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

Blood ◽  
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.

Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4432-4436 ◽  
Author(s):  
Clive Kearon ◽  
Jim A. Julian ◽  
Michael J. Kovacs ◽  
David R. Anderson ◽  
Philip Wells ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Warfarin Therapy ◽  
Factor V Leiden ◽  
International Normalized Ratio ◽  
Antiphospholipid Antibody ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Recurrent Venous Thromboembolism ◽  
Prothrombin Gene Mutation ◽  
Recurrent Vte

Abstract We sought to determine whether thrombophilic defects increase recurrent venous thromboembolism (VTE) during warfarin therapy. Six hundred sixty-one patients with unprovoked VTE who were randomized to extended low-intensity (international normalized ratio [INR], 1.5-1.9) or conventional-intensity (INR, 2.0-3.0) anticoagulant therapy were tested for thrombophilia and followed for a mean of 2.3 years. One or more thrombophilic defects were present in 42% of patients. The overall rate of recurrent VTE was 0.9% per patient-year. Recurrent VTE was not increased in the presence of factor V Leiden (hazard ratio [HR], 0.7; 95% CI, 0.2-2.6); the 20210G>A prothrombin gene mutation (HR, 0); antithrombin deficiency (HR, 0); elevated factor VIII (HR, 0.7; 95% CI, 0.1-5.4); elevated factor XI (HR, 0.7; 95% CI, 0.1-5.0), or elevated homocysteine (HR, 0.7; 95% CI, 0.1-5.3), but showed a trend to an increase with an antiphospholipid antibody (HR, 2.9; 95% CI, 0.8-10.5). Compared with patients with no thrombophilic defects, the rate of recurrence was not increased in the presence of one (HR, 0.7; 95% CI, 0.2-2.3) or more than one (HR, 0.7; 95% CI, 0.2-3.4) defect. We conclude that single or multiple thrombophilic defects are not associated with a higher risk of recurrent VTE during warfarin therapy.

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

2013 ◽  
Vol 110 (12) ◽  
pp. 1172-1179 ◽  
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.

scholarly journals Postoperative Venous Thromboembolism in Children Is Increased in Setting of Cancer or Infection

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2391-2391
Author(s):  
Harold J. Leraas ◽  
Jina Kim ◽  
Zhifei Sun ◽  
Uttara P. Nag ◽  
Brian D. Ezekian ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Venous Thromboembolism ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Significant Risk ◽  
The United States ◽  
Improvement Program ◽  
Thrombotic Risk ◽  
Factors Associated

Abstract Background: Venous thromboembolism (VTE) is an uncommon but clinically significant postoperative complication in children. Incidence of VTE in pediatric patients ranges from 34-58 per 10,000 hospitalized children1. Due to rarity of these events, there is limited information about the factors predisposing children to VTE after surgery. We queried a national surgical database to identify risks and outcomes associated with VTE in pediatric surgical patients. Methods: The National Surgical Quality Improvement Program-Pediatric (NSQIP) is a prospectively collected database that records pediatric surgical information, surgical approaches, and 30 day patient outcomes. The database was queried for the years 2012-2013 to identify pediatric patients (age < 18) who had received surgical intervention and were diagnosed with postoperative VTE. Because of their separate coding in NSQIP, we defined VTE as including venous thromboembolism, or pulmonary embolism (PE) diagnosed radiographically within 30 days of operation. To reduce non-random differences between patients we used propensity scores based on age, sex, race, BMI, and ASA classification to match patients in a 1:2 ratio using the nearest neighbor method. Using univariate and multivariate analysis, we identified preoperative risk factors associated with VTE. Results: In total, 130 patients were identified who developed VTE postoperatively (VTE n=122, PE n=7, BOTH PE + VTE n= 1) from this database of 114,395 patients. There were 104 patients with VTE that also had complete entries and were subsequently analyzed in this study. Surgical specialties treating patients in this analysis included cardiothoracic surgery, general surgery, neurosurgery, orthopedic surgery, otolaryngology, plastic surgery, and urology. Eighty-one unique operative CPT codes were identified for patients with VTE. Patients who developed VTE had increased operative time, anesthesia time, and total length of stay (all p < 0.001). Multivariate analysis demonstrated that pneumonia (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.3 - 2.29), Central Line Associated Bloodstream Infection (CLABSI) (OR 1.69, 95% CI 1.18 - 2.42), sepsis (OR 1.47, 95% CI 1.18 - 1.82), septic shock (OR 1.36, 95% CI 1.06 - 1.75), and current solid or hematologic malignancy or active treatment of malignancy (OR 1.30, 95% CI 1.08 - 1.58) were all statistically significant risk factors associated with development of VTE (all p < 0.05). Conclusions: Postoperative VTE risk is significantly increased in children with malignancy or severe infections. Further research is needed to understand the mechanism between malignancy, systemic inflammation, and VTE risk in children. These findings may help to identify patients in need of prophylactic treatment in order to reduce postoperative thrombotic risk in pediatric patients. References: 1. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics. 2009;124(4):1001-1008. Disclosures No relevant conflicts of interest to declare.

