The Risk of Recurrent Venous Thromboembolism in Patients with and without Factor V Leiden

Eichinger, Sabine; Pabinger, Ingrid; Stümpflen, Andreas; Hirschl, Mirko; Bialonczyk, Christine; Schneider, Barbara; Mannhalter, Christine; Minar, Erich; Lechner, Klaus; Kyrle, Paul A.

doi:10.1055/s-0038-1656023

Cited by 208 publications

(131 citation statements)

References 37 publications

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“…In other hereditary thrombophilias, the annual incidence of recurrent venous thromboembolism seems to decline after the first years. 29 Surprisingly, Eichinger et al 30 found no increased risk of recurrent venous thromboembolic events in patients with the FVL mutation during the first 2 years after discontinuation of oral anticoagulants. In a recent study of the effect of prophylactic oral anticoagulation after a second peripheral venous thromboembolism, indefinite continuation of the therapy was superior to a 6-month treatment with respect to recurrence (2.6% versus 20.7%).…”

Section: Discussionmentioning

confidence: 99%

Factor V Leiden Mutation Is a Risk Factor for Cerebral Venous Thrombosis

Lüdemann

Nabavi

Junker

et al. 1998

Stroke

112

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Background and Purpose-Different coagulation disorders have been associated with cerebral venous thrombosis (CVT).Until now, fewer than 50 patients have been reported with CVT and the factor V Leiden (FVL) mutation. Although the prevalence of FVL-positive patients with CVT ranged from 10% to 25%, it was as low as 0.5% to 3% in the control groups. Most other studies had not systematically searched for concomitant risk factors or previous thromboembolic events. To better define the relevance of the FVL mutation in conjunction with additional risk factors in CVT, we conducted the present case-control study. Methods-Fifty-five patients with CVT were compared with 272 healthy controls. A standardized interview regarding established risk factors for venous thrombosis and the patients' and their families' histories for thromboembolic events was performed. The presence of the FVL mutation was determined by polymerase chain reaction on DNA obtained from peripheral blood leukocytes. Results-Of 55 patients, 8 (14.5%) were heterozygous for the FVL mutation compared with 17 of 272 controls (6.25%).The relative risk for the presence of FVL was 2.55 (95% confidence interval, 1.04 to 6.26; Pϭ0.04). Additional risk factors for CVT were frequently found in both the presence and absence of FVL. Recurrence of venous thromboembolic events was more frequent in patients with the FVL mutation (5 of 8 patients, 62.5%) than in those without this anomaly (8 of 47 patients, 17%; PϽ0.005). Conclusions-Our

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Section: Discussionmentioning

confidence: 99%

Factor V Leiden Mutation Is a Risk Factor for Cerebral Venous Thrombosis

Lüdemann

Nabavi

Junker

et al. 1998

Stroke

112

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“…Such a conclusion has been drawn in some studies 16,17 but was not confirmed by other authors. 18,19 In a recent prospective study 20 in subjects with a previous first VTE event, we showed that normal D-dimer levels obtained after OAT withdrawal had a very high negative predictive value for VTE recurrence. Conversely, increased D-dimer levels were associated with a significantly higher hazard ratio for recurrence.…”

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confidence: 89%

Predictive Value of D-Dimer Test for Recurrent Venous Thromboembolism After Anticoagulation Withdrawal in Subjects With a Previous Idiopathic Event and in Carriers of Congenital Thrombophilia

et al. 2003

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Background-We have shown that normal D-dimer levels obtained after the discontinuation of oral anticoagulant treatment (OAT) has a high negative predictive value for recurrent venous thromboembolism (VTE). The aim of the present study was to assess the predictive value of D-dimer for recurrent VTE in subjects with a previous unprovoked event who are either carriers of inherited thrombophilia or not. Methods and Results-We prospectively evaluated 599 patients (301 males) with a previous VTE episode. They were repeatedly examined for D-dimer levels after OAT withdrawal and were screened for inherited thrombophilic alterations. Alterations were detected in 130 patients (21.7%), factor V Leiden (70 patients; 2 of whom were homozygotes) and prothrombin mutation (38 patients) were the most prevalent ones. Recurrent events were recorded in 58 subjects (9.7%) during a follow-up of 870.7 patient-years. Altered D-dimer levels at 1 month after OAT withdrawal were associated with a higher rate of subsequent recurrence in all subjects investigated, especially in those with an unprovoked qualifying VTE event (hazard ratio, 2.43; 95% confidence interval, 1.18 to 4.61) and in those with thrombophilia (hazard ratio, 8.34; 95% confidence interval, 2.72 to 17.43). The higher relative risk for recurrence of altered D-dimer was confirmed by multivariate analysis after adjustment for other risk factors. The negative predictive value of D-dimer was 92.9% and 95.8% in subjects with an unprovoked qualifying event or with thrombophilia, respectively. Conclusions-D-dimer levels measured 1 month after OAT withdrawal have a high negative predictive value for recurrence in subjects with unprovoked VTE who are either carriers or not carriers of congenital thrombophilia.

