The primary goal of diagnostic testing for venous thromboembolism (VTE) is to identify all patients who could benefit from anticoagulant therapy. Test results that identify patients as having a ≤2% ...risk of VTE in the next 3 months are judged to exclude deep vein thrombosis (DVT) or pulmonary embolism (PE). Clinical evaluation, with assessment of: (1) clinical pretest probability (CPTP) for VTE; (2) likelihood of important alternative diagnoses; and (3) the probable yield of D-dimer and various imaging tests, guide which tests should be performed. The combination of nonhigh CPTP and negative D-dimer testing excludes DVT or PE in one-third to a half of outpatients. Venous ultrasound of the proximal veins, with or without examination of the distal veins, is the primary imaging test for leg and upper-extremity DVT. If a previous test is not available for comparison, the positive predictive value of ultrasound is low in patients with previous DVT. Computed tomography pulmonary angiography (CTPA) is the primary imaging test for PE and often yields an alternative diagnosis when there is no PE. Ventilation-perfusion scanning is associated with less radiation exposure than CTPA and is preferred in younger patients, particularly during pregnancy. If DVT or PE cannot be "ruled-in" or "ruled-out" by initial diagnostic testing, patients can usually be managed safely by: (1) withholding anticoagulant therapy; and (2) doing serial ultrasound examinations to detect new or extending DVT.
Most deep vein thromboses (DVTs) start in the calf, and most probably resolve spontaneously. Thrombi that remain confined to the calf rarely cause leg symptoms or symptomatic pulmonary embolism (PE). ...The probability that calf DVT will extend to involve the proximal veins and subsequently cause PE increases with the severity of the initiating prothrombotic stimulus. Although acute venous thromboembolism (VTE) usually presents with either leg or pulmonary symptoms, most patients have thrombosis at both sites at the time of diagnosis. Proximal DVTs resolve slowly during treatment with anticoagulants, and thrombi remain detectable in half of the patients after a year. Resolution of DVT is less likely in patients with a large initial thrombus or cancer. About 10% of patients with symptomatic DVTs develop severe post-thrombotic syndrome within 5 years, and recurrent ipsilateral DVT increases this risk. About 10% of PEs are rapidly fatal, and an additional 5% cause death later, despite diagnosis and treatment. About 50% of diagnosed PEs are associated with right ventricular dysfunction, which is associated with a approximately 5-fold greater in-hospital mortality. There is approximately 50% resolution of PE after 1 month of treatment, and perfusion eventually returns to normal in two thirds of patients. About 5% of treated patients with PE develop pulmonary hypertension as a result of poor resolution. After a course of treatment, the risk of recurrent thrombosis is higher (ie, approximately 10% per patient-year) in patients without reversible risk factors, in those with cancer, and in those with prothrombotic biochemical abnormalities such as antiphospholipid antibodies and homozygous factor V Leiden.
Patients with venous thromboembolism who had received initial anticoagulant therapy were studied in two trials of dabigatran. Dabigatran was effective in preventing recurrent venous thromboembolism ...and carried a lower risk of bleeding than warfarin but a higher risk than placebo.
Anticoagulant treatment with vitamin K antagonists is recommended for patients with venous thromboembolism.
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Most patients receive at least 3 months of treatment. Long-term treatment is recommended if there are risk factors for recurrence, such as multiple thrombotic episodes.
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In the absence of clear contraindications to anticoagulant therapy, the risk of major bleeding is approximately 1% per year with extended vitamin K antagonist therapy after venous thromboembolism.
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The risk of major bleeding, together with the need for frequent laboratory monitoring and dose adjustments, makes long-term treatment problematic.
Dabigatran, a direct thrombin inhibitor, does not require frequent monitoring and dose adjustments. At . . .
It takes about 3 months to complete “active treatment” of venous thromboembolism (VTE), with further treatment serving to prevent new episodes of thrombosis (“pure secondary prevention”). ...Consequently, VTE should generally be treated for either 3 months or indefinitely (exceptions will be described in the text). The decision to stop anticoagulants at 3 months or to treat indefinitely is dominated by the long-term risk of recurrence, and secondarily influenced by the risk of bleeding and by patient preference. VTE provoked by a reversible risk factor, or a first unprovoked isolated distal (calf) deep vein thrombosis (DVT), has a low risk of recurrence and is usually treated for 3 months. VTE associated with active cancer, or a second unprovoked VTE, has a high risk of recurrence and is usually treated indefinitely. The decision to stop anticoagulants at 3 months or to treat indefinitely is more finely balanced after a first unprovoked proximal DVT or pulmonary embolism (PE). Indefinite anticoagulation is often chosen if there is a low risk of bleeding, whereas anticoagulation is usually stopped at 3 months if there is a high risk of bleeding. The decision to continue anticoagulation indefinitely after a first unprovoked proximal DVT or PE is strengthened if the patient is male, the index event was PE rather than DVT, and/or d-dimer testing is positive 1 month after stopping anticoagulant therapy.
