PO-98 Venous thromboembolism (VTE) as first sign of occult malignancy is associated with increased risk of recurrent VTE

SummaryAbnormalities of the Protein C (PC) pathway are found in the majority of patients with thrombophilia. ProC Global is a coagulation assay that reflects the net effect of the PC pathway by measuring the activated partial thromboplastin time (APTT) of patient and control plasma, before and after activation of endogenous PC by Protac, a snake venom. Previous studies have suggested that abnormalities in this test are associated with an increased risk of venous thromboembolism (VTE). A retrospective analysis was performed using frozen plasma samples from 140 patients with confirmed VTE to determine whether an abnormal ProC Global result (in the presence and in the absence of known abnormalities in the PC pathway) is a predictor of initial and recurrent VTE. Patients were tested for the presence of activated protein C resistance, Factor V Leiden, PC and protein S (PS) deficiency, and non-specific inhibitor positivity. Mean ProC Global results were significantly lower in patients with recurrent VTE than in patients without recurrent VTE. The association between abnormal ProC Global result and recurrent VTE showed a strong trend, before (odds ratio, OR 3.6) and after (OR 3.1) exclusion of known thrombophilic abnormalities. Patients with a first episode of idiopathic VTE also expressed significant lower ProC Global results than those with secondary VTE. After exclusion of known PC pathway abnormalities, there was a statistically significant association between abnormal ProC Global and initial idiopathic VTE (p=0.04). These results suggest that ProC Global may serve as a predictor of recurrent VTE and potentially for first episode of idiopathic VTE. ProC Global may help identify patients at increased risk of initial and recurrent VTE.

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P-selectin gene haplotypes modulate soluble P-selectin concentrations and contribute to the risk of venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th07-11-0672 ◽

2008 ◽

Vol 99 (11) ◽

pp. 899-904 ◽

Cited By ~ 15

Author(s):

Alexandra Kaider ◽

Silvia Koder ◽

Simon Panzer ◽

Ingrid Pabinger ◽

Cihan Ay ◽

...

Keyword(s):

Venous Thromboembolism ◽

Plasma Concentrations ◽

Factor V Leiden ◽

Chromosome 1 ◽

Computer Assisted ◽

Factor V Leiden Mutation ◽

Individual Snps ◽

Increased Risk ◽

Recurrent Vte ◽

Soluble P

SummaryThe cell adhesion molecule P-selectin mediates the interaction of activated platelets or endothelial cells with leukocytes. In arterial and venous thromboembolism (VTE) increased soluble P-selectin (sP-selectin) concentrations have been found, and associations of P-selectin genotypes with thrombotic disease have been proposed. We assessed the effect of four single nucleotide polymorphisms (SNPs) [one in the promoter region (c.–2123C>G) and three (S290N, c.1087G>A; D562N, c.1902G>A; T715P, c.2363A>C) in the coding region] and the calculated haplotypes in the P-selectin gene (SELP) on sP-selectin concentrations and VTE risk. The analysis was carried out in 116 high-risk patients with a history of objectively confirmed recurrent VTE and 129 age- and sex-matched healthy individuals. Haplotypes were generated using computer-assisted haplotype reconstruction with Phase 2.1. sP-selectin (μg/l) was measured by ELISA. Frequencies of all four individual SNPs were not statistically significantly different between patients and controls. Tenhaplotypes were obtained for the control population, and nine for the patient group. The most frequent haplotype among controls was CGGA (major allele at all positions) (27.8%; frequency in patients 19.0%), which was used as reference for statistical analyses. Among patients GGAA was most frequent (23.3%; frequency in controls 17.5%). Haplotypes were significantly associated with sP-selectin concentrations in patients and in controls (p<0.001 and p=0.011). Compared to CGGA some but not all haplotypes conferred an increased risk for VTE with odds ratios (ORs) between 5.4 (95% CI: 2.5–12.2) for CAGA, 3.3 (1.2–9.2) for CGAC, and 2.4 (1.3–4.7) for GGAA. All ORs remained statistically significant after adjustment for the factor V Leiden mutation, located in close proximity to SELP on chromosome 1, as well as all other established risk factors for VTE. In conclusion, SELP haplotypes modulate plasma concentrations of sP-selectin and affect the risk of recurrent VTE.

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Influence Of Antithrombin Deficiency On Symptomatic Recurrent Venous Thromboembolism (VTE) In Children: A Multicenter Cohort Study

Blood ◽

10.1182/blood.v122.21.3619.3619 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3619-3619

Author(s):

Gili Kenet ◽

Verena Limperger ◽

Neil A Goldenberg ◽

Christine Heller ◽

Susanne Holzhauer ◽

...

