Thrombosis in Clinical Practice

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While the appropriate duration of anticoagulation for idiopathic or recurrent VTE is not definitively known, there is evidence of substantial benefit for extended-duration therapy. For VTE secondary to transient risk factors, 3 or 6 months of treatment was associated with similar risks for recurrent VTE. Length of therapy in the trials varied widely, from greater than 3 months to 12 months to up to 4 years. The results for extended-duration therapy reflect follow-up only to 4 years; the risk-benefit ratio is not known for longer durations.

Clinicians should weigh the benefits, harms, and patient preferences in deciding on the duration of anticoagulation. LMWH is safe and efficacious for the long-term treatment of VTE in selected patients and may be preferable for patients with cancer.

Venous Thromboembolism

Evidence from high-quality randomized trials supports the use of LMWH as comparable to oral anticoagulation for VTE in selected patients. Low-molecular-weight heparin may be a useful treatment for patients in whom control of the international normalized ratio INR is difficult, and may be more efficacious than oral anticoagulants in patients with cancer. Deep venous thrombosis in the lower extremities is the most frequent manifestation of VTE, and the most life-threatening manifestation is pulmonary embolism.

An important complication of DVT is postthrombotic syndrome, which may result in life-long limb pain and edema. The intent of this guideline is to provide evidence-based recommendations for management of VTE.

The target audience is all clinicians caring for patients who have received a diagnosis of DVT or pulmonary embolism. The target patient population is patients given a diagnosis of pulmonary embolism or lower-extremity DVT. Recommendations are based only on evidence from high-quality randomized trials unless otherwise stated. Diagnosis of VTE is the other guideline and is covered in a paper by Qaseem and colleagues.

Those papers contain substantial additional detail about the evidence for each of the recommendations in this guideline. The EPC authors reviewed the evidence that was available to answer each of these questions. This evidence is summarized below. The EPC authors found 16 systematic reviews of randomized trials that reviewed rates of recurrent venous thromboembolism, major bleeding, or death. Patients treated with LMWH had significantly fewer episodes of bleeding than those treated with unfractionated heparin.

Nine of 10 reviews showed that LMWH significantly reduced mortality during the 3 to 6 months of follow-up compared with unfractionated heparin. In summary, the evidence suggests that LMWH is superior to unfractionated heparin for the treatment of DVT of the lower extremities, particularly for reducing mortality and the risk for major bleeding during initial therapy.

It is at least as safe and effective as unfractionated heparin for patients with pulmonary embolism. Twelve studies compared the outcomes of patients with VTE treated with LMWH administered at home to the outcomes of those treated with unfractionated heparin in the hospital.

An additional 5 studies, including 2 randomized trials, 25 , 26 compared outcomes and costs for patients receiving LMWH at home to those for patients receiving LWMH administered in the hospital. Seven of the studies allowed a brief inpatient admission for stabilization of the patients before randomization to the outpatient group. Four of these studies enrolled patients with concomitant pulmonary embolism.

Diagnosis and management of iliofemoral deep vein thrombosis: clinical practice guideline | CMAJ

Most studies excluded patients with previous VTE, thrombophilic conditions, or significant comorbid illnesses; pregnant patients; and patients unlikely to adhere to outpatient therapy. Very few studies reported on the adequacy of anticoagulation in the unfractionated heparin groups or after transition from heparin to warfarin. All the studies were carried out in settings with well-developed patient education and home care support infrastructures.

The rates of recurrent DVT in the different treatment groups differed only slightly. Fewer inpatient days accrued in the LMWH treatment groups. Ten of these 17 studies reported on treatment costs, 9 , 10 , 16 , 20 — 22 , 24 — 26 , 28 and 9 found the outpatient strategy cost-saving compared with inpatient therapy. For more in-depth analysis of the cost-effectiveness of initial outpatient therapy, please see the Appendix available at www. In summary, there is consistent evidence that outpatient treatment of VTE with LMWH is cost-saving and at least as safe as inpatient treatment among highly selected patients in settings where the required support services are in place.

There is no standardized definition of postthrombotic syndrome, but most descriptions include chronic postural dependent edema and pain or localized discomfort in a patient with previous venous thrombosis. Three randomized controlled trials have examined the efficacy of compression stockings for prevention of postthrombotic syndrome after DVT, but only 2 examined their use within the first month after diagnosis. The evidence suggests that the use of compression stockings starting from 1 month of diagnosis or earlier and lasting 2 years after DVT diagnosis reduces the incidence and severity of postthrombotic syndrome.


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The absolute risk for symptomatic VTE during pregnancy is between 0. There is not adequate evidence for definitive recommendations for management of VTE in pregnancy. The EPC authors restricted their review to 10 trials, all published since , that used objective radiologic documentation of VTE and measured therapeutic intensity by INR. The rates of recurrent DVT in these trials varied tremendously depending on whether the enrolled patients had had idiopathic DVT, 48 , 49 , 51 , 53 DVT in the setting of a transient risk factor, 54 a permanent risk factor for recurrent DVT, or a history of multiple previous thromboses.

Result Filters

In a pooled analysis of the 4 trials of VTE that compared 3 or fewer months to 4 to 12 months of therapy, 46 , 49 , 50 , 52 there was a trend toward fewer recurrences with longer treatment, although the confidence interval included 1. The results were largely driven by a single study that randomly assigned patients to 6 weeks or 6 months of therapy. A trial of indefinite-duration low-dose anticoagulation after 6 months of full-dose anticoagulation for idiopathic VTE 48 was terminated at 4 years because clear evidence of benefit made it unethical to continue randomly assigning patients to placebo absolute risk reduction for recurrent VTE, 4.

Seven studies 46 — 48 , 50 , 51 , 53 , 54 enrolled patients with pulmonary embolism, 52 but only 1 focused exclusively on patients with pulmonary embolism. In that study, 6 to 12 months of therapy 6 months for patients with transient risk factors or 12 months for those with an idiopathic event and 3 to 6 months of abbreviated therapy 3 months for patients with transient risk factors or 6 months for those with an idiopathic event were associated with similar risks for recurrent VTE 3. Four studies addressed the intensity of anticoagulation.

The evidence best supports conventional-intensity therapy INR, 2 to 3 for 3 to 6 months among patients with VTE secondary to transient risk factors, at least 12 months among patients with a second episode of VTE, and extended-duration conventional-intensity oral anticoagulation among patients with idiopathic events.

The results for extended-duration therapy reflect follow-up only to 4 years; the risk-benefit ratio of continuous, conventional anticoagulation may change with longer treatment. The EPC authors identified 9 well-designed randomized, controlled trials 55 — 63 and 1 large, prospective cohort study 64 that compared the safety and efficacy of LWMH with those of oral vitamin K antagonists for the full course of treatment of VTE. All studies were open-label, eligibility criteria were somewhat restrictive thereby limiting generalizability , and most studies lasted 3 months.

The percentage of time that the INR was in a therapeutic range was not particularly high and probably mirrors clinical practice. The rates of recurrence of VTE did not substantially differ, and in no trial did the bleeding rates in the LMWH group exceed those in the oral anticoagulant group. Low-molecular-weight heparin is an option for patients in whom INR control is difficult, and it may be more efficacious than oral anticoagulants in patients with cancer.

A single randomized trial addressed this question. However, filters were associated with a significant increase in recurrent DVT compared with anticoagulation alone This study provides no information about the effectiveness of filters for patients who do not receive anticoagulation, for whom filter placement is typically considered.

An observational cohort study used administrative data to assess patients with VTE who did and did not receive vena cava filters during a 5-year period.


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  • The time to recurrent pulmonary embolism was similar in filter recipients and nonrecipients. Overall, there is insufficient evidence to make recommendations in this area. Catheter-directed thrombolysis involves administration of thrombolytics directly through the side ports of a catheter traversing the thrombus. Only 1 small randomized trial has compared catheter-directed thrombolysis with conventional sequenced heparin and warfarin in patients with acute iliofemoral DVT. Most other studies of catheter-directed thrombolysis are observational studies or case series.

    Financial support for the development of this guideline comes exclusively from the American College of Physicians and American Academy of Family Physicians operating budgets. The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of the Agency for Healthcare Research and Quality or the U. Department of Health and Human Services.

    This guideline is endorsed by the Canadian Interventional Radiology Association. We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Skip to main content. Boniface Hospital, Winnipeg, Man.

    Scope This guideline is intended to assist Canadian primary care physicians in the assessment and management of patients with iliofemoral DVT. Methods This consensus guideline provides recommendations on the diagnosis and management of iliofemoral DVT, including the use of anticoagulation, thrombus removal strategies and inferior vena cava filters, as well as the treatment of post-thrombotic syndrome.

    Use of IVC filters 3. Use of venous stenting 7. Management of post-thrombotic syndrome 8. Panel composition A multidisciplinary working group of 13 members, assembled under the auspices of the University of British Columbia Departments of Radiology and Internal Medicine, consisted of five hematologists E. Management of conflicts of interest Panel members disclosed financial and intellectual conflicts of interest. Development of recommendations Content experts on the panel participated in a series of teleconferences and email correspondence to determine the scope and topics to be addressed by the guideline.