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

Blood ◽  
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.

scholarly journals Association of Risk of Incident and Recurrent Venous Thromboembolism with Oral Glucocorticoid Treatment

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 420-420
Author(s):  
Fernanda Andrade Orsi ◽  
Willem M Lijfering ◽  
Geert-Jan Geersing ◽  
Frits Richard Rosendaal ◽  
Olaf Dekkers ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Treatment Strategies ◽  
Case Series ◽  
Fold Increase ◽  
Glucocorticoid Treatment ◽  
Oral Glucocorticoid ◽  
Recurrent Vte ◽  
Oral Glucocorticoids

Abstract Glucocorticoids are potent anti-inflammatory drugs used for a variety of chronic diseases and acute conditions that, unfortunately, can also cause severe adverse events. Venous thromboembolism (VTE) has recently been added to the list of clinical complications associated with glucocorticoids. Epidemiological studies reported that the risk for first VTE is increased by 2 to 3-fold with the use of glucocorticoids. However, several confounders may account for the reported association and whether glucocorticoid use increases the risk of recurrent VTE is unknown. To address the issue of confounding, we determined the frequency of a first VTE event associated with the use of oral glucocorticoids employing the self-controlled case-series (SCCS) method. With SCCS every individual is contrasted with him or herself thereby eliminating fixed confounders such as age, sex or chronic comorbidity. In addition, we evaluated the effect of oral glucocorticoids on the risk of recurrent VTE in a cohort design. Patients with VTE from the MEGA study were individually linked to the Dutch Foundation for Pharmaceutical Statistics (SFK). Prescriptions of oral glucocorticoids in the period of the MEGA study were identified. The risk for the first VTE was estimated using SCCS method and conditional Poisson regression. The association between oral glucocorticoids and recurrent VTE was examined using age and sex adjusted Cox regression models. A total of 2547 patients could be linked to the SFK data register, from those 363 received at least one outpatient prescription of oral glucocorticoids. The risk for a first VTE event was 3.5-fold higher in the aggregated period of oral glucocorticoid treatment as compared with baseline periods (incident rate ratio [IRR] 3.5, 95% confidence interval [CI] 2.6-4.8). IRR of a first VTE event was 2.5 (95% CI, 1.1- 5.7) in the week before treatment started, 5.3 (95% CI, 2.9 - 9.5) during the first 7 days with treatment, 3.7 (95% CI, 2.6 - 5.2) until six months with treatment and 1.6 (95% CI, 0.8 - 3.1) after 6 months with oral glucocorticoids, as compared with the baseline period. A dose-dependent relationship between oral glucocorticoid treatment and VTE risk was observed as the IRR increased from 3.4 (95% CI, 2.3 - 5.0) with 30-day cumulative doses below 300mg to 4.9 (95% CI, 1.7 - 14.0) with 30-day cumulative doses above 2000mg, as compared with baseline periods. IRRs for DVT (3.9; 95% CI, 2.9 - 9.5) and PE (3.1; 95% CI, 2.0 - 4.9) were similar and IRR for unprovoked VTE (2.4; 95% CI, 1.3 - 4.7) was lower than the IRR for provoked VTE (4.2; 95% CI, 2.9 - 6.0). The rates of recurrent VTE were elevated in patients with unprovoked VTE and in those who had their first VTE during a period of oral glucocorticoid treatment, either if the first event was otherwise classified as provoked or unprovoked. The adjusted HR for recurrent VTE was 1.6 (95% CI, 1.2 - 2.0) in patients with unprovoked first VTE not using oral glucocorticoids at the time of their first event, 2.1 (95% CI, 1.2 - 3.8) in those who had a provoked first VTE while using oral glucocorticoids and 2.3 (95% CI, 1.2 - 7.0) in those with an unprovoked first VTE while using the drug, as compared with patients with a provoked first event not using oral glucocorticoids at the time of their first event. The risk for recurrent VTE was 2.7-fold increased (95% CI, 1.6 - 4.8) during glucocorticoid treatment periods as compared to baseline periods. We conclude that patients receiving oral glucocorticoids had an approximately three-fold increase in the risk for first and recurrent VTE. The observed risk for VTE was partly associated with the underlying disease (preexposure period) and increased further after oral glucocorticoids were prescribed. These results underscore that treatment strategies to prevent first and recurrent VTE in patients treated with oral glucocorticoids are needed. Disclosures No relevant conflicts of interest to declare.

