Venous Thromboembolism in Patients with Liver Cirrhosis: Findings from the RIETE (Registro Informatizado de la Enfermedad TromboEmbolica) Registry

AbstractPatients with cirrhosis are not only at an increased risk of bleeding but also at risk of venous thromboembolism (VTE). We sought to determine the clinical characteristics, management, and outcomes after VTE in patients with cirrhosis. We used the data from RIETE (Registro Informatizado de la Enfermedad TromboEmbolica), an international registry of patients with VTE, to compare the outcomes in patients with and without cirrhosis. Main outcomes included all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent VTE, and bleeding. Among 43,611 patients with acute VTE, 187 (0.4%) had cirrhosis. Of these, 184 (98.4%) received anticoagulation for a median of 109 days (interquartile range [IQR]: 43–201 days), most commonly with enoxaparin (median dose: 1.77 [IQR: 1.38–2.00] mg/kg/day). Compared with patients without cirrhosis, those with cirrhosis had a higher rate of all-cause mortality (10.7 vs. 3.4%; odds ratio [OR]: 3.41; 95% confidence interval [CI]: 2.03–5.46) and fatal bleeding (2.1 vs. 0.2%; OR: 13.94; 95% CI: 3.65–37.90) but similar rates of fatal PE (0.5 vs. 0.5%; OR: 1.17; 95% CI: 0.03–6.70). Patients with cirrhosis had a higher rate of all-cause mortality per 100 patient-years of follow-up (58.9 vs. 16.0; hazard ratio [HR]: 3.70; 95% CI: 2.69–4.91). One-year hazard ratio of clinically relevant bleeding (HR: 2.86; 95% CI: 1.91–4.27), fatal bleeding (HR: 8.51; 95% CI: 3.5–20.7), or recurrent VTE (HR: 2.08; 95% CI: 1.00–4.36) was higher in patients with cirrhosis. Cirrhosis is a challenging comorbidity in patients with VTE. Most patients were treated with anticoagulation and had an elevated risk of recurrence, similar risk of fatal PE, and a very high risk of bleeding including fatal bleeds.

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Non-OO blood type influences the risk of recurrent venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th13-06-0488 ◽

2013 ◽

Vol 110 (12) ◽

pp. 1172-1179 ◽

Cited By ~ 33

Author(s):

Esteban Gándara ◽

Michael J. Kovacs ◽

Susan R. Kahn ◽

Philip S. Wells ◽

David A. Anderson ◽

...

Keyword(s):

Risk Factor ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Oral Anticoagulation ◽

Blood Type ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

Abo Blood Type ◽

Recurrent Vte

SummaryThe role of ABO blood type as a risk factor for recurrent venous thromboembolism (VTE) in patients with a first unprovoked VTE who complete oral anticoagulation therapy is unknown. The aim of this study was to determine if non-OO blood type is a risk factor for recurrent VTE in patients with a first unprovoked VTE who completed 5–7 months of anticoagulant therapy. In an ongoing cohort study of patients with unprovoked VTE who discontinued oral anticoagulation after 5–7 months of therapy, six single nucleotide polymorphisms sites were tested to determine ABO blood type using banked DNA. The main outcome was objectively proven recurrent VTE. Mean follow-up for the cohort was 4.19 years (SD 2.16). During 1,553 patient-years of follow-up, 101 events occurred in 380 non-OO patients (6.5 events per 100 patient years; 95% CI 5.3–7.7) compared to 14 events during 560 patient years of follow-up in 129 OO patients (2.5 per 100 patient years; 95% CI 1.2–3.7), the adjusted hazard ratio was 1.98 (1.2–3.8). In conclusion, non-OO blood type is associated with a statistically significant and clinically relevant increased risk of recurrent VTE following discontinuation of anticoagulant therapy for a first episode of unprovoked VTE.

