Risk of Recurrence after a First Episode of Symptomatic Venous Thromboembolism Provoked by a Transient Risk Factor: A Systematic Review

2011 ◽  
Vol 40 (3) ◽  
pp. 360-361
Author(s):  
Deborah Vinton
2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Giustozzi ◽  
S Barco ◽  
L Valerio ◽  
F A Klok ◽  
M C Vedovati ◽  
...  

Abstract Introduction The interaction between sex and specific provoking risk factors for venous thromboembolism (VTE) may influence initial presentation and prognosis. Purpose We investigated the impact of sex on the risk of recurrence across subgroups of patients with first VTE classified according to baseline risk factors. Methods PREFER in VTE was an international, non-interventional registry (2013–2015) including patients with a first episode of acute symptomatic objectively diagnosed VTE. We studied the risk of recurrence in patients classified according to baseline provoking risk factors for VTE consisted of i) major transient (major surgery/trauma, >5 days in bed), ii) minor transient (pregnancy or puerperium, estroprogestinic therapy, prolonged immobilization, current infection or bone fracture/soft tissue trauma); iii) unprovoked events, iv) active cancer-associated VTE. Results A total of 3,455 patients diagnosed with first acute VTE were identified, of whom 1,623 (47%) were women. The percentage of patients with a major transient risk factor was 22.2% among women and 19.7% among men. Minor transient risk factors were present in 21.3% and 12.4%, unprovoked VTE in 51.6% and 61.6%, cancer-associated VTE in 4.9% of women and 6.3% of men, respectively. The proportions of cases treated with Vitamin-K antagonists (VKAs) and direct oral anticoagulants (DOACs) were similar between sexes. Median length of treatment of VKAs was 181.5 and 182.0 days and of DOACs was 113.0 and 155.0 days in women and men, respectively. At 12-months of follow-up, VTE recurrence was reported in 74 (4.8%) women and 80 (4.5%) men. Table 1 shows the sex-specific proportion of recurrences by VTE risk factor categories. Table 1 Major Transient (n=722) Minor transient (n=573) Cancer-associated (n=195) Unprovoked (1965) Women (361) Men (361) OR (95% CI) Women (346) Men (227) OR (95% CI) Women (79) Men (116) OR (95% CI) Women (837) Men (1128) OR (95% CI) One-year follow-up, n (N%)   Recurrent VTE, 21 (6.2) 10 (2.9) 0.46 (0.2; 0.9) 9 (2.7) 12 (5.4) 2.09 (0.9; 5.0) 6 (8.0) 5 (4.5) 0.54 (0.2; 1.9) 38 (4.7) 53 (4.7) 1.03 (0.7; 1.6)   Major bleeding, 6 (1.8) 5 (1.5) 0.83 (0.3; 2.7) 5 (1.5) 1 (0.5) 0.30 (0.1; 2.6) 1 (1.3) 3 (2.7) 2.07 (0.2; 20) 10 (1.2) 15 (1.4) 1.11 (0.6; 2.4)   All-cause death, 37 (10.2) 31 (8.5) 0.82 (0.5; 1.4) 10 (2.9) 14 (6.2) 2.21 (0.9; 5.1) 26 (32.9) 49 (42.2) 1.49 (0.8; 2.7) 33 (3.9) 30 (2.7) 0.66 (0.4; 1.1) Conclusions The proportion of patients with recurrent VTE events after first acute symptomatic VTE provoked by transient risk factors was not negligible during the first year of follow-up during in both women and men. These results may have implications on the decision whether to consider extended anticoagulant therapy in selected patients with provoked events. Acknowledgement/Funding This study was funded by Daiichi Sankyo.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3029-3029
Author(s):  
Alfonso Iorio ◽  
Esmeralda Filippucci ◽  
Maura Marcucci ◽  
Clive Kearon ◽  
Gualtiero Palareti

