A variety of definitions of major bleeding have been used in published clinical studies, and this diversity adds to the difficulty in comparing data between trials and in performing meta‐analyses. In ...the first step towards unified definitions of bleeding complications, the definition of major bleeding in non‐surgical patients was discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Arising from that discussion, a definition was developed that should be applicable to studies with all agents that interfere with hemostasis, including anticoagulants, platelet function inhibitors and fibrinolytic drugs. The definition and the text that follows have been reviewed and approved by the cochairs of the subcommittee and the revised version is published here. The intention is to also seek approval of this definition from the regulatory authorities.
Four observations support that anticoagulant therapy for venous thromboembolism (VTE) has an ‘active treatment’ phase that is limited to about 3 months. First, <3 months of treatment is associated ...with a higher risk of recurrent VTE than treatment for 3 months or longer, suggesting that <3 months is inadequate therapy. Second, treatment for 3 months is associated with the same risk of recurrent VTE as treatment for 6 months or longer, suggesting that 3 months is adequate therapy. Third, the increase in recurrent VTE with too short a course of treatment is predominantly at the site of the initial thrombosis, suggesting reactivation of initial thrombosis. Fourth, the increase in recurrent VTE with too short a course of treatment occurs immediately after treatment is stopped and is short lived, again suggesting reactivation of initial thrombosis. Once the initial thrombosis has been adequately treated (i.e. the first phase of treatment), further anticoagulation serves as ‘secondary prevention’ of new, unrelated, episodes of thrombosis (i.e. the second phase of treatment). For most patients, therefore, anticoagulant therapy for VTE should be stopped at 3 months when the acute episode has completed treatment, or should be continued indefinitely as ‘secondary prevention’ if the risk of recurrence remains unacceptably high having completed ‘active treatment’.
The post‐thrombotic syndrome (PTS) is increasingly recognized to be a common and important complication of deep venous thrombosis (DVT). Because there is no ‘gold standard’ objective test to ...establish its presence, PTS is diagnosed primarily on the basis of the presence of typical symptoms and clinical signs in a limb that was affected by DVT. As a wide variety of definitions of PTS have been used by researchers, it is difficult to compare data across studies and to formally combine data in meta‐analyses. In a step towards standardization of the measurement of PTS in clinical studies, available scales and evidence to support their utility to diagnose PTS and to classify its severity were reviewed and discussed at the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis (Vienna, July 2008).
SUMMARY POINTS Assessment of clinical pre-test probability (CPTP) is the first step in the diagnosis of pulmonary embolism Combinations of CPTP and test results are usually needed to identify ...patients who require, and do not require, anticoagulant therapy Thrombolytic therapy is usually reserved for patients with hypotension and without major risk factors for bleeding Pulmonary embolism associated with a reversible risk factor is usually treated for three months Pulmonary embolism associated with active cancer, or a second unprovoked pulmonary embolism, is usually treated indefinitely The decision to treat an unprovoked pulmonary embolism for three months or indefinitely is sensitive to an individual patient's preference and risk of bleeding
Objective To determine how length of anticoagulation and clinical presentation of venous thromboembolism influence the risk of recurrence after anticoagulant treatment is stopped and to identify the ...shortest length of anticoagulation that reduces the risk of recurrence to its lowest level.Design Pooled analysis of individual participants’ data from seven randomised trials.Setting Outpatient anticoagulant clinics in academic centres.Population 2925 men or women with a first venous thromboembolism who did not have cancer and received different durations of anticoagulant treatment.Main outcome measure First recurrent venous thromboembolism after stopping anticoagulant treatment during up to 24 months of follow-up.Results Recurrence was lower after isolated distal deep vein thrombosis than after proximal deep vein thrombosis (hazard ratio 0.49, 95% confidence interval 0.34 to 0.71), similar after pulmonary embolism and proximal deep vein thrombosis (1.19, 0.87 to 1.63), and lower after thrombosis provoked by a temporary risk factor than after unprovoked thrombosis (0.55, 0.41 to 0.74). Recurrence was higher if anticoagulation was stopped at 1.0 or 1.5 months compared with at 3 months or later (hazard ratio 1.52, 1.14 to 2.02) and similar if treatment was stopped at 3 months compared with at 6 months or later (1.19, 0.86 to 1.65). High rates of recurrence associated with shorter durations of anticoagulation were confined to the first 6 months after stopping treatment.Conclusion Three months of treatment achieves a similar risk of recurrent venous thromboembolism after stopping anticoagulation to a longer course of treatment. Unprovoked proximal deep vein thrombosis and pulmonary embolism have a high risk of recurrence whenever treatment is stopped.