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

2017 ◽  
Vol 50 (1) ◽  
pp. 1700094 ◽  
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.

Homozygosity in the Single Nucleotide Polymorphism Ser128Arg in the E-Selectin Gene Is Associated with Recurrent Venous Thromboembolism.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4086-4086
Author(s):  
Gregor Hron ◽  
Bernd Jilma ◽  
Claudia L. Marsik ◽  
Georg Endler ◽  
Sabine Eichinger ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Venous Thromboembolism ◽  
Cox Regression ◽  
Factor V Leiden ◽  
Hazard Ratio ◽  
Rank Test ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Recurrent Venous Thromboembolism ◽  
Recurrent Vte

Abstract Objective: The single nucleotide polymorphism (SNP) Ser128Arg in the E-selectin gene is over-represented in certain patient populations with atherosclerosis or restenosis. As this SNP enhances tissue factor triggered coagulation in humans during systemic inflammation, we hypothesized that it may also predispose for the development of recurrent venous thromboembolism (VTE). Methods and Results: Patients (n=585) after first VTE were prospectively followed up for recurrent, objectively documented, symptomatic VTE. Patients with secondary VTE, homozygous Factor V Leiden, natural inhibitor deficiencies, lupus anticoagulant, or long term anticoagulation were excluded. The S128R SNP was genotyped by mutagenically separated PCR. One-hundred and two patients (17.4%) were heterozygous and 11 were homozygous (1.9%) for the Ser128Arg mutation. Ninety patients (15.4%) suffered from recurrent VTE during follow-up. Homozygosity for the Ser128Arg SNP increased the cumulative likelihood particularly for early recurrent VTE (log rank test p&lt;0.05) and was an independent predictor of recurrent VTE (hazard ratio: 4.1; 95% CI 1.5–11.4) in a multivariate Cox Regression model. In contrast, heterozygosity for the polymorphism was associated with an unaltered hazard ratio (HR: 1.1; 95% CI 0.6–1.9) for recurrent VTE. Conclusion: Homozygosity for the S128R E-selectin allele appears to increase the risk for recurrent VTE several-fold, and -if confirmed- may represent a novel risk factor for recurrent VTE. These results also expand our knowledge on the association of this SNP with thrombotic disorders.