This article about hemorrhagic complications of anticoagulant and thrombolytic treatment is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based ...Clinical Practice Guidelines (8th Edition). Bleeding is the major complication of anticoagulant and fibrinolytic therapy. The criteria for defining the severity of bleeding vary considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist (VKA)-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that VKA therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0-3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0.
The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism is < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 70 years). Low-molecular-weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute venous thromboembolism. Higher doses of UFH and LMWH are associated with important increases in major bleeding in ischemic stroke. In ST-segment elevation myocardial infarction, addition of LMWH, hirudin, or its derivatives to thrombolytic therapy is associated with a small increase in the risk of major bleeding, whereas treatment with fondaparinux or UFH is associated with a lower risk of bleeding.
Thrombolytic therapy increases the risk of major bleeding 1.5-fold to threefold in patients with acute venous thromboembolism, ischemic stroke, or ST-elevation myocardial infarction.
Among patients with a low clinical pretest probability of pulmonary embolism and a
d
-dimer level of less than 1000 ng per milliliter (twice the usual threshold used to rule out the disorder), the ...need for diagnostic imaging was reduced from 51.9% to 34.3% of patients, without increasing the risk of missing the diagnosis of pulmonary embolism.
Patients with proximal deep-vein thrombosis were assigned to undergo anticoagulation either alone or combined with pharmacomechanical thrombolysis. After 6 to 24 months, there was no significant ...between-group difference in the incidence of the post-thrombotic syndrome.
In this comparative-effectiveness trial, the oral direct thrombin inhibitor dabigatran was shown to be as effective as warfarin in the prevention of recurrent venous thromboembolism. Bleeding ...complications were similar. Dabigatran therapy offers the advantage that monitoring of anticoagulation is not necessary.
In this comparative-effectiveness trial, the oral direct thrombin inhibitor dabigatran was shown to be as effective as warfarin in the prevention of recurrent venous thromboembolism. Dabigatran therapy offers the advantage that monitoring of anticoagulation is not necessary.
Venous thromboembolism affects 1 to 2 adults per 1000 annually and is the third most common cause of vascular death after myocardial infarction and stroke.
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,
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The current standard treatment is rapidly acting parenteral anticoagulation for 5 to 7 days followed by at least 3 months of treatment with a vitamin K antagonist.
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Treatment with a vitamin K antagonist requires frequent monitoring of the international normalized ratio (INR), and multiple interactions of vitamin K antagonists with foods and other drugs have been reported.
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Dabigatran etexilate (hereafter termed dabigatran) is an orally available, potent, direct inhibitor of thrombin. It is rapidly . . .