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    Recommendations The recommendations are summarized in Box 2 , and a decision algorithm is provided in Figure 1. Patients with cancer In patients with cancer, low-molecular-weight heparin is the recommended agent for both initial and long-term management of venous thromboembolism. Inferior vena cava filters Despite the widespread use of inferior vena cava filters, robust data on their efficacy and safety are limited to two randomized controlled trials in which anticoagulant therapy was administered concurrently. Clot removal and reduction strategies The goals of clot removal and reduction strategies are to normalize venous circulation, preserve venous valves, preserve the limb and prevent post-thrombotic syndrome.

    Patients with phlegmasia cerulea dolens Given the rarity of phlegmasia cerulea dolens, no high-quality data are available to support the use of clot removal and reduction strategies for patients with this condition. Patients without phlegmasia cerulea dolens In patients with iliofemoral DVT without phlegmasia cerulea dolens, early clot removal and recanalization may reduce the risk of post-thrombotic syndrome by improving venous patency and preserving venous valvular function.

    Surgical thrombectomy Evidence for surgical thrombectomy for the treatment of iliofemoral DVT is limited to one small randomized trial and a meta-analysis of observational studies that suggested improved vein patency and valve function and fewer symptoms of post-thrombotic syndrome. Endovascular thrombus removal Endovascular thrombus removal provides targeted thrombolytic therapy that reduces the complications associated with systemic administration of thrombolytics.

    Post-thrombotic syndrome Iliofemoral DVT is one of the strongest risk factors for post-thrombotic syndrome, the most common complication of DVT. Prevention of post-thrombotic syndrome Initial RCTs of compression therapy for the prevention of post-thrombotic syndrome in patients with proximal DVT including iliofemoral DVT yielded conflicting results, but were hindered by lack of a placebo control, small numbers of patients, single-centre recruitment and open-label design. Treatment of post-thrombotic syndrome There is limited evidence for any effective treatment for established post-thrombotic syndrome.

    Implementation This guideline has been endorsed by the Canadian Interventional Radiology Association, with plans for additional dissemination of information through a series of publications in specialty-specific journals and case reports. Other guidelines Guidelines have been published recently by the American Heart Association in 18 and the American College of Chest Physicians in Gaps in knowledge Early RCT data have provided evidence of modest effect of clot removal strategies for the prevention of post-thrombotic syndrome.

    Conclusion Relative to femoropopliteal or distal DVT, iliofemoral DVT carries a higher risk of phlegmasia cerulea dolens, recurrent venous thromboembolism and post-thrombotic syndrome. Key points Ultrasonography is the diagnostic imaging modality of choice for patients with suspected deep vein thrombosis DVT.

    This article has been peer reviewed. The epidemiology of venous thromboembolism. Circulation ; 23 Suppl 1: Quality improvement guidelines for the treatment of lower extremity deep vein thrombosis with use of endovascular thrombus removal. J Vasc Interv Radiol ; 20 7 Suppl: Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med ; Does the location of thrombosis determine the risk of disease recurrence in patients with proximal deep vein thrombosis? Am J Med ; How I treat postthrombotic syndrome. Blood ; Thrombolysis for acute deep vein thrombosis.

    Cochrane Database Syst Rev ; 4: Pooled analyses of randomized trials of streptokinase and heparin in phlebographically documented acute deep venous thrombosis. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis the CaVenT study: Lancet ; Long-term results of venous thrombectomy combined with a temporary arteriovenous fistula. Eur J Vasc Surg ; 4: Thrombectomy with temporary arteriovenous fistula: J Vasc Surg ; 1: Venous thrombectomy for iliofemoral vein thrombosis — year results of a prospective randomised study.

    Eur J Vasc Endovasc Surg ; BMJ ; Incorporating considerations of resources use into grading recommendations. Going from evidence to recommendations. J Am Coll Cardiol ; Circulation ; Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 1 of 3. Allergy ; Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. CMAJ ; Am J Public Health ; Hirsh J , Lee AY. How we diagnose and treat deep vein thrombosis.

    American College of Chest Physicians evidence-based clinical practice guidelines. Chest ; 2 Suppl: Trends in management of phlegmasia cerulea dolens. Vasc Endovascular Surg ; The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev ; 9: Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis: Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: Oral rivaroxaban for symptomatic venous thromboembolism.

    N Engl J Med ; Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: Thromb J ; Dabigatran versus warfarin in the treatment of acute venous thromboembolism. Oral apixaban for the treatment of acute venous thromboembolism. Antithrombotic therapy for VTE disease: A single, randomized trial addressed this question After 2 years of follow-up, filter placement with anticoagulation was associated with a slight reduction in symptomatic pulmonary embolism compared with anticoagulation alone.