Hypofibrinolysis and the Risk of Recurrent Venous Thromboembolism: A Prospective Cohort Study,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3331-3331
Author(s):  
Sabine Eichinger ◽  
Ludwig Traby ◽  
Georg Heinze ◽  
Marietta Kollars ◽  
Lisbeth Eischer ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Conflicts Of Interest ◽  
Factor V Leiden ◽  
Cox Proportional Hazards Model ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Clotting Factors ◽  
Increased Risk ◽  
Recurrent Vte

Abstract Abstract 3331 Hypercoagulability reflected by enhanced activity of clotting factors or a natural inhibitor deficiency is a risk factor of venous thromboembolism (VTE). Whether defects in the fibrinolytic system confer an increased risk of VTE is unclear. We assessed the relationship between fibrinolytic system activity (reflected by clot lysis time [CLT]) and the risk of recurrent VTE. We followed 704 patients (378 women; mean age 48 years) with a first unprovoked VTE for an average of 46 months after anticoagulation withdrawal. Patients with a natural coagulation inhibitor deficiency, lupus anticoagulant, cancer, female hormone use, homozygosity or double heterozygosity for factor V Leiden or prothrombin mutation, or requirement for indefinite anticoagulation were excluded. The fibrinolytic potential was assessed using a plasma based clot-lysis assay according to Lisman et al. (1). A tissue factor-induced clot was lysed by adding tissue-type plasminogen activator and the optical density was measured at 405 nm in an absorbance microplate reader every 30 seconds in order to get a clot-lysis turbidity profile. Study end point was symptomatic recurrent VTE. 135 (19%) patients had recurrent VTE. Recurrence was unprovoked in 117 patients and was more frequent in men (97/326, 29.8%) than in women (38/378, 10.1%). When CLT was entered as continuous variable in a Cox proportional hazards model, hazard ratio (HR) for recurrence was 1.13 (95% CI 1.02–1.25; p=0.02) for each 10 minutes prolongation. The HR for recurrence was 1.11 (95% CI 1.11–1.24; p=0.046) after adjustment for age and 1.08 (95% CI 0.98–1.20; p=0.13) after additional adjustment for sex. After 5 years, the likelihood of recurrence was 23.8% (95% CI 19.3%-28.3%) in patients with a CLT longer than 63.5 minutes (25th percentile) as compared with 14.1% (95% CI 7.4%-20.8%; p=0.04) among those with a shorter CLT. Men and women differed with regard to CLT (76.1±16.2 vs. 71.5±13.6 sec, p<0.001). After adjustment for age, the HR was 1.04 (95% CI 0.92–1.18; p=0.54) among men and 1.14 (95% CI 0.93–1.14; p=0.22) among women. Hypofibrinolysis confers an increased risk of recurrent VTE. The effect was more pronounced in women than in men. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Prolonged Anticoagulation with Rivaroxaban on Provoked Venous Thromboembolism Recurrence: The Improve-VTE Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1241-1241
Author(s):  
Craig I. Coleman ◽  
Alexander G. Turpie ◽  
Thomas J. Bunz ◽  
Jan Beyer-Westendorf ◽  
William L Baker
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Research Funding ◽  
Index Date ◽  
Cox Regression ◽  
Recurrent Thrombosis ◽  
Increased Risk ◽  
Recurrent Vte ◽  
A Minor

