Venous Thromboembolism: Diagnosis and Treatment.

Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH

D-dimer testing after anticoagulant discontinuation to predict recurrent venous thromboembolism

Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline

Quality Improvement Guidelines for the Treatment of Lower Extremity Deep Vein Thrombosis with Use of Endovascular Thrombus Removal

Influence of Preceding Length of Anticoagulant Treatment and Initial Presentation of Venous Thromboembolism on Risk of Recurrence After Stopping Treatment: Analysis of Individual Participants' Data From Seven Trials

Long‐term low‐dose warfarin use is effective in the prevention of recurrent venous thromboembolism: no

Venous thromboembolism (VTE) has been traditionally considered a transient acute disorder requiring a limited duration of anticoagulant therapy. Patients who suffer deep vein thrombosis (DVT) or pulmonary embolism (PE) following major surgery, major trauma, or periods of immobility are generally treated with anticoagulation for 3–6 months. After completion of anticoagulation for the initial event, the risk of VTE recurrence is believed to return to that of the general population. However, epidemiological studies suggest that VTE may be better characterized as a chronic disorder with periodic relapses. While patients who suffer unprovoked (idiopathic) VTE bear the highest risk of recurrent events, exceeding 50% over 10 years if not treated with extended duration anticoagulation, those who suffer VTE in the setting of identifiable provoking factors have an enduring risk of recurrence that exceeds 20% over 10 years. 1 Randomized controlled trials of extended duration anticoagulation for prevention of recurrent unprovoked VTE have demonstrated that the rate of recurrence increases abruptly if anticoagulation is discontinued. 2 An analysis of the Danish National Registry of Patients demonstrated that patients with VTE have increased mortality over 30 years of follow-up and that recurrent PE is an important cause of death throughout this period. 3 The efficacy of extended duration anticoagulation for prevention of recurrent events after an initial unprovoked DVT or PE further supports the classification of VTE as a chronic relapsing disease. Prolonged anticoagulation with a low- (international normalized ratio (INR) target 1.5–2.0) 4 or conventional-intensity (INR target 2.0–3.0) 5 or a non-vitamin K-dependent oral anticoagulant such as rivaroxaban, 6 dabigatran, 2 or apixaban 7 provides a 60–90% reduction in recurrent events in patients who suffer an initial unprovoked VTE. Evidence-based practice guidelines recognize the increased risk of recurrence among patients with idiopathic VTE and recommend extended duration anticoagulation in those with a low bleeding risk. Virchow’s Triad of stasis, hypercoagulability, and endothelial dysfunction and injury does not fully explain the increased risk of recurrent VTE and the need for extended duration anticoagulation. Immobility resulting in stasis is only a transient risk factor in the majority of patients with VTE. Although frequently sought as an explanation for VTE, thrombophilia is detected in only a minority of patients. 8 Furthermore, common thrombophilias such as the factor V Leiden and prothrombin gene mutations do not appear to increase the risk of recurrence. 8 Endothelial dysfunction and injury may play an important role in a subset of patients with VTE, but the underlying mechanism leading to recurrence remains unclear. Advances in our understanding of the pathophysiology of atherothrombosis may shed light on critical mechanisms for VTE recurrence. Traditionally, the burden of recurrent atherothrombotic events has been largely ascribed to dyslipidemia. However, even with intensive lipid-lowering therapy for secondary prevention, a significant burden of recurrent atherothrombotic events remains. A growing body of literature suggests that cardiovascular inflammation is a key pathophysiologic factor in recurrent atherothrombotic events. 9,10 Traditionally considered distinct and unrelated disorders, atherothrombosis and VTE are linked both epidemiologically and pathophysiologically. In fact, a reciprocal relationship exists: patients with VTE have an increased risk of myocardial infarction and stroke, and vice versa. Proven cardiovascular risk factors such as obesity, tobacco use, diabetes, stress, and diet increase the risk of atherothrombotic events and VTE. These particular risk factors share a common pathophysiological mechanism of promoting cardiovascular inflammation. In epidemiologic studies, systemic inflammation has been closely associated with an increased risk of VTE. The increased frequency of DVT and PE in patients with chronic inflammatory disorders such as inflammatory bowel disease and systemic vasculitis highlights the role of inflammation in VTE. Furthermore, increased levels of the inflammatory biomarker C-reactive protein (CRP) are associated with an increased risk of VTE. In an analysis of 10,505 participants in

Fixed-dose low-molecular-weight heparin, bemiparin, in the long-term treatment of venous thromboembolism in patients with transient risk factors in standard clinical practice: the FLEBUS study.

Real world experience at a single centre using low dose direct oral anticoagulants after unprovoked venous thromboembolism.

Identification of outcomes in clinical studies of interventions for venous thromboembolism in non‐pregnant adults

Identification of Patients with Unprovoked Venous Thromboembolism and a Low Risk of Recurrence Estimated By the Vienna Prediction Model: A Prospective Cohort Management Study

Recurrent Deep Vein Thrombosis: Long-Term Incidence and Natural History

A large number of individuals develop venous thromboembolism (VTE) every year.1 Each patient’s episode of DVT or PE is, naturally, unique. To highlight a variety of aspects about VTE a compilation case is presented that is composed of clinical data and images from several real patients. ### History of Present Illness A 36-year-old woman presents to the Emergency Department with severe shortness of breath and moderately intense anterior chest pain, worse on deep inspiration, which had started suddenly that morning. She also reports a 6-wk history of mild shortness of breath, for which she had been seen 4 wk earlier by her primary care physician who diagnosed her with “asthma.” Bronchodilators and steroids were prescribed but led to no significant improvement in her symptoms. She also gives a history of mild left calf pain that had started about 2 months earlier without preceding trauma, immobilization, or surgery. Her primary care physician had seen her and prescribed Ibuprofen for a “pulled muscle.” However, in the 1 week before her present presentation her leg symptoms worsened, and she had increased diffuse leg pain and swelling and slightly bluish discoloration of the whole leg. Her past medical history is only significant for an appendectomy at age 16. She has never been pregnant. She is on no medications, except for an estrogen and progestin-containing oral contraceptive, started 10 months earlier. She does not smoke. There is no family history of venous thromboembolism, although the patient reports that her paternal grandmother had a “swollen leg for many years” until she died in her 70’s, but no further details are known of the patient. ### Physical Examination The patient’s weight is 86 kg and her height 165 cm, calculating to a body mass index (weight divided by [height in meters]2) of 31.6 kg/m2, ie, she has grade 1 obesity. Her …

Predictors and Outcomes of Recurrent Venous Thromboembolism in Elderly Patients

BackgroundPatients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended “life-long” anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a “weak provoking factor” there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event.ObjectiveA systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued.Data SourcesMEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles.Study SelectionRandomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy.Data ExtractionIndependent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent.Data SynthesisSeven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11–0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69–3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40–1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm.ConclusionsVKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients’ risk for recurrent PE as well as the patients’ values and preferences.