Whether to continue oral anticoagulant therapy beyond 6 months after an "unprovoked" venous thromboembolism is controversial. We sought to determine clinical predictors to identify patients who are ...at low risk of recurrent venous thromboembolism who could safely discontinue oral anticoagulants.
In a multicentre prospective cohort study, 646 participants with a first, unprovoked major venous thromboembolism were enrolled over a 4-year period. Of these, 600 participants completed a mean 18-month follow-up in September 2006. We collected data for 69 potential predictors of recurrent venous thromboembolism while patients were taking oral anticoagulation therapy (5-7 months after initiation). During follow-up after discontinuing oral anticoagulation therapy, all episodes of suspected recurrent venous thromboembolism were independently adjudicated. We performed a multivariable analysis of predictor variables (p < 0.10) with high interobserver reliability to derive a clinical decision rule.
We identified 91 confirmed episodes of recurrent venous thromboembolism during follow-up after discontinuing oral anticoagulation therapy (annual risk 9.3%, 95% CI 7.7%-11.3%). Men had a 13.7% (95% CI 10.8%-17.0%) annual risk. There was no combination of clinical predictors that satisfied our criteria for identifying a low-risk subgroup of men. Fifty-two percent of women had 0 or 1 of the following characteristics: hyperpigmentation, edema or redness of either leg; D-dimer > or = 250 microg/L while taking warfarin; body mass index > or = 30 kg/m(2); or age > or = 65 years. These women had an annual risk of 1.6% (95% CI 0.3%-4.6%). Women who had 2 or more of these findings had an annual risk of 14.1% (95% CI 10.9%-17.3%).
Women with 0 or 1 risk factor may safely discontinue oral anticoagulant therapy after 6 months of therapy following a first unprovoked venous thromboembolism. This criterion does not apply to men.
The optimal duration of oral anticoagulant therapy after a first, unprovoked venous thromboembolism is controversial due to tightly balanced risks and benefits of indefinite anticoagulation. Risk ...stratification tools may assist in decision making.
We sought to determine the relationship between residual pulmonary embolism assessed by baseline ventilation-perfusion scan after completion of 5–7months of oral anticoagulant therapy and the risk of recurrent venous thromboembolism in patients with the first episode of unprovoked pulmonary embolism.
We conducted a multicentre prospective cohort study of participants with a first, unprovoked venous thromboembolism enrolled after the completion of 5–7months of oral anticoagulation therapy. The participants completed a mean 18-month follow-up. Participants with pulmonary embolism had baseline ventilation-perfusion scan before discontinuation of oral anticoagulant therapy and the percentage of vascular obstruction on baseline ventilation-perfusion scan was determined. During follow-up after discontinuation of oral anticoagulant therapy, all episodes of suspected recurrent venous thromboembolism were independently adjudicated with reference to baseline imaging.
During follow-up, 24 of 239 (10.0%) participants with an index event of isolated pulmonary embolism or pulmonary embolism associated with deep vein thrombosis and central assessment of percentage of vascular obstruction on baseline ventilation-perfusion scan had confirmed recurrent venous thromboembolism. As compared to participants with no residual pulmonary embolism on baseline ventilation-perfusion scan, the hazard ratio for recurrent venous thromboembolism was 2.0 (95% CI 0.5–7.3) for participants with percentage of vascular obstruction of 0.1%–4.9%, 2.1 (95% CI 0.5–7.8) for participants with percentage vascular obstruction of 5.0%–9.9% and 5.3 (95% CI 1.8–15.4) for participants with percentage vascular obstruction greater than or equal to 10%.
Residual pulmonary embolism assessed by pulmonary vascular obstruction on baseline ventilation-perfusion performed after 5–7months of oral anticoagulant therapy for the first episode of unprovoked pulmonary embolism was associated with a statistically significant higher risk of subsequent recurrent venous thromboembolism. Percentage of pulmonary vascular obstruction assessment by ventilation-perfusion scans maybe a useful tool to help guide the duration of oral anticoagulant therapy after a first unprovoked pulmonary embolism.
Registered at www.clinicaltrials.gov identifier: NCT00261014.
•Optimal duration of OAT after a first, unprovoked VTE is controversial.•Better prediction of the risk of recurrent VTE after OAT discontinuation is necessary.•Residual PE can be assessed by percentage of vascular obstruction (PVO).•PVO after 5–7months OAT was associated with a higher risk of recurrent VTE.•PVO assessment by V/Q scans maybe a useful tool to help guide the duration of OAT.
This trial showed that the addition of abdominopelvic CT to routine measures in patients with unprovoked venous thrombosis did not detect additional occult cancers. The incidence of cancer in first ...unprovoked venous thrombosis was 4%, not 10% as had been previously reported.
Venous thromboembolism, which comprises deep-vein thrombosis and pulmonary embolism, is the third most common cardiovascular disorder.