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D-Dimer Levels and Risk of Recurrence Following Provoked Venous Thromboembolism: Findings from the Riete Registry

Blood ◽

10.1182/blood-2018-99-111190 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3810-3810

Author(s):

Martin Ellis ◽

Martin Mar ◽

Monreal Manuel ◽

Orly Hamburger-Avnery ◽

Alessandra Bura-Riviere ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Venous Thromboembolism ◽

Anticoagulant Therapy ◽

Conflicts Of Interest ◽

Hazard Ratio ◽

Increased Risk ◽

Risk Patients ◽

Recurrent Vte ◽

D Dimer

Abstract Background. Patients with venous thromboembolism (VTE) secondary to transient risk factors or cancer may develop VTE recurrences after discontinuing anticoagulant therapy. Identifying at-risk patients could help to guide the ideal duration of anticoagulant therapy in these patients. Methods. We used the RIETE database to assess the prognostic value of d-dimer testing after discontinuing anticoagulation to identify patients at increased risk for recurrences. The proportion of patients with raised d-dimer levels was determined and the hazard ratio (HR) for VTE recurrences compared to those with normal levels was calculated. Univariate and multivariate analyses of factors associated with VTE recurrence were performed. Results. 3 606 patients were identified in the database in April 2018: 2 590 had VTE after a transient risk factor and 1016 had a cancer. D-dimer levels were measured after discontinuing anticoagulation in 1 732 (67%) patients with transient risk factors and 732 (72%) patients with cancer-associated VTE and these patients formed the cohort in which recurrent VTE rate was calculated. D-dimers and were elevated in 551 (31.8%) of patients with a transient risk factor and were normal in 1181 (68.2%). In the cancer-associated group, d-dimers were elevated in 398 (54.3%) and normal in 334 (45.7%) patients. The adjusted hazard ratio for recurrent VTE was: 2.32 (95%CI: 1.55-3.49) in patients with transient risk factors and 2.23 (95%CI: 1.50-3.39) in those with cancer. Conclusions. Patients with raised d-dimer levels after discontinuing anticoagulant therapy for provoked or cancer-associated VTE are at increased risk for recurrent VTE and death. Future studies could target these patients for extended anticoagulation. Disclosures No relevant conflicts of interest to declare.

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Red cell distribution width is associated with incident venous thromboembolism (VTE) and case-fatality after VTE in a general population

Thrombosis and Haemostasis ◽

10.1160/th14-04-0335 ◽

2015 ◽

Vol 113 (01) ◽

pp. 193-200 ◽

Cited By ~ 16

Author(s):

Jostein Lappegård ◽

Tove Skjelbakken ◽

Sigrid Brækkan ◽

John-Bjarne Hansen ◽

Trygve S. Ellingsen

Keyword(s):

Venous Thromboembolism ◽

General Population ◽

Case Fatality ◽

Red Cell Distribution Width ◽

Red Cell ◽

Cell Distribution ◽

Distribution Width ◽

All Cause Mortality ◽

Recurrent Vte

SummaryRecent studies suggest an association between red cell distribution width (RDW) and incident venous thromboembolism (VTE). We aimed to investigate the impact of RDW on risk of incident and recurrent VTE, and case-fatality, in a general population. RDW was measured in 26,223 participants enrolled in the Tromsø Study in 1994–1995. Incident and recurrent VTE events and deaths during follow-up were registered until January 1, 2012. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). There were 647 incident VTE events during a median of 16.8 years of follow-up. Individuals with RDW in the highest quartile (RDW≥13.3%) had 50% higher risk of an incident VTE than those in the lowest quartile (RDW≤12.3%). The association was strongest for unprovoked deep-vein thrombosis (HR highest vs lowest quartile of RDW: 1.8, 95% CI 1.1–3.1). VTE patients with baseline RDW≥13.3% had 30% higher risk of all-cause mortality after the initial VTE event than VTE patients with RDW<13.3%. There were no association between RDW and risk of recurrent VTE. Our findings suggest that high RDW is a risk factor of incident VTE, and that RDW is a predictor of all-cause mortality in VTE patients.