Abstract Background: Venous thromboembolism (VTE) has a tendency to recur after anticoagulation is stopped. The optimal duration of anticoagulation is influenced by the risk of recurrence: indefinite anticoagulation is recommended after a first VTE associated with a persistent and strong risk factor (e.g. cancer), whereas three months of anticoagulation is adequate if VTE was provoked by a transient risk factor (e.g. surgery). The optimal duration of anticoagulation after a first unprovoked VTE is, however, still a matter of debate. An attractive approach is to identify subgroups of patients with unprovoked VTE who have a high risk of recurrence and treat them with prolonged anticoagulation, and subgroups with a lower risk of recurrence and treat them for only three months. A critical issue, therefore, is to determine a cut-off value for risk of recurrence that is low enough to justify stopping anticoagulant therapy at three months (i.e., a rate of recurrence that is acceptable to patients and physicians). We propose that the rate of recurrence after VTE that was provoked by a transient risk factor represents such a value. Aim of the study: To accurately estimate the risk of recurrence in patients with VTE provoked by a transient risk factor who have completed at least three months of anticoagulant therapy. Materials and Methods: Medline, Embase and Cochrane Collaboration Registry of Randomized Trials were searched for any studies reporting the recurrence rate of VTE after a first episode of VTE associated with a transient risk factor (surgery, trauma, plaster, bed rest, pregnancy, puerperium, hormone treatment). The references of retrieved articles were scanned for any additional relevant studies. Studies were included if enrolling patients met the following criteria: a first episode of VTE provoked by a transient risk factor; a course of at least three months of oral anticoagulant therapy; a follow up of 12 or 24 months after treatment discontinuation with assessment of VTE recurrence rate. Recurrence rate, or data that allowed its calculation, needed to be reported. An overall estimate of the recurrence rate was calculated following Laird (Stats Med 1990), having predefined to use a fixed-effect model if no heterogeneity was found among the studies or a random-effect model otherwise. The inverse variance method was used to calculate weights for the studies. Results: The literature search yield 1089 references. After careful scanning of the potentially relevant papers, 15 papers were included in the final analysis. All studies except one were prospective. 12/15 and 11/15 studies reported data about the recurrence rate at 12 and 24 months, respectively. Overall there were 106 events among of 2217 patients at 12 months and 160 events among 2321 patients at 24 months. The pooled recurrence rate was 4.0% (95% C.I. 3.0%–5.2%) at 12 months and 6.7% (95% C.I. 5.2%–8.6%) at 24 months. Conclusion: The cumulative risk of recurrence in patients with VTE provoked by a reversible risk factor is 6.7% (95% C.I. 5.2%–8.6%) two years after anticoagulant withdrawal. We suggest that it acceptable to stop anticoagulant therapy after three months in subgroups of patients with unprovoked VTE who have been shown to have a risk of recurrence that is similar to, or lower than, this rate.


2010 ◽  
Vol 170 (19) ◽  
Author(s):  
Alfonso Iorio ◽  
Clive Kearon ◽  
Esmeralda Filippucci ◽  
Maura Marcucci ◽  
Ana Macura ◽  
...  

2004 ◽  
Vol 2 (5) ◽  
pp. 743-749 ◽  
Author(s):  
C. Kearon ◽  
J. S. Ginsberg ◽  
D. R. Anderson ◽  
M. J. Kovacs ◽  
P. Wells ◽  
...  

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3348-3348
Author(s):  
Luis Fernando Bittar ◽  
Bruna Mazetto Fonseca ◽  
Silmara Lima Montalvão ◽  
Fernanda Loureiro de Andrade Orsi ◽  
Erich V de Paula ◽  
...  