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    However, filters were associated with a significant increase in recurrent DVT compared with anticoagulation alone This study provides no information about the effectiveness of filters for patients who do not receive anticoagulation, for whom filter placement is typically considered. An observational cohort study used administrative data to assess patients with VTE who did and did not receive vena cava filters during a 5-year period After adjustment for risk factors associated with recurrent VTE, filter placement did not reduce pulmonary embolism but was associated with a 2-fold increase in the relative hazard of subsequent DVT among patients with initial pulmonary embolism.

    The time to recurrent pulmonary embolism was similar in filter recipients and nonrecipients. Overall, there is insufficient evidence to make recommendations in this area. Catheter-directed thrombolysis involves administration of thrombolytics directly through the side ports of a catheter traversing the thrombus. Only 1 small randomized trial has compared catheter-directed thrombolysis with conventional, sequenced heparin and warfarin in patients with acute iliofemoral DVT Six months after treatment, the patency rate was significantly higher in the group that received catheter-directed thrombolysis, and the prevalence of venous reflux was lower.

    Most other studies of catheter-directed thrombolysis are observational studies or case series 68— While these studies suggest that catheter-directed thrombolysis may be efficacious in well-chosen patients, the evidence is insufficient to make recommendations. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: Recurrent venous thromboembolism after deep vein thrombosis: Current diagnosis of venous thromboembolism in primary care: Diagnosis and treatment of deep venous thrombosis and pulmonary embolism.

    Evid Rep Technol Assess Summ. Assessing the quality of reports of randomized clinical trials: Strength of recommendation taxonomy SORT: Should low-molecular-weight heparins replace unfractionated heparin as the agent of choice for adults with deep venous thrombosis? Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism.

    Low molecular weight heparins LMWH in the treatment of patients with acute venous thromboembolism. Suboptimal monitoring and dosing of unfractionated heparin in comparative studies with low-molecular-weight heparin. Do the low molecular weight heparins improve efficacy and safety of the treatment of deep venous thrombosis? Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev. For the initial treatment of venous thromboembolism: Comparison of low-molecular-weight heparin, administered primarily at home, with unfractionated heparin, administered in hospital, and subcutaneous heparin, administered at home for deep-vein thrombosis.

    Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. An outpatient program to treat deep venous thrombosis with low-molecular-weight heparin. Outpatient treatment of venous thromboembolism with low-molecular-weight heparin: Home treatment of deep venous thrombosis with low molecular weight heparin: Long-term incidence of recurrent venous thromboembolism.

    Outpatient treatment of deep venous thrombosis: Cost comparison of at-home treatment of deep venous thrombosis with low molecular weight heparin to inpatient treatment with unfractionated heparin. Direct medical cost of managing deep vein thrombosis according to the occurrence of complications. Management of acute proximal deep vein thrombosis: Outpatient management of DVT using low molecular weight heparin and a hospital outreach service. Management of venous thromboembolism: Comparison of urokinase, alteplase, and reteplase for catheter-directed thrombolysis of deep venous thrombosis.

    Reteplase in the treatment of peripheral arterial and venous occlusions: Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: Low molecular weight heparin versus warfarin in the prevention of recurrences after deep vein thrombosis. Low molecular weight heparin enoxaparin versus oral anticoagulant therapy acenocoumarol in the long-term treatment of deep venous thrombosis in the elderly: Low molecular weight heparin versus acenocoumarol in the secondary prophylaxis of deep vein thrombosis.

    Secondary prevention of venous thromboembolism: A role for low-molecular-weight heparin. Tinzaparin sodium for thrombosis treatment and prevention during pregnancy. Venous thromboembolism during pregnancy: Endovascular caval interruption in pregnant patients with deep vein thrombosis of the lower extremity. Management of deep vein thrombosis of the lower extremity in pregnancy: Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis.

    Prevention and treatment of postphlebitic syndrome: Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. N Engl J Med. A population-based study of the effectiveness of inferior vena cava filter use among patients with venous thromboembolism. The role of vena caval filters in the management of venous thromboembolism.

    Optimal duration of oral anticoagulant therapy: A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis.

    Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. Extended oral anticoagulant therapy after a first episode of pulmonary embolism.

    Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor. Low-molecular-weight heparin versus warfarin for prevention of recurrent venous thromboembolism: Venographic comparison of subcutaneous low-molecular weight heparin with oral anticoagulant therapy in the long-term treatment of deep venous thrombosis.

    Low-molecular-weight heparin in the acute and long-term treatment of deep vein thrombosis.