Sections

Treatment

Approach Considerations

The primary objectives for the treatment of deep venous thrombosis (DVT) are to prevent pulmonary embolism (PE), reduce morbidity, and prevent or minimize the risk of developing the postthrombotic syndrome (PTS).

The mainstay of medical therapy has been anticoagulation since the introduction of heparin in the 1930s.^[112]Other anticoagulation drugs have subsequently been added to the treatment armamentarium over the years, such as vitamin K antagonists and low-molecular-weight heparin (LMWH). More recently, mechanical thrombolysis has become increasingly used as endovascular therapies have increased. Absolute contraindications to anticoagulation treatment include intracranial bleeding, severe active bleeding, recent brain, eye, or spinal cord surgery, pregnancy, and malignant hypertension. Relative contraindications include recent major surgery, recent cerebrovascular accident, and severe thrombocytopenia.

The immediate symptoms of DVT often resolve with anticoagulation alone, and the rationale for intervention is often reduction of the 75% long-term risk of PTS. Systemic IV thrombolysis once improved the rate of thrombosed vein recanalization; however, it is no longer recommended because of an elevated incidence of bleeding complications, slightly increased risk of death, and insignificant improvement in PTS. The lack of a significantly reduced incidence of PTS after systemic thrombolysis (40-60%) likely reflects the inadequacy of the relatively low threshold volume of thrombus removal that was considered successful.

Thrombolytic therapy is recommended (systemic preferred over catheter directed) in hypotensive individuals with an acute PE.^[113] Those with high-risk PE presenting in shock should undergo systemic thrombolysis; when thrombolysis is contraindicated owing to a high risk of bleeding, consider surgical thrombectomy or catheter direct thrombolysis.^[114]

The bleeding risk of systemic thrombolysis is similar to that of catheter-directed thrombolysis, and the risk of PTS may further decrease risk. However, whether catheter-directed thrombolysis is preferred to anticoagulation has not been examined. The addition of percutaneous mechanical thrombectomy to the interventional options may facilitate decision-making, because recanalization may be achieved faster than before and with a decreased dose of lytic; therefore, the bleeding risk may be decreased.

Inpatient Versus Outpatient Treatment

Acute DVT may be treated in an outpatient setting with LMWH. Patients with low-risk PE may be safely discharged early from hospital or receive only outpatient treatment with LMWH, followed by vitamin K antagonists, although nonvitamin K-dependent oral anticoagulants may be as effective but safer than the LMWH/vitamin K antagonist regimen.^[115]

Anticoagulant therapy is recommended for 3-12 months depending on site of thrombosis and on the ongoing presence of risk factors. If DVT recurs, if a chronic hypercoagulability is identified, or if PE is life threatening, lifetime anticoagulation therapy may be recommended. This treatment protocol has a cumulative risk of bleeding complications of less than 12%.

Most patients with confirmed proximal vein DVT may be safely treated on an outpatient basis. Exclusion criteria for outpatient management are as follows:

Suspected or proven concomitant PE
Significant cardiovascular or pulmonary comorbidity
Iliofemoral DVT
Contraindications to anticoagulation
Familial or inherited disorder of coagulation: antithrombin III (ATIII) deficiency, prothrombin 20210A, protein C or protein S deficiency, or factor V Leiden
Familial bleeding disorder
Pregnancy
Morbid obesity (>150 kg)
Renal failure (creatinine >2 mg/dL)
Unavailable or unable to arrange close follow-up care
Unable to follow instructions
Homeless
No contact telephone
Geographic (too far from hospital)
Patient/family resistant to outpatient therapy

Admitted patients may be treated with a LMWH, fondaparinux, or unfractionated heparin (UFH). Warfarin 5 mg PO daily is initiated and overlapped for about 5 days until the international normalized ratio (INR) is therapeutic >2 for at least 24 hours.

For admitted patients treated with UFH, the activated partial thromboplastin time (aPTT) or heparin activity level must be monitored every 6 hours while the patient is taking intravenous (IV) heparin until the dose is stabilized in the therapeutic range. Patients treated with LMWH or fondaparinux do not require monitoring of the aPTT.

Platelets should be monitored. Heparin or LMWH should be discontinued if the platelet count falls below 75,000. Fondaparinux is not associated with hepatin-induced thrombocytopenia (HIT).

Consultations

Consultations with the following specialists are indicated:

Hematologist
Vascular surgeon
Radiologist
Interventional radiologist

General Principles of Anticoagulation

Anticoagulant therapy remains the mainstay of medical therapy for deep venous thrombosis (DVT) because it is noninvasive, it treats most patients (approximately 90%) with no immediate demonstrable physical sequelae of DVT, it has a low risk of complications, and its outcome data demonstrate an improvement in morbidity and mortality. Long-term anticoagulation is necessary to prevent the high frequency of recurrent venous thrombosis or thromboembolic events. Anticoagulation does have problems. Although it inhibits propagation, it does not remove the thrombus, and a variable risk of clinically significant bleeding is observed.

First-line therapy for non-high risk venous thromboembolism (VTE) or pulmonary embolism (PE) consists of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, or edoxaban) over vitamin K antagonists (VKAs).^{[113, 114]} VKAs are also recommended over low-molecular-weight heparin (LMWH), unless VTE is associated with malignancy, in which case LMWH is preferred over VKAs or any direct oral anticoagulants.^[113]

When the risk of VTE recurrence is high in patients with subsegmental PE without DVT, the American College of Chest Physicians (ACCP) recommends anticoagulation over surveillance; when the VTE recurrence risk is low in these patients, surveillance over anticoagulation is suggested.^[113]

Inferior vena cava filters are not recommended in patients with acute VTE on anticoagulant therapy.^[113]

Barring contraindications to aspirin therapy, aspirin is recommended to prevent recurrent VTE in patients with an unprovoked proximal DVT or PE following anticoagulation cessation.^[113]

Park and Byun indicate that possibilities for advances in anticoagulant delivery systems include expansion of new oral agents and their antidotes, reducing the size of heparins, developing oral or topical heparins, and modifying physical or chemical formulations.^[116] For example, Ita suggests that transdermal delivery may potentially bypass known issues with heparin use, such as short half-life and unpredictable bioavailability, and offer improved patient compliance, convenience, ease of dosing termination, as well as avoid the first-pass effect.^[112]

For more information, see General Principles of Anticoagulation in Deep Venous Thrombosis.

Heparin Use in Deep Venous Thrombosis

Heparin products used in the treatment of deep venous thrombosis (DVT) include unfractionated heparin and low molecular weight heparin (LMWH) The efficacy and safety of low-molