Chest
Volume 141, Issue 2, Supplement, February 2012, Pages e419S-e496S
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Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physician Evidence-Based Clinical Practice Guidelines Online Only Articles
Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

https://doi.org/10.1378/chest.11-2301Get rights and content

Background

This article addresses the treatment of VTE disease.

Methods

We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence.

Results

For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C).

Conclusion

Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences.

Section snippets

Summary of Recommendations

Note on Shaded Text: Throughout this guideline, shading is used within the summary of recommendations sections to indicate recommendations that are newly added or have been changed since the publication of Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Recommendations that remain unchanged are not shaded.

2.1. In patients with acute DVT of the leg treated with vitamin K antagonist (VKA) therapy, we

Presentation as DVT or PE

In addressing DVT, we first review studies that included (1) only patients who presented with symptomatic DVT or (2) patients who presented with DVT or PE (ie, meeting the broader criterion of VTE). For the PE components, we review studies (and subgroups within studies) that required patients to have presented with symptomatic PE (who may also have had symptoms of DVT). For this reason and because more patients with VTE present with symptoms of DVT alone than with symptoms of PE (including

Initial Anticoagulation of Acute DVT of the Leg

The first and only randomized trial that compared anticoagulant therapy with no anticoagulant therapy in patients with symptomatic DVT or PE was published in 1960 by Barritt and Jordan.50 Trial results suggested that 1.5 days of heparin and 14 days of VKA therapy markedly reduced recurrent PE (0/16 vs 10/19) and appeared to reduce mortality (1/16 vs 5/19) in patients with acute PE. In the early 1990s, a single randomized trial established the need for an initial course of heparin in addition to

Long-term Anticoagulation of Acute DVT of the Leg

In this review, the term long-term treatment refers to treatments (eg, VKA therapy, LMWH, dabigatran) that are continued after initial therapy (eg, parenteral anticoagulation, thrombolytic therapy) (Fig 1). In addition, we consider treatment with rivaroxaban, which is used without initial parenteral therapy. Long-term therapy has two goals: (1) to complete treatment of the acute episode of VTE and (2) to prevent new episodes of VTE that are not directly related to the acute event. During the

PTS of the Leg

PTS is a cluster of leg symptoms and signs attributable to previous DVT. PTS occurs in about one-third of patients after acute DVT and up to two-thirds who have had an iliofemoral DVT.102, 232 The initial treatment of acute DVT, particularly with the use of thrombus removal strategies, may influence the risk of developing PTS (section 2.8). The most prominent symptoms are chronic dependent swelling and pain, discomfort on walking, and skin discoloration. The severity of symptoms may vary over

Initial Treatment of Acute PE

As we noted in Methods (section 1.1), recommendations for management of patients with PE, particularly those addressing anticoagulant therapy and IVC filter insertion, are based on studies that enrolled patients with only DVT, patients with both DVT and PE, and patients with only symptoms of PE. The following sections emphasize studies that enrolled only patients with symptoms of PE (who could also have symptoms of DVT), emphasize differences in the management of patients who present with PE

Long-term Treatment of PE

In the following sections, we emphasize studies that were performed exclusively in patients with PE and patients with PE who were enrolled in other studies. For the reasons noted in section 1.1, we make the same recommendations for long-term treatment of PE as for DVT and rate the quality of the underlying evidence as the same (see corresponding sections for treatment of DVT).

Chronic Thromboembolic Pulmonary Hypertension

Prospective studies suggest that CTPH occurs in ∼3% of patients who are treated for PE.104, 354, 355, 356, 357, 358 About one-third of patients have a history of VTE, whereas two-thirds have had single or recurrent episodes of PE that were not diagnosed and may have been asymptomatic.359 Patients with CTPH are likely to have a high risk of recurrent VTE because they have had previous VTE and have cardiopulmonary impairment. Recurrent VTE may be fatal more often in patients with severe

Superficial Vein Thrombosis

SVT has been less well studied than DVT but is estimated to occur more often.371, 372 It usually affects the lower limbs; often involves a varicose vein; is associated with chronic venous insufficiency, malignancy, thrombophilia, pregnancy or estrogen therapy, obesity, sclerotherapy, long-distance travel, and a history of VTE; or may be unprovoked.371, 372, 373 The long saphenous vein is involved in about two-thirds of lower-limb SVT.374

Although traditionally considered a benign disease, a

Acute Upper-Extremity DVT

About 5% to 10% of VTE involve the upper extremities.386, 387, 388, 389, 390 UEDVT includes two etiologic groups: primary (unprovoked with or without thrombophilia, effort-related and thoracic outlet syndrome) and secondary (provoked by central venous catheters, pacemakers, or cancer). Secondary UEDVT accounts for ∼75% of cases.386, 388, 389, 391, 392, 393, 394

UEDVT involves the subclavian, axillary, or brachial veins and may include extension to the brachiocephalic vein, superior vena cava, or

Splanchnic Vein Thrombosis

Thrombosis in the portal venous system, which includes the superior mesenteric, inferior mesenteric, splenic, and portal veins, is collectively termed splanchnic vein thrombosis. Depending on the location and extent of thrombosis, how rapidly thrombosis develops, speed and extent of thrombus recannulation, presence of collateral portal venous drainage, and adequacy of arterial inflow, splanchnic vein thrombosis may result in bowel or splenic infarction and chronic portal hypertension.425, 426,

Hepatic Vein Thrombosis

Hepatic vein thrombosis, particularly Budd-Chiari syndrome with occlusion of the main hepatic vein, can result in impairment of liver function and an associated coagulopathy.432, 433 Because there is limited understanding of the natural history of this condition and a paucity of prospective studies that have evaluated anticoagulant therapy, the role of anticoagulant therapy is uncertain.432

In a prospective registry of 163 patients with Budd-Chiari syndrome of variable extent, of whom 86% were

Future Research

Several questions in the treatment of VTE need to be answered. Current evidence relating to these questions is of moderate or low quality. We list the questions roughly as they arise in this article rather than in order of importance. We do not present the rationale for each question because this is addressed in the corresponding sections of the article. We have confined ourselves to the primary question (eg, Should patients with proximal DVT be treated with anticoagulant therapy alone, or

Acknowledgments

Author contributions: As Topic Editor, Dr Akl oversaw the development of this article, including the data analysis and subsequent development of the recommendations contained herein.

Dr Kearon: served as Deputy Editor.

Dr Akl: served as Topic Editor.

Dr Comerota: served as a panelist.

Dr Prandoni: served as a panelist.

Dr Bounameaux: served as a panelist.

Dr Goldhaber: served as a panelist.

Dr Nelson: served as a frontline clinician.

Dr Wells: served as a panelist.

Dr Gould: served as a resource

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    Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758] and Bayer Schering Pharma AG. Support in the form of educational grants were also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US.

    Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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