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Personality disorders and cause-specific mortality: a nationwide study of 2 million adolescents

Psychological Medicine ◽

10.1017/s0033291720003530 ◽

2020 ◽

pp. 1-9

Author(s):

Shmuel Tiosano ◽

Lucian Laur ◽

Amir Tirosh ◽

Ariel Furer ◽

Arnon Afek ◽

...

Keyword(s):

Personality Disorders ◽

Late Adolescence ◽

Increased Risk ◽

All Cause Mortality ◽

Specific Mortality ◽

Israeli Army ◽

Study Participants ◽

Lifestyle Education ◽

Related Mortality

Abstract Background Personality disorders are prevalent in 6–10% of the population, but their risk for cause-specific mortality is unclear. The aim of the study was to assess the association between personality disorders diagnosed in late adolescence and all-cause as well as cause-specific (cardiovascular-related, external-related) mortality. Methods We performed a longitudinal study on a historical prospective cohort based on nationwide screening prior to recruitment to the Israeli army. The study participants were 16–19-year-old persons who attended the army screening (medical and cognitive, including screening for psychiatric disorders) between 1967 and 2006. Participants were followed from 1967 till 2011. Results The study included 2 051 606 subjects, of whom 1 229 252 (59.9%) were men and 822 354 (40.1%) were women, mean age 17.36 years. There were 55 508 (4.5%) men and 8237 (1.0%) women diagnosed with personality disorders. The adjusted hazard ratio (HRs) for coronary, stroke, cardiovascular, external-related causes and all-cause mortality among men with personality disorders were 1.34 (1.03–1.74), 1.82 (1.20–2.76), 1.45 (1.23–1.71), 1.41 (1.30–1.53) and 1.44 (1.36–1.51), respectively. The absolute rate difference for all-cause mortality was 56.07 and 13.19 per 105 person-years among men and women, respectively. Among women with personality disorders, the adjusted HRs for external-related causes and all-cause mortality were 2.74 (1.87–4.00) and 2.01 (1.56–2.58). Associations were already evident within 10 years of follow-up. Conclusions Personality disorder in late adolescence is associated with increased risk of cardiovascular, external- and all-cause mortality. Increased cardiovascular mortality is evident before the age of 40 years and may point to the importance of lifestyle education already in youth.

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Dietary Intake of Marine Polyunsaturated n-3 Fatty Acids and Risk of Recurrent Venous Thromboembolism

Thrombosis and Haemostasis ◽

10.1055/s-0039-1697663 ◽

2019 ◽

Vol 119 (12) ◽

pp. 2053-2063 ◽

Cited By ~ 3

Author(s):

Trond Isaksen ◽

Line H. Evensen ◽

Sigrid K. Brækkan ◽

John-Bjarne Hansen

Keyword(s):