This chapter about treatment for venous thromboembolic disease is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations ...are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading, see “Grades of Recommendation” chapter). Among the key recommendations in this chapter are the following: for patients with objectively confirmed deep vein thrombosis (DVT) or pulmonary embolism (PE), we recommend anticoagulant therapy with subcutaneous (SC) low-molecular-weight heparin (LMWH), monitored IV, or SC unfractionated heparin (UFH), unmonitored weight-based SC UFH, or SC fondaparinux (all Grade 1A). For patients with a high clinical suspicion of DVT or PE, we recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C). For patients with confirmed PE, we recommend early evaluation of the risks to benefits of thrombolytic therapy (Grade 1C); for those with hemodynamic compromise, we recommend short-course thrombolytic therapy (Grade 1B); and for those with nonmassive PE, we recommend against the use of thrombolytic therapy (Grade 1B). In acute DVT or PE, we recommend initial treatment with LMWH, UFH or fondaparinux for at least 5 days rather than a shorter period (Grade 1C); and initiation of vitamin K antagonists (VKAs) together with LMWH, UFH, or fondaparinux on the first treatment day, and discontinuation of these heparin preparations when the international normalized ratio (INR) is ≥ 2.0 for at least 24 h (Grade 1A). For patients with DVT or PE secondary to a transient (reversible) risk factor, we recommend treatment with a VKA for 3 months over treatment for shorter periods (Grade 1A). For patients with unprovoked DVT or PE, we recommend treatment with a VKA for at least 3 months (Grade 1A), and that all patients are then evaluated for the risks to benefits of indefinite therapy (Grade 1C). We recommend indefinite anticoagulant therapy for patients with a first unprovoked proximal DVT or PE and a low risk of bleeding when this is consistent with the patient's preference (Grade 1A), and for most patients with a second unprovoked DVT (Grade 1A). We recommend that the dose of VKA be adjusted to maintain a target INR of 2.5 (INR range, 2.0 to 3.0) for all treatment durations (Grade 1A). We recommend at least 3 months of treatment with LMWH for patients with VTE and cancer (Grade 1A), followed by treatment with LMWH or VKA as long as the cancer is active (Grade 1C). For prevention of postthrombotic syndrome (PTS) after proximal DVT, we recommend use of an elastic compression stocking (Grade 1A). For DVT of the upper extremity, we recommend similar treatment as for DVT of the leg (Grade 1C). Selected patients with lower-extremity (Grade 2B) and upper-extremity (Grade 2C). DVT may be considered for thrombus removal, generally using catheter-based thrombolytic techniques. For extensive superficial vein thrombosis, we recommend treatment with prophylactic or intermediate doses of LMWH or intermediate doses of UFH for 4 weeks (Grade 1B).
AbstractObjectivesTo determine the rate of a first recurrent venous thromboembolism (VTE) event after discontinuation of anticoagulant treatment in patients with a first episode of unprovoked VTE, ...and the cumulative incidence for recurrent VTE up to 10 years.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, and the Cochrane Central Register of Controlled Trials (from inception to 15 March 2019).Study selectionRandomised controlled trials and prospective cohort studies reporting symptomatic recurrent VTE after discontinuation of anticoagulant treatment in patients with a first unprovoked VTE event who had completed at least three months of treatment.Data extraction and synthesisTwo investigators independently screened studies, extracted data, and appraised risk of bias. Data clarifications were sought from authors of eligible studies. Recurrent VTE events and person years of follow-up after discontinuation of anticoagulant treatment were used to calculate rates for individual studies, and data were pooled using random effects meta-analysis. Sex and site of initial VTE were investigated as potential sources of between study heterogeneity.Results18 studies involving 7515 patients were included in the analysis. The pooled rate of recurrent VTE per 100 person years after discontinuation of anticoagulant treatment was 10.3 events (95% confidence interval 8.6 to 12.1) in the first year, 6.3 (5.1 to 7.7) in the second year, 3.8 events/year (95% confidence interval 3.2 to 4.5) in years 3-5, and 3.1 events/year (1.7 to 4.9) in years 6-10. The cumulative incidence for recurrent VTE was 16% (95% confidence interval 13% to 19%) at 2 years, 25% (21% to 29%) at 5 years, and 36% (28% to 45%) at 10 years. The pooled rate of recurrent VTE per 100 person years in the first year was 11.9 events (9.6 to 14.4) for men and 8.9 events (6.8 to 11.3) for women, with a cumulative incidence for recurrent VTE of 41% (28% to 56%) and 29% (20% to 38%), respectively, at 10 years. Compared to patients with isolated pulmonary embolism, the rate of recurrent VTE was higher in patients with proximal deep vein thrombosis (rate ratio 1.4, 95% confidence interval 1.1 to 1.7) and in patients with pulmonary embolism plus deep vein thrombosis (1.5, 1.1 to 1.9). In patients with distal deep vein thrombosis, the pooled rate of recurrent VTE per 100 person years was 1.9 events (95% confidence interval 0.5 to 4.3) in the first year after anticoagulation had stopped. The case fatality rate for recurrent VTE was 4% (95% confidence interval 2% to 6%).ConclusionsIn patients with a first episode of unprovoked VTE who completed at least three months of anticoagulant treatment, the risk of recurrent VTE was 10% in the first year after treatment, 16% at two years, 25% at five years, and 36% at 10 years, with 4% of recurrent VTE events resulting in death. These estimates should inform clinical practice guidelines, enhance confidence in counselling patients of their prognosis, and help guide decision making about long term management of unprovoked VTE.Systematic review registrationPROSPERO CRD42017056309.
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