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“…The role of thrombophilic abnormalities, especially those that are highly prevalent in western countries (i.e., factor V Leiden and prothrombin G20210A mutation), is controversial. [5][6][7][8][9][10][11][12][13][14] Although recent data suggest that clinical presentation with primary PE 15 and male sex [16][17][18] increase the risk of recurrent VTE, these findings still await confirmation. Finally, whether the duration of anticoagulation following the initial thrombotic episode has any influence on the subsequent rate of recurrent VTE is uncertain.…”

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confidence: 99%

The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients

Prandoni

Noventa²,

Ghirarduzzi³

et al. 2007

Haematologica

691

510

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While it has long been recognized that patients with acute unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) have a higher risk of recurrent venous thromboembolism (VTE) than that of patients with secondary thrombosis, whether other clinical parameters can help predict the development of recurrent events is controversial. The aim of this investigation was to assess the rate of recurrent VTE after withdrawal of vitamin K antagonists, and to identify clinical parameters associated with a higher likelihood of recurrence. Design and MethodsWe followed, up to a maximum of 10 years, 1626 consecutive patients who had discontinued anticoagulation after a first episode of clinically symptomatic proximal DVT and/or PE. All patients with clinically suspected recurrent VTE underwent objective tests to confirm or rule out the clinical suspicion. ResultsAfter a median follow-up of 50 months, 373 patients (22.9%) had had recurrent episodes of VTE. The cumulative incidence of recurrent VTE was 11.0% (95% CI, 9.5-12.5) after 1 year, 19.6% (17.5-21.7) after 3 years, 29.1% (26.3-31.9) after 5 years, and 39.9% (35.4-44.4) after 10 years. The adjusted hazard ratio for recurrent VTE was 2.30 (95% CI, 1.82-2.90) in patients whose first VTE was unprovoked, 2.02 (1.52-2.69) in those with thrombophilia, 1.44 (1.03-2.03) in those presenting with primary DVT, 1.39 (1.08-1.80) for patients who received a shorter (up to 6 months) duration of anticoagulation, and 1.14 (1.06-1.12) for every 10-year increase of age. When the analysis was confined to patients with unprovoked VTE the results did not change. Interpretation and ConclusionsBesides unprovoked presentation, other factors independently associated with a statistically significant increased risk of recurrent VTE are thrombophilia, clinical presentation with primary DVT, shorter duration of anticoagulation, and increasing age. 1-6 While it is generally accepted that patients with thromboembolic events of unknown origin have a more than two-fold higher rate of recurrent VTE in comparison to patients whose thrombosis is associated with acquired, transient risk factors, 1-6 whether other of the patients' baseline features can help to identify those subjects who might benefit from prolonged anticoagulation is unclear. For example, it is virtually unknown whether aging, an important risk factor for VTE, 4 is also associated with an increased risk of recurrence. The role of thrombophilic abnormalities, especially those that are highly prevalent in western countries (i.e., factor V Leiden and prothrombin G20210A mutation), is controversial.5-14 Although recent data suggest that clinical presentation with primary PE 15 and male sex 16-18 increase the risk of recurrent VTE, these findings still await confirmation. Finally, whether the duration of anticoagulation following the initial thrombotic episode has any influence on the subsequent rate of recurrent VTE is uncertain. 2,19-22Here we report on the prospective long-term followup of a large series of patients with proximal DVT and...

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The Risk of Recurrent Venous Thromboembolism in Patients with and without Factor V Leiden

Cited by 208 publications

References 37 publications

Factor V Leiden Mutation Is a Risk Factor for Cerebral Venous Thrombosis

Factor V Leiden Mutation Is a Risk Factor for Cerebral Venous Thrombosis

Predictive Value of D-Dimer Test for Recurrent Venous Thromboembolism After Anticoagulation Withdrawal in Subjects With a Previous Idiopathic Event and in Carriers of Congenital Thrombophilia

The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients

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