Fatty Acids ◽

Venous Thromboembolism ◽

Dietary Intake ◽

Cox Regression ◽

Risk Of Recurrence ◽

Vein Thrombosis ◽

Hazard Ratios ◽

All Cause Mortality ◽

Recurrent Vte

Abstract Background Limited knowledge exists on the association between intake of long-chained n-3 polyunsaturated fatty acids (n-3 PUFAs) and risk of recurrence and all-cause mortality in patients with venous thromboembolism (VTE). Objectives This article investigates whether intake of marine n-3 PUFAs was associated with risk of recurrence and mortality in patients with incident VTE. Methods A total of 595 patients with incident VTE and available data on n-3 PUFA intake were derived from the Tromsø Study surveys 4 (1994–1995) and 6 (2007–2008). Weekly intake of n-3 PUFAs was categorized as low, medium, and high based on tertiles. Recurrent VTEs and all-cause mortality were registered up to December 31, 2016. Hazard ratios (HRs) were calculated using Cox regression models with the low intake category as reference. Results There were 98 recurrent VTEs and 227 deaths during follow-up. Overall, we found no association between intake of n-3 PUFAs and risk of recurrent VTE. However, inverse associations were found for high intakes in patients with unprovoked VTE (HR 0.45, 95% confidence interval [CI]: 0.20–1.01), cancer-free patients (HR 0.51, 95% CI: 0.27–0.95), and deep vein thrombosis (DVT) patients (HR 0.49, 95% CI: 0.24–0.97). The inverse associations were more evident when follow-up was restricted to the time after discontinuation of anticoagulant therapy. No association was observed between intake of n-3 PUFAs and mortality after incident VTE. Conclusion A high dietary intake of marine n-3 PUFAs was associated with lower risk of recurrent VTE after unprovoked index events, DVT, and in cancer-free patients.

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Effectiveness and safety of oral anticoagulants in the treatment of acute venous thromboembolism: A nationwide comparative cohort study in France

Thrombosis and Haemostasis ◽

10.1055/a-1731-3922 ◽

2022 ◽

Author(s):

Laurent Bertoletti ◽

Gaelle Gusto ◽

Artak Khachatryan ◽

Nadia Quignot ◽

Jose Chaves ◽

...

Keyword(s):

Venous Thromboembolism ◽

Propensity Score ◽

Conventional Therapy ◽

Proportional Hazards ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

All Cause Mortality ◽

Recurrent Vte

Introduction: Data from clinical trials indicate that direct oral anticoagulants (DOACs) are non-inferior and safer than conventional therapy (low-molecular weight heparin followed by a vitamin K antagonist [VKA]) for treating venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism (PE). This study compared the effectiveness and safety of DOACs and conventional therapy in a real-world setting. Materials and Methods: This observational study used French national claims data of adult, treatment-naïve patients diagnosed with VTE (majority PE) who were hospitalized and treated for VTE with a DOAC (apixaban or rivaroxaban) or VKAs during 2013–2018. Patients with active cancer were excluded. After propensity score matching for each DOAC-VKA comparison, risks of bleeding, recurrent VTE, and all-cause mortality were compared at 6 months. Cox proportional-hazards regression was used to estimate adjusted hazard ratios of the endpoints. Results: 58137 patients were included (10775 VKAs, 10440 apixaban, 36922 rivaroxaban). Propensity score-matched cohort sizes were 7503 for apixaban and 9179 for rivaroxaban. The hazard ratio (95% confidence interval) was significantly lower for apixaban than VKAs for bleeding requiring hospitalization (0.43 [0.32-0.59]), all-cause death (0.61 [0.51-0.74]), and first-recurrent VTE (0.67 [0.52-0.85]). The hazard ratio was also significantly lower for rivaroxaban than VKAs for all-cause death (0.63 [0.53-0.74]) but not for bleeding requiring hospitalization (0.86 [0.69-1.07]) or first-recurrent VTE (0.91 [0.74-1.13]). Conclusions: Apixaban was associated with superior safety and effectiveness than VKAs. All-cause mortality was lower in both DOACs than VKAs. Our results support recommendations to use DOACs over VKAs for the treatment of VTE.

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Venous thromboembolism and bleeding in a community setting

Thrombosis and Haemostasis ◽

10.1160/th08-06-0352 ◽

2009 ◽

Vol 101 (05) ◽

pp. 878-885 ◽

Cited By ~ 17

Author(s):

Joel Gore ◽

George Reed ◽

Darleen Lessard ◽

Luigi Pacifico ◽

Cathy Emery ◽

...