Abstract Abstract 3348 Introduction: Venous thromboembolism (VTE) is a multifactorial disease, and increased levels of coagulation factor VIII (FVIII) has been demonstrated as risk factor for first and recurrent episodes of VTE. Some authors reported that these high levels of FVIII were still persistent after 4 years of the episode, but median follow-up in these studies are relatively short. The aim of the study was investigate if after a long-term follow-up of 4–15 years (median of 10 years), patients with high levels of FVIII after anticoagulant treatment still showed this alteration. Design and Methods: Previously, we selected 174 adult patients with a first episode of acute VTE between January 1990 and September 2004. One hundred seventy four healthy adult individuals selected from blood donors were chosen as controls, from the same geographic area of origin. Of this group of VTE patients, 68 patients with plasma FVIII: C levels above the 90th percentile were selected. FVIII levels (FVIII:C) were measured by a one-stage clotting assay with FVIII-deficient plasma in duplicate in an automated coagulometer. Levels were measured twice, in 2004 and then in 2011. C-reactive protein (CRP) levels were determined in the same samples by a nephelometric method to evaluate the influence of inflammation on FVIII levels. For individuals with CRP values higher than 1mg/dL, an additional blood sample was analyzed. High FVIII levels were only considered for further analysis when in the presence of normal CRP levels. The presence of post-thrombotic syndrome (PTS) was evaluated and classified clinically by the Clinical-Etiologic-Anatomic-Pathophysiologic (CEAP) classification System. Results: 68 patients with VTE and high levels of FVIII (19M:49F) with a median age of 47 years (range 20–70) were included in the study. The control group consisted of 59 subjects (42M:17F) with a median age of 35 years (range 21–56 years). VTE was spontaneous in 26 (38.2%) patients and secondary to an acquired risk factor in 61.8%. In the 1st evaluation, in 2004, patients with VTE had higher plasma levels of FVIII:C (median 235.8 IU/dL vs. 127.0 IU/dL; p<0.001) compared to controls. In 2011, seven years after the first evaluation and after a median follow-up of 10 years after the first VTE episode, this difference was still present (median 144.6 IU/dL vs. 96.4 IU/dL; p<0.001). Patients with severe PTS (167 IU/dL) showed higher plasma levels of FVIII when compared with patients without PTS (median 141.4 IU/dL), mild PTS patients (median 142.8 IU/dL), and moderate PTS patients (median 143.2); p=0.04. Conclusions: Our results show that even after a median of 10 years of VTE, patients still have increased levels of FVIII. Moreover, there seems to be a relationship between severe post-thrombotic syndrome and increased plasma levels of FVIII. Disclosures: No relevant conflicts of interest to declare.


Hematology ◽  
2004 ◽  
Vol 2004 (1) ◽  
pp. 424-438 ◽  
Author(s):  
Jeffrey I. Weitz ◽  
Saskia Middeldorp ◽  
William Geerts ◽  
John A. Heit

Abstract Venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, is the result of an imbalance among procoagulant, anticoagulant and profibrinolytic processes. This imbalance reflects a complex interplay between genetic and environmental or acquired risk factors. Genetic thrombophilic defects influence the risk of a first episode of thrombosis. How these defects influence the risk of recurrence in patients whose first episode of venous thromboembolism was unprovoked is less certain. Thus, when anticoagulants are stopped, patients with unprovoked venous thromboembolism have a risk of recurrence of at least 7% to 10% per year, even in the absence of an underlying thrombophilic defect. Consequently, there is a trend toward longer durations of anticoagulation therapy for these patients, which is problematic given the limitation of existing anticoagulants. This chapter provides an overview of the thrombophilic defects and how they influence the risk of venous thromboembolism. The chapter also details advances in anticoagulant therapy, focusing on new inhibitors of factor Xa and thrombin. In Section I, Dr. Saskia Middeldorp describes the various thrombophilic defects and reviews their relative importance in the pathogenesis of a first episode of venous thromboembolism. She then discusses the influence of these defects on the risk of recurrent thrombotic events in patients with unprovoked venous thromboembolism and in those whose thrombosis occurred in association with a known risk factor, such as surgery. In Section II, Dr. William Geerts reviews the pharmacology of new parenteral and oral factor Xa inhibitors and describes the results of the Phase II and III clinical trials with these agents. He then provides perspective on the potential advantages and drawbacks of these drugs for the prevention and treatment of venous thromboembolism. In Section III, Dr. John Heit focuses on direct thrombin inhibitors. He discusses their mechanism of action and compares and contrasts their pharmacological profiles prior to describing the results of Phase II and III clinical trials. Dr. Heit then provides perspective on the potential advantages and limitations of these drugs relative to existing anticoagulants.


2017 ◽  
Vol 43 (06) ◽  
pp. 614-620 ◽  
Author(s):  
Vera Gessi ◽  
Rossella Marcucci ◽  
Monica Gianni ◽  
Anna Grandi ◽  
Massimo Franchini ◽  
...  