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It is classified as provoked when it is associated with a transient risk factor (e.g., trauma, surgery, prolonged immobility, or pregnancy or the puerperium) and as unprovoked when it is associated with neither a strong transient risk factor nor overt cancer.
Unprovoked venous thromboembolism may be the earliest sign of cancer
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; up to 10% of patients with unprovoked venous thromboembolism receive a diagnosis of cancer in the year after their diagnosis of venous thromboembolism.
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More than 60% of occult cancers are . . .
Summary Background Post-thrombotic syndrome (PTS) is a common and burdensome complication of deep venous thrombosis (DVT). Previous trials suggesting benefit of elastic compression stockings (ECS) to ...prevent PTS were small, single-centre studies without placebo control. We aimed to assess the efficacy of ECS, compared with placebo stockings, for the prevention of PTS. Methods We did a multicentre randomised placebo-controlled trial of active versus placebo ECS used for 2 years to prevent PTS after a first proximal DVT in centres in Canada and the USA. Patients were randomly assigned to study groups with a web-based randomisation system. Patients presenting with a first symptomatic, proximal DVT were potentially eligible to participate. They were excluded if the use of compression stockings was contraindicated, they had an expected lifespan of less than 6 months, geographical inaccessibility precluded return for follow-up visits, they were unable to apply stockings, or they received thrombolytic therapy for the initial treatment of acute DVT. The primary outcome was PTS diagnosed at 6 months or later using Ginsberg's criteria (leg pain and swelling of ≥1 month duration). We used a modified intention to treat Cox regression analysis, supplemented by a prespecified per-protocol analysis of patients who reported frequent use of their allocated treatment. This study is registered with ClinicalTrials.gov , number NCT00143598 , and Current Controlled Trials, number ISRCTN71334751. Findings From 2004 to 2010, 410 patients were randomly assigned to receive active ECS and 396 placebo ECS. The cumulative incidence of PTS was 14·2% in active ECS versus 12·7% in placebo ECS (hazard ratio adjusted for centre 1·13, 95% CI 0·73–1·76; p=0·58). Results were similar in a prespecified per-protocol analysis of patients who reported frequent use of stockings. Interpretation ECS did not prevent PTS after a first proximal DVT, hence our findings do not support routine wearing of ECS after DVT. Funding Canadian Institutes of Health Research.
Thrombophilia predisposes to venous thromboembolism (VTE) because of acquired or hereditary factors. Among them, it has been suggested that gene mutations of the factor V Leiden (FVL) or prothrombin ...G20210A mutation (PGM) might reduce the risk of bleeding, but little data exist for patients treated using anticoagulants.
To assess whether thrombophilia is protective against bleeding.
This multicentre, multinational, prospective cohort study evaluated adults receiving long-term anticoagulants after a VTE event. We analyzed the incidence of major bleeding as the primary outcome, according to the genotype for FVL and PGM (wild-type and heterozygous/homozygous carriers).
Of 2260 patients with genotype testing, during a median follow-up of 3 years, 106 patients experienced a major bleeding event (17 intracranial and 7 fatal). Among 439 carriers of FVL, 19 experienced major bleeding and there were no differences between any mutation vs wild-type (hazard ratio HR, 0.89 0.53-1.49; p = .66). The comparison of major bleeding events between the 158 patients with any-PGM mutation (heterozygous or homozygous) vs wild-type also showed a nonstatistically significant difference with HR of 0.53 (0.19-1.43), p = .21. However, multivariate analysis demonstrated that major bleeds or clinically relevant nonmajor bleeding were statistically less likely for patients with either FVL and/or PGM compared with patients with both wild-type factor V and prothrombin genes (HR, 0.73; 95% CI = 0.55-0.97; p = .03).
This study demonstrates that thrombophilia, defined as the presence of either FVL or the prothrombin G20210A mutation, is related with a lower rate of major/clinically relevant nonmajor bleeding while on anticoagulants in the extended treatment for VTE.
•Thrombophilia is a status predisposing to venous thromboembolism, but it is unclear whether it is a protective factor against bleeding in patients on long treatment with anticoagulants for venous thrombosis.•We conducted a multicentre, multinational, prospective cohort study to evaluate the association between bleeding and factor V Leiden and prothrombin G20210A mutation.•During a median follow-up of 3 years, there was a nonstatistically significant difference between factor V Leiden or prothrombin G20210A mutation compared with wild-type.•Multivariate analysis has shown fewer bleeding events (major or clinically relevant nonmajor bleeding) for patients with factor V Leiden and/or prothrombin G20210A mutation vs both wild-type factor V and prothrombin genes.
Introduction
The risk of recurrent venous thromboembolism (VTE) after combined oral contraceptive (COC) use is variably reported. We assessed the long‐term risk of recurrent VTE in women on COC at ...the time of a first VTE, in comparison to women without COC use. Our secondary aim assessed the impact of COC use on the recurrent VTE risk in high‐risk and low‐risk hyperpigmentation, edema, or redness in either leg; D‐dimer level ≥250 μg/L; obesity with body mass index ≥30; or older age, ≥65 years (HERDOO2) subgroups.
