15.1%) or vitamin K antagonists (VKA) (9.3 vs. 7.6%) therapy alone. NPA-VTE patients more often received a DOAC alone (30.2 vs. 13.7%). The risk (hazard ratio [95% confidence interval]) of all-cause mortality (0.59 [0.18–1.98]), recurrent VTE (0.82 [0.34–1.94]), and major bleeding (1.13 [0.33–3.90]) were comparable between PA-VTE and NPA-VTE patients. Uterine bleeding was the most common complication in both groups. Conclusion VKAs or DOACs are widely used for treatment of PA-VTE despite limited evidence for their use in this population. Rates of clinical outcomes were comparable between groups.

scholarly journals Symptomatic perioperative venous thromboembolism is a frequent complication in patients with a history of deep vein thrombosis

2010 ◽  
Vol 52 (3) ◽  
pp. 651-657 ◽  
Author(s):  
Timothy K. Liem ◽  
Thanh M. Huynh ◽  
Shannon E. Moseley ◽  
Renee C. Minjarez ◽  
Gregory J. Landry ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Frequent Complication ◽  
Vein Thrombosis ◽  
History Of ◽  
Deep Vein

scholarly journals Venous Thromboembolism in Patients Discharged after COVID-19 Hospitalization

2021 ◽  
Author(s):  
Matthias M. Engelen ◽  
Christophe Vandenbriele ◽  
Tim Balthazar ◽  
Eveline Claeys ◽  
Jan Gunst ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
C Reactive Protein ◽  
Systematic Screening ◽  
Vein Thrombosis ◽  
Reactive Protein ◽  
Risk Patients ◽  
Deep Vein ◽  
D Dimer

Abstract Background Venous thromboembolism (VTE) is a frequent complication of COVID-19, so that the importance of adequate in-hospital thromboprophylaxis in patients hospitalized with COVID-19 is well established. However, the incidence of VTE after discharge and whether postdischarge thromboprophylaxis is beneficial and safe are unclear. In this prospective observational single-center study, we report the incidence of VTE 6 weeks after hospitalization and the use of postdischarge thromboprophylaxis. Methods Patients hospitalized with confirmed COVID-19 were invited to a multidisciplinary follow-up clinic 6 weeks after discharge. D-dimer and C-reactive protein were measured, and all patients were screened for deep vein thrombosis with venous duplex-ultrasound. Additionally, selected high-risk patients received computed tomography pulmonary angiogram or ventilation–perfusion (V/Q) scan to screen for incidental pulmonary embolism. Results Of 485 consecutive patients hospitalized from March through June 2020, 146 patients were analyzed, of which 39% had been admitted to the intensive care unit (ICU). Postdischarge thromboprophylaxis was prescribed in 28% of patients, but was used more frequently after ICU stay (61%) and in patients with higher maximal D-dimer and C-reactive protein levels during hospitalization. Six weeks after discharge, elevated D-dimer values were present in 32% of ward and 42% of ICU patients. Only one asymptomatic deep vein thrombosis (0.7%) and one symptomatic pulmonary embolism (0.7%) were diagnosed with systematic screening. No bleedings were reported. Conclusion In patients who had been hospitalized with COVID-19, systematic screening for VTE 6 weeks after discharge revealed a low incidence of VTE. A strategy of selectively providing postdischarge thromboprophylaxis in high-risk patients seems safe and potentially effective.

scholarly journals Design and Baseline Data for a Prospective Observational Study of Rivaroxaban in Patients with Venous Thromboembolism in Japan (XASSENT)

TH Open ◽  
2021 ◽  
Author(s):  
Ikuo Fukuda ◽  
Atsushi Hirayama ◽  
Kazuo Kawasugi ◽  
Takao Kobayashi ◽  
Hideaki Maeda ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Patient Characteristics ◽  
Open Label ◽  
Phase 3 ◽  
Vein Thrombosis ◽  
Post Marketing Surveillance ◽  
Post Marketing ◽  
History Of ◽  
Deep Vein

Background The efficacy and safety of rivaroxaban have been demonstrated in phase 3 trials of patients with venous thromboembolism (VTE; pulmonary embolism [PE] and deep vein thrombosis [DVT]). Data regarding rivaroxaban treatment of VTE in routine Japanese clinical practice remain limited. Objectives XASSENT will evaluate rivaroxaban treatment of VTE in real-world Japanese clinical practice. We report the study design and baseline patient characteristics. Methods XASSENT (NCT02558465) is a an open-label, prospective observational, post-marketing surveillance cohort study in patients receiving rivaroxaban treatment for VTE. Enrolment took place between November 2015 and March 2018. XASSENT will follow patients for up to 2 years. Primary outcome variables: major bleeding and symptomatic recurrent VTE. Statistical analyses are exploratory and descriptive. Results Baseline patient characteristics at June 2020 (n=2,299) are presented (58.2% female; mean age 66.7 years; mean weight 60.9kg). The population encompasses patients with wide-ranging characteristics including older age, low weight, and renal dysfunction. Most participants (67.6%) had a history of VTE risk factors at baseline. Half of the population (50.4%) had DVT only; 41.4% had DVT with PE; 8.2% had PE only. Overall, 68.4% were inpatients and 77.1% had symptomatic VTE. Rivaroxaban was prescribed for initial treatment in 84.6% of patients and maintenance treatment in 15.4%. Most were prescribed the approved dose of rivaroxaban for initial (30mg daily; 84.4%) or maintenance (15mg daily; 81.9%) treatment of VTE in Japan. The most common reason for selecting non-recommended dose was ‘elderly’. Conclusions Results from XASSENT will complement phase 3 trial data and inform clinical practice.

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