Keyword(s):

Venous Thromboembolism ◽

Total Mortality ◽

Community Setting ◽

Patient Characteristics ◽

Recurrence Rates ◽

Increased Risk ◽

History Of ◽

Recurrent Vte ◽

The Impact

SummaryBleeding is the most frequent complication of antithrombotic therapy for venous thromboembolism (VTE). However, little attention has been paid to the impact of bleeding after VTE in the community setting. The purpose of this investigation was to describe the incidence rate of bleeding after VTE, to characterize patients most at risk for bleeding, and to assess the impact of bleeding on rates of recurrent VTE and all-cause mortality. The medical records of residents of the Worcester (MA, USA) metropolitan area diagnosed with ICD-9 codes consistent with potential VTE during 1999, 2001, and 2003 were individually validated and reviewed by trained data abstracters. Clinical characteristics, acute treatment, and outcomes (including VTE recurrence rates, bleeding rates, and mortality) over follow-up (up to 3 years maximum) were evaluated. Bleeding occurred in 228 (12%) of 1,897 patients with VTE during our follow-up. Of these, 115 (58.8%) had evidence of early bleeding occurring within 30 days of VTE diagnosis. Patient characteristics associated with bleeding included impaired renal function and recent trauma. Other than a history of prior VTE, the occurrence of bleeding was the strongest predictor of recurrent VTE (hazard ratio [HR] 2.18; 95% confidence interval [CI] 1.54–3.09) and was also a predictor of total mortality (HR 1.97; 95%CI 1.57–2.47). The occur-rence of bleeding following VTE is associated with an increased risk of recurrent VTE and mortality. Future study of antithrombotic strategies for VTE should be informed by this finding. Advances that result in decreased bleeding rates may paradoxically decrease the risk of VTE recurrence.

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Right heart thrombi in pulmonary embolism

European Respiratory Journal ◽

10.1183/13993003.01044-2016 ◽

2016 ◽

Vol 48 (5) ◽

pp. 1377-1385 ◽

Cited By ~ 14

Author(s):

Deisy Barrios ◽

Vladimir Rosa-Salazar ◽

David Jiménez ◽

Raquel Morillo ◽

Alfonso Muriel ◽

...

Keyword(s):

Pulmonary Embolism ◽

Major Bleeding ◽

Prognostic Significance ◽

Right Heart ◽

Younger Age ◽

Increased Risk ◽

All Cause Mortality ◽

Oxyhaemoglobin Saturation ◽

Related Mortality

There is a lack of comprehensive data on the prevalence, predictors and prognostic significance of right heart thrombi (RHT) in pulmonary embolism.In this study of patients with pulmonary embolism from the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry, we assessed the prevalence and predictors of RHT, and the association between the presence of RHT and the outcomes of all-cause mortality, pulmonary embolism-related mortality, recurrences, and major bleeding through 30 days after initiation of pulmonary embolism treatment.Of 12 441 patients with pulmonary embolism and baseline echocardiographic data, 2.6% had RHT. The following increased the risk of RHT: younger age, previous bleeding, congestive heart failure, cancer, syncope, systolic blood pressure <100 mmHg, and arterial oxyhaemoglobin saturation <90%. Patients with RHT were significantly more likely to die from any cause (adjusted OR 2.50 (95% CI 1.62–3.84); p<0.001) and from pulmonary embolism (adjusted OR 4.29 (95% CI 2.45–7.48); p<0.001) during follow-up. RHT was associated with an increased risk of recurrence during follow-up (1.8% versus 0.7%; p=0.04). Major bleeding was similar in patients with and without RHT.In patients presenting with pulmonary embolism, RHT is relatively infrequent. Patients with RHT had a worse outcome when compared with those without RHT.