Background: Fatal bleeding is a serious consequence of anticoagulant therapy, but factors associated with fatal bleeding during the first 3 months of treatment of venous thromboembolism (VTE) are ...uncertain. Methods: Using data from RIETE, an ongoing registry of consecutive patients with acute VTE, we assessed risk factors for fatal bleeding among all patients. We then used this information to derive a clinical model that would stratify a patient’s risk of fatal bleeding during the first 3 months of treatment. Results: Of 24 395 patients, 546 (2.24%) had a major bleed and 135 (0.55%) had a fatal bleed. The gastrointestinal tract was the most common site (40% of fatal bleeds), followed by intracranial bleeding (25%). Fatal bleeding was independently associated with the following factors at the time of VTE diagnosis: age >75 years (OR, 2.16), metastatic cancer (OR, 3.80), immobility ≥ 4 days (OR, 1.99), a major bleed within the past 30 days (OR, 2.64), an abnormal prothrombin time (OR, 2.09), a platelet count < 100 × 109 L−1 (OR, 2.23), creatinine clearance < 30 mL min−1 (OR, 2.27), anemia (OR, 1.54), and distal deep vein thrombosis (OR, 0.39). INR at the time of bleeding is not known. A clinical prediction rule for risk of fatal bleeding that included nine baseline factors was derived. Fatal bleeding occurred in 0.16% (95% CI, 0.11–0.23) of the low‐risk, 1.06% (95% CI, 0.85–1.30) of the moderate‐risk, and 4.24% (95% CI, 2.76–6.27) of the high‐risk category. Conclusions: Patient characteristics and laboratory variables can identify patients at high risk for fatal bleeding during treatment of VTE.
About half of the patients with a first idiopathic proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) are expected to have a recurrent episode of venous thromboembolism (VTE) within 10 ...years of stopping therapy, and randomized trials have shown that this group of patients benefit from long‐term anticoagulant therapy. High risks for bleeding and patient preference are compelling reasons not to treat such patients long‐term. Although a number of factors are associated with a reduced risk of recurrence, they require further validation before it is appropriate to routinely stop anticoagulants after 3 months in patients with idiopathic proximal DVT or PE.
Background
Although venous thromboembolism (VTE) is an important cause of postoperative morbidity and mortality, there is still no consensus on the optimal strategy for VTE prevention after major ...surgery. The objective of this review was to determine the benefits and risks of thromboprophylaxis with both compression and anticoagulation, compared with either modality alone.
Methods
A systematic review of MEDLINE, CENTRAL and Embase databases was performed to identify eligible randomized trials. The literature search and data extraction were carried out independently by two reviewers. Outcomes of interest were deep vein thrombosis (DVT), pulmonary embolism, bleeding, limb injury and mortality.
Results
Twenty‐five studies were eligible for inclusion. Adding compression to anticoagulation decreased the risk of DVT by 49 per cent (risk ratio (RR) 0·51, 95 per cent confidence interval 0·36 to 0·73). The corresponding funnel plot suggested publication bias and, overall, the evidence for this comparison was judged to be of low quality. Adding anticoagulation to compression decreased the risk of DVT by 44 per cent (RR 0·56, 0·45 to 0·69) while increasing the risk of bleeding (RR 1·74, 1·29 to 2·34). There was no suggestion of publication bias and the evidence for this comparison was judged to be of moderate quality.
Conclusion
Combined compression and anticoagulation is more effective at preventing postoperative DVT than either modality alone. However, adding anticoagulation to compression increases the risk of bleeding, and the evidence that adding compression to anticoagulation reduces VTE risk is of low quality.
Best in combination
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