Keyword(s):

Multivariate Analysis ◽

Venous Thromboembolism ◽

Pediatric Patients ◽

Cox Regression ◽

Conflicts Of Interest ◽

Antithrombin Deficiency ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

At Deficiency ◽

Recurrent Vte

Abstract Objective To determine the importance of antithrombin [AT] deficiency as risk factor or predictor for fatal/non-fatal recurrent venous thromboembolism (VTE) in children. Methods In the present cohort of 874 consecutively enrolled pediatric patients with VTE aged newborn to <18 years the rate of VTE recurrence and the time to recurrence in relation to AT-deficiency [confirmed by underlying gene mutations; type 1 deficiency n=17; type 2 deficiency n=3], age and sex was determined. Twenty of 874 patients [2.4%] suffered from AT-deficiency. From the same cohort 150 VTE children carrying the heterozygous F5 G1691A mutation [F5: 17.7%] served as controls. Patients were prospectively followed for a median of 84 months. Data were pooled across participating sites to increase power and to enhance the generalisability of the data. Incidence rates were given as events per 1000 person-years. Results Of the 170 children enrolled 26 [AT n=9; F5 n=17] had recurrent VTE at a median of 15 months [95%CI: 12-36] following VTE onset: two of nine [AT] and two of 17 [F5] children suffered recurrent VTE while on anticoagulation with warfarin. The overall incidence rate of recurrence was 61.5 in patients with AT-deficiency compared to 23.5 for pediatric F5 carriers [p=0.02]. The recurrent-free survival probability is shown in the figure [logrank p-value: p=0.001]. When comparing AT patients and F5 children multivariate analysis [Cox regression] adjusted for age, sex and duration of anticoagulation treatment showed that AT deficiency [HR/95%CI: 4.1/1.8-9.4] significantly influenced the hazard for recurrent VTE. Conclusions Based on multivariate analysis, the presence of AT deficiency was associated with an increased risk of VTE recurrence. AT-deficiency in pediatric patients should be identified at VTE onset and the possible influence of intensified treatment protocols on recurrence should be studied in future prospective international studies. Condensed abstract To determine the relative importance of antithrombin deficiency or factor V (FV) mutations as risk factors for fatal/non-fatal recurrence in pediatric thromboembolism (VTE). Antithrombin deficiency influenced the hazard for recurrent VTE. Disclosures: No relevant conflicts of interest to declare.

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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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Association Between Anticoagulation Outcomes and Venous Thromboembolism History in Chronic Thromboembolic Pulmonary Hypertension

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.628284 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yong-Jian Zhu ◽

Yu-Ping Zhou ◽

Yun-Peng Wei ◽

Xi-Qi Xu ◽

Xin-Xin Yan ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Venous Thromboembolism ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Prior History ◽

Anticoagulation Treatment ◽

Increased Risk ◽

Thromboembolic Pulmonary Hypertension ◽

History Of ◽

Recurrent Vte ◽

Potential Factors

Background: The association between anticoagulation outcomes and prior history of venous thromboembolism (VTE) in chronic thromboembolic pulmonary hypertension (CTEPH) has not been established. This study aimed to compare the efficacy and safety of anticoagulation treatment in CTEPH patients with and without prior history of VTE.Methods: A total of 333 CTEPH patients prescribed anticoagulants were retrospectively included from May 2013 to April 2019. The clinical characteristics were collected at their first admission. Incidental recurrent VTE and clinically relevant bleeding were recorded during follow-up. The Cox proportional regression models were used to identify potential factors associated with recurrent VTE and clinically relevant bleeding.Results: Seventy patients (21%) without a prior history of VTE did not experience recurrent VTE during anticoagulation. Compared to CTEPH patients without a prior history of VTE, those with a prior history of VTE had an increased risk of recurrent VTE [2.27/100 person-year vs. 0/100 person-year; hazard ratio (HR), 8.92; 95% confidence interval (CI), 1.18–1142.00; P = 0.029] but a similar risk of clinically relevant bleeding (3.90/100 person-year vs. 4.59/100 person-year; HR, 0.83; 95% CI, 0.38–1.78; P = 0.623). Multivariate Cox analyses suggested that a prior history of VTE and interruption of anticoagulation treatments were significantly associated with an increased risk of recurrent VTE, while anemia and glucocorticoid use were significantly associated with a higher risk of clinically relevant bleeding.Conclusions: This study is the first to reveal that a prior history of VTE significantly increases the risk of recurrent VTE in CTEPH patients during anticoagulation treatment. This finding should be further evaluated in prospective studies.

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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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Treatment of venous thromboembolism with rivaroxaban in relation to body weight

Thrombosis and Haemostasis ◽

10.1160/th16-02-0087 ◽

2016 ◽

Vol 116 (10) ◽

pp. 739-746 ◽

Cited By ~ 23

Author(s):

Maria C. Vedovati ◽

Antoni Riera-Mestre ◽

Martin H. Prins ◽

Katharina Mueller ◽

Alexander T. Cohen ◽

...