AbstractElevated plasma levels of lipoprotein(a) (Lp(a)) are associated with increased cardiovascular risk in several clinical studies. However, there is a lack of data supporting a positive association between elevated Lp(a) levels and venous thromboembolism (VTE). Thus, we conducted a systematic review of the literature to better clarify its role as a risk factor for VTE. Medline and the Embase (up to May 2015) electronic databases were used to identify potentially eligible studies. Studies measuring Lp(a) values in adult patients with deep vein thrombosis and/or pulmonary embolism and in a population of patients without a VTE were selected. Studies on patients with major venous thromboembolic events occurring at other unusual site, case reports, and case series were excluded. The odds ratios (ORs) of the association between high values of Lp(a) and VTE and the weighted mean difference (WMD) in Lp(a) levels in cases and in controls were calculated using a random-effect model. Results were presented with 95% confidence interval (CI). Fourteen studies for a total of more than 14,000 patients were finally included in our analysis. Lp(a) was slightly but significantly associated with an increased risk of VTE (OR: 1.56, 95% CI: 1.36, 1.79; 10 studies, 13,541 patients). VTE patients had significantly higher Lp(a) values compared with controls (WMD: 14.46 mg/L, 95% CI: 12.14, 16.78; 4 studies, 470 patients). Lp(a) appeared to be significantly associated with increased risk of VTE. However, Lp(a) levels were only slightly increased in VTE patients compared with controls.


2010 ◽  
Vol 103 (06) ◽  
pp. 1152-1160 ◽  
Author(s):  
Cristina Legnani ◽  
Alberto Tosetto ◽  
Vittorio Pengo ◽  
Angelo Ghirarduzzi ◽  
Sophie Testa ◽  
...  

SummaryThe PROLONG randomised clinical trial showed that an abnormal D-dimer at one month after vitamin K antagonist (VKA) suspension for a first episode of unprovoked venous thromboembolism (VTE) is associated with a higher risk of recurrence. However, other patient characteristics, such as comorbidities, in combination with D-dimer could also influence the recurrence risk. It was the objective of this study to assess the predictive value of comorbidities and D-dimer in combination for recurrence after withdrawal of VKA in patients enrolled in the PROLONG study. On the day of VKA suspension, the presence of known (coronary, peripheral,cerebral) vascular disease, chronic inflammatory bowel disease, chronic obstructive pulmonary disease, autoimmune disease, diabetes, arterial hypertension, obesity and dyslipidaemias was registered. D-dimer was measured at 30 ± 10 days afterwards. The primary outcome was recurrent objectively documented VTE. Mean follow-up was 2.55 years. An abnormal D-dimer was observed in 44% (135/309) of patients with comorbidities and in 29% (87/299) of patients without (p=0.0003). An on-treatment analysis was conducted in 483 patients in whom VKAs were not resumed. In patients with a normal D-dimer, recurrences were observed in 14.3% (24/168) of patients with comorbidities and 10.8% (22/203) of subjects without (p=ns). In patients with an abnormal D-dimer, recurrences were observed in 24.6% (16/65) patients with comorbidities and 21.3% (10/47) of patients without (p=ns). Although abnormal D-dimer levels were significantly more frequent in patients with comorbidities, D-dimer was an independent risk factor for recurrence and the presence of comorbidities did not increase the risk of recurrence associated with an abnormal post-anticoagulation D-dimer.ClinicalTrials.gov number: NCT00264277


1999 ◽  
Vol 82 (S 01) ◽  
pp. 124-126 ◽  
Author(s):  
H. H. Watzke

SummaryA number of studies have been published in the last years which shed light on the optimal intensity and the optimal duration of oral anticoagulation in patients with venous thrombosis.Based on these studies it is now generally recommended to treat patients with venous thromboembolism at an INR ranging from 2.0 to 3.0. The optimal duration of anticoagulation mainly depends on the nature of the thrombotic event. In patients with a temporary prothrombotic risk factor such as surgery, immobilization or trauma a relatively short duration of oral anticoagulation (3-6 months) is generally recommended. Patients with idiopathic venous thromboembolism require a considerably longer duration of anticoagulation (6 months at least).


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