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Preliminary Investigations Showing Venous Thromboembolism Recurrence in Patients with Residual Venous Obstruction in Singaporean Population

International Journal of Angiology ◽

10.1055/s-0037-1603906 ◽

2017 ◽

Vol 26 (04) ◽

pp. 223-227

Author(s):

Chaozer Er ◽

Claudia Chong ◽

Han Chin ◽

Tay Chin ◽

Ashish Sule

Keyword(s):

Venous Thromboembolism ◽

Femoral Vein ◽

Asian Population ◽

Common Iliac Vein ◽

Venous Obstruction ◽

Diagnostic Laboratory ◽

Superficial Femoral Vein ◽

Increased Risk ◽

Recurrent Vte

AbstractThis study aims to determine the association of residual venous obstruction (RVO) with recurrent venous thromboembolism (VTE). A retrospective cohort study was conducted determining if RVO on ultrasonography is associated with recurrent VTE in a Singaporean population. The subjects were identified from the Vascular Diagnostic Laboratory patients' record of Tan Tock Seng Hospital (TTSH), Singapore between 2008 and 2013. All the patients included had RVO after 3 months of anticoagulation. Data such as age, gender, race, thrombus location, etiology, history of malignancy, thrombophilia screen, treatment duration, and follow-up were recorded for analysis. Statistical analysis was performed using Stata/SE 13.1 (StataCorp LLC). The study was approved by the National Healthcare Group Domain Specific Review Board (DSRB), Singapore. Out of the 34 patients who had RVO, 6 (17.6%) developed VTE recurrence. Patients were treated with anticoagulation for a mean time of 24.5 months. The mean follow-up time for VTE recurrence was 25.4 months. Out of the six patients who had VTE recurrence, one had common iliac vein involvement, four had superficial femoral vein and common femoral vein involvement, zero had popliteal vein involvement, and one had calf veins involvement. There was a significant association between thrombophilia (p = 0.0195) and malignancy (p = 0.020) at inclusion with the risk of recurrent VTE. The presence of RVO after 3 months of anticoagulation is likely to increase the risk of VTE recurrence. Larger studies with RVO are needed to evaluate if there is an increased risk of VTE recurrence in the Asian population.

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Epidemiology, Prevention, Diagnosis, and Management of Venous Thromboembolism in Gastrointestinal Cancers

Digestive Disease Interventions ◽

10.1055/s-0040-1716738 ◽

2020 ◽

Vol 04 (03) ◽

pp. 248-259

Author(s):

William J. Chapin ◽

Preeti Sudheendra ◽

Luis Goity ◽

Deepak Sudheendra

Keyword(s):

Venous Thromboembolism ◽

Oral Anticoagulants ◽

Vena Cava ◽

Filter Placement ◽

Diagnosis And Management ◽

Patients With Cancer ◽

Risk Of Bleeding ◽

Catheter Directed Thrombolysis ◽

Increased Risk ◽

Recurrent Vte

AbstractVenous thromboembolism (VTE) is a leading cause of cardiovascular death and is associated with significant morbidity. Patients with cancer, and gastrointestinal (GI) malignancies in particular, are at increased risk of VTE, increased risk of bleeding with VTE treatment, and increased risk of recurrent VTE compared with the general population. VTE has been shown to be a leading cause of death among patients with cancer. This review will discuss special considerations in the prevention, diagnosis, and management of VTE in patients with GI malignancies. Given the increased risk of VTE observed in ambulatory patients with GI malignancies, multiple trials have examined and demonstrated the efficacy of prophylactic anticoagulation in high-risk patients with cancer undergoing chemotherapy, particularly in patients with gastric and pancreatic cancers. Patients with GI malignancies have also played a central role in discussions of the risks and benefits of the use of direct oral anticoagulants in patients with cancers, with first-line anticoagulation options expanding to include low-molecular-weight heparin, rivaroxaban, edoxaban, and apixaban. However, there continue to be concerns regarding an increased risk of bleeding with edoxaban and rivaroxaban in patients with GI malignancies. In addition to anticoagulation, individualized risk and benefit analysis should be undertaken for interventions including inferior vena cava (IVC) filter placement and catheter-directed thrombolysis in the setting of increased risk of bleeding and recurrent VTE for patients with GI malignancies. Several unique scenarios that may be seen with GI malignancies, including incidental VTE, splanchnic vein thrombosis, IVC thrombosis, and iliac vein compression, require individualized decision making.

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