Keyword(s):

Venous Thromboembolism ◽

Treatment Period ◽

Major Bleeding ◽

Proportional Hazards Model ◽

Cox Proportional Hazards Model ◽

Fixed Dose ◽

Bleeding Events ◽

Hazard Ratios ◽

Increased Risk ◽

Recurrent Vte

SummaryThe pharmacokinetics of oral rivaroxaban are highly predictable and only affected to a limited extent by bodyweight; therefore, dose adjustments for bodyweight are not required. However, this raises concerns among physicians for potential under- or overdosing. This substudy of the randomised EINSTEIN DVT and EINSTEIN PE trials, which compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy, aimed to determine the incidence of major bleeding in patients with a low bodyweight and recurrent venous thromboembolism (VTE) in patients with a high bodyweight during rivaroxaban or enoxaparin/VKA therapy. More than 8,000 patients with objectively diagnosed deepvein thrombosis or pulmonary embolism were included. Adjusted hazard ratios for recurrent VTE and bleeding were calculated using the Cox proportional hazards model. Analyses were performed for both the first 21 days of treatment and the whole treatment period. For rivaroxaban recipients, there was no association between bodyweight or body mass index (BMI) and risk of recurrent VTE (ptrend=0.87 and 0.62, respectively), major bleeding (ptrend=0.24 and 0.36, respectively) or clinically relevant bleeding (ptrend=0.17 and 0.63, respectively). Major bleeding events were numerically lower in rivaroxaban patients across all bodyweight and BMI categories. Hazard ratios for rivaroxaban vs enoxaparin/VKA were similar in all bodyweight and BMI categories, both during the first 21 days and the whole treatment period. The fixed-dose rivaroxaban regimen is not associated with an increased risk of major bleeding or recurrent VTE in patients with either a low or high bodyweight. A high BMI was not associated with an increased risk of recurrent VTE during anticoagulation.Note: This study was presented at the 25th Congress of the International Society on Thrombosis and Haemostasis; June, 2015, Toronto, Canada. Trial registration: EINSTEIN DVT (NCT00440193), EINSTEIN PE (NCT00439777).

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

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0039-1697682 ◽

2019 ◽

Vol 45 (08) ◽

pp. 793-801 ◽

Cited By ~ 5

Author(s):

Behnood Bikdeli ◽

David Jiménez ◽

Guadalupe Garcia-Tsao ◽

Raquel Barba ◽

Carme Font ◽

...

Keyword(s):

Venous Thromboembolism ◽

Hazard Ratio ◽

Risk Of Bleeding ◽

Fatal Bleeding ◽

Increased Risk ◽

All Cause Mortality ◽

Recurrent Vte ◽

One Year ◽

Related Mortality

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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Risk of recurrent venous thromboembolism in COPD patients: results from a prospective cohort study

European Respiratory Journal ◽

10.1183/13993003.00094-2017 ◽

2017 ◽

Vol 50 (1) ◽

pp. 1700094 ◽

Cited By ~ 3

Author(s):

Raphael Le Mao ◽

Cécile Tromeur ◽

Amélie Bazire ◽

Maelenn Gouillou ◽

Marie Guegan ◽

...

Keyword(s):

Venous Thromboembolism ◽

Prospective Cohort ◽

Multivariate Analyses ◽

Anticoagulation Therapy ◽

Secondary Outcome ◽

Risk Of Death ◽

Copd Patients ◽

Increased Risk ◽

Recurrent Venous Thromboembolism ◽

Recurrent Vte

We aimed to assess the risk of recurrent venous thromboembolism (VTE) in patients with chronic obstructive pulmonary disease (COPD) following cessation of anticoagulation therapy.In a prospective cohort of 1468 patients with a documented episode of VTE, followed for up to 5 years after cessation of anticoagulation therapy, the diagnosis of COPD was confirmed in 136. The main outcome was recurrent VTE. The secondary outcome was overall mortality. Univariate and multivariate analyses were performed to identify the risk factors of recurrence.Of the 1468 patients included, recurrent VTE was observed in 306 (34 with COPD and 272 without) during a median follow-up period of 36.5 months. The incidence rate of recurrent VTE was 9.1% (95% CI 6.5–12.8) for COPD patients and 7.0% (95% CI 6.2–7.9) for non-COPD patients. COPD was not associated with an increased risk of VTE recurrence on univariate or multivariate analyses (hazard ratio: 1.0 (95% CI 0.7–1.4)). The risk of death, adjusted for demographic and clinical characteristics, showed no increase in COPD patients, as compared to non-COPD patients.In patients with COPD who had an acute episode of VTE, the risk of recurrent VTE was not any higher than that in non-COPD patients.

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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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