Methods
The REVERSE cohort study derived the HERDOO2 clinical decision rule to predict recurrent VTE in patients who discontinued anticoagulation after 5–7 months for a first unprovoked VTE. Incidence rates of recurrent VTE among women with and without COC exposure were calculated as the number of recurrent VTE over the number of person‐years of follow‐up, and Cox proportional hazards model was used to compare risks between groups.
Results
The risk of recurrent VTE among COC users was 1.1% (95% confidence interval CI 0.3–2.9) per patient‐year as compared with 3.2% per patient‐year (95% CI 2.4–4.3) among nonusers (hazard ratio 0.37; 95% CI 0.1–1.0). Women who were COC users and high risk by HERDOO2 score had a recurrence rate of 3.5% (95% CI 0.4–12.5) compared with 6.1% (95% CI 4.3–8.5) among women who were non‐COC users and at high risk by HERDOO2 score (HR 0.6, 95% CI 0.1–2.5).
Conclusions
Women who were COC users at the time of an otherwise unprovoked VTE event had a lower VTE recurrence rate during long‐term follow‐up, compared with nonusers. The use of HERDOO2 rule may help identify higher risk women with COC use.
While several risk stratification tools have been developed to predict the risk of recurrence in patients with an unprovoked venous thromboembolism (VTE), only 1 in 4 patients are categorized as ...low-risk. Rather than a one-time measure, serial D-dimer assessment holds promise to enhance the prediction of VTE recurrence after oral anticoagulant (OAC) cessation.
Using the REVERSE cohort, we compared VTE recurrence among patients with normal D-dimer levels (<490 ng/mL among males under age 70, <500 ng/mL in others) at OAC cessation and 1-month follow-up, to those with an elevated D-dimer level at either timepoint. We also evaluated VTE recurrence based on absolute increase in D-dimer levels between the two timepoints (e.g., ∆D-dimer) according to quartiles.
Among 214 patients with serial D-dimer levels measured at OAC cessation and 1-month follow-up, an elevated D-dimer level at either timepoint was associated with a numerically higher risk of recurrent VTE than patients with normal D-dimer levels at both timepoints (6.9 % vs. 4.2 % per year, hazard ratio 1.6; 95 % CI 0.9–2.7). Among women with <2 HERDOO2 criteria, a normal D-dimer level at both timepoints predicted a very low risk of recurrent VTE during follow-up (0.8 % per year, 95 % CI 0.1–2.8). Irrespective of baseline value, recurrent VTE risk was only 3 % per year (95 % CI 1.4–5.6) among patients in the lowest ∆D-dimer quartile.
Serial normal D-dimer levels have the potential to identify patients at a low risk of recurrent VTE. In addition, ∆D-dimer, irrespective of its elevation above cutoff threshold, may predict recurrent VTE.
•>50 % of unprovoked VTE will not recur over the long-term despite stopping treatment.•Current strategies only identify 1 in 4 individuals at low risk of VTE recurrence.•We analyzed a cohort to determine if serial D-dimers provided better prediction.•Normal D-dimer at baseline and 1-month post-treatment predicted low VTE recurrence.•Lowest ΔD-dimer quartile from baseline to 1 month had additional prognostic value.
To evaluate a diagnostic strategy for pulmonary embolism that combined clinical assessment, plasma D-dimer measurement, lower limb venous ultrasonography, and helical computed tomography (CT).
A ...cohort of 965 consecutive patients presenting to the emergency departments of three general and teaching hospitals with clinically suspected pulmonary embolism underwent sequential noninvasive testing. Clinical probability was assessed by a prediction rule combined with implicit judgment. All patients were followed for 3 months.
A normal D-dimer level (<500 μg/L by a rapid enzyme-linked immunosorbent assay) ruled out venous thromboembolism in 280 patients (29%), and finding a deep vein thrombosis by ultrasonography established the diagnosis in 92 patients (9.5%). Helical CT was required in only 593 patients (61%) and showed pulmonary embolism in 124 patients (12.8%). Pulmonary embolism was considered ruled out in the 450 patients (46.6%) with a negative ultrasound and CT scan and a low-to-intermediate clinical probability. The 8 patients with a negative ultrasound and CT scan despite a high clinical probability proceeded to pulmonary angiography (positive: 2; negative: 6). Helical CT was inconclusive in 11 patients (pulmonary embolism: 4; no pulmonary embolism: 7). The overall prevalence of pulmonary embolism was 23%. Patients classified as not having pulmonary embolism were not anticoagulated during follow-up and had a 3-month thromboembolic risk of 1.0% (95% confidence interval: 0.5% to 2.1%).
A noninvasive diagnostic strategy combining clinical assessment, D-dimer measurement, ultrasonography, and helical CT yielded a diagnosis in 99% of outpatients suspected of pulmonary embolism, and appeared to be safe, provided that CT was combined with ultrasonography to rule out the disease.
The 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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