Abstract Background: The optimal duration of anticoagulation following an incident provoked venous thromboembolism (VTE) remains unclear. Two randomized trials have shown extended duration rivaroxaban use in patients experiencing an unprovoked or provoked VTE can reduce patients' risk of recurrent thrombosis without a significant increased risk of major bleeding compared to placebo or aspirin. Objectives: We sought to evaluate the real-world effectiveness and safety of prolonged anticoagulation with rivaroxaban following an incident provoked VTE. Methods: Using claims data from the US Truven MarketScan databases from November 1, 2012 through March 31, 2017, we identified adult patients with a primary discharge diagnosis of VTE (deep vein thrombosis and/or pulmonary embolism) during a hospitalization or emergency department visit, who had a provoking (major or minor, persistent or transient) risk factor, at least 3-months of continuous rivaroxaban treatment and ≥12-months of continuous medical and prescription insurance benefits prior to their incident VTE. Patients were categorized as either continuing rivaroxaban or discontinuing anticoagulation (no anticoagulation or antiplatelet agents, with or without aspirin) after the initial 3-months of rivaroxaban treatment (index date). Differences in baseline covariates between cohorts were adjusted for using inverse probability-of-treatment weights (IPTW) based on propensity-scores (residual standardized differences <0.1 achieved for all covariates after adjustment). Study endpoints included recurrent VTE and major bleeding (per the Cunningham algorithm). Patients were followed until occurrence of an endpoint, insurance disenrollment or up to 12-months post-index date. The incidences of recurrent VTE or major bleeding were compared between cohorts using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup analyses were performed for each endpoint according to whether patients had a major persisting (i.e. cancer), minor persisting (i.e. inflammatory bowel disease, lower extremity paralysis, heart failure, stage III or worse chronic kidney disease, hereditary or acquired thrombophilia), minor transient (i.e. admitted to hospital for ≥3-consecutive days in past 3-months, hormonal therapy, pregnancy or puerperium, leg injury with impaired mobility) or major transient risk factor (i.e. major surgery or trauma). Results: Among patients experiencing an incident provoked VTE and treated with rivaroxaban for the first 3-months (N=4,990), continued rivaroxaban use beyond 3-months [median (25%, 75% range) duration of additional rivaroxaban use = 3 (2, 5) months] was associated with a 44% lower hazard of recurrent VTE without significantly altering major bleeding risk when compared to anticoagulation discontinuation with or without aspirin use (Table). The highest risk of recurrent thrombosis following provoked VTE (3.1% in the discontinued anticoagulation cohort) appeared to occur in patients with a minor persisting risk factor; with continued rivaroxaban use associated with a significant 73% reduction in recurrent VTE. Conclusions: Although the absolute incidence of recurrence was low, our study suggests continuing rivaroxaban after the initial 3-month period was associated with a decreased risk of recurrent VTE, particularly in those with a minor persisting risk factor. The observed reduction in recurrent VTE with prolonged rivaroxaban use was not associated with a significantly increased risk of major bleeding. Disclosures Coleman: Bayer AG: Consultancy, Honoraria, Research Funding; Janssen Scientific Affairs LLC: Consultancy, Honoraria, Research Funding. Turpie:Bayer AG: Consultancy, Honoraria, Research Funding; Janssen Scientific Affairs LLC: Consultancy, Speakers Bureau. Beyer-Westendorf:Boehringer-Ingelheim: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bayer: Honoraria, Research Funding.

The Risk of Recurrent Venous Thromboembolism in Carriers and Non-carriers of the G1691A Allele in the Coagulation Factor V Gene and the G20210A Allele in the Prothrombin Gene

1999 ◽  
Vol 81 (05) ◽  
pp. 684-689 ◽  
Author(s):  
Sam Schulman ◽  
Margareta Sten-Linder ◽  
Björn Wiman ◽  
Nils Egberg ◽  
Hans Johnsson ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Coagulation Factor ◽  
Factor V ◽  
Increased Risk ◽  
Recurrent Venous Thromboembolism ◽  
Coagulation Factor V ◽  
Factor V Gene ◽  
Prothrombin Gene ◽  
V Gene ◽  
Recurrent Vte

SummaryThe results concerning the risk of recurrent venous thromboembolism (VTE) in carriers of the G1691A mutation in the coagulation factor V gene are not consistent and this risk in carriers of the G20210A polymorphism in the prothrombin gene has hitherto not been reported. We followed 534 patients for 48 months after their first episode of objectively documented VTE. The prevalence of the G1691A allele in 467 (87.5%) of the patients and in 207 controls was 25.3% and 8.2%, respectively, in heterozygote form and 2.4% and 0.5%, respectively, in homozygote form. The adjusted odds ratio (OR) for the first VTE was 4.4 (95% CI 2.6-7.8). The risk of recurrent VTE in heterozygotes was not statistically different from non-carriers (17.8% vs 17.6%), with 85% power to detect a hazard ratio of 2.35. Homozygotes had a significantly increased risk (p = 0.036) of recurrent VTE. The prevalence of the G20210A allele in 456 patients and 207 controls was 6.1% and 1.4%, respectively. The adjusted OR was 4.6 (95% CI 1.6-19.3) for the first VTE in 28 carriers of this polymorphism. The risk of recurrent VTE for these was not statistically different from non-carriers with an OR of 0.9 (95% CI 0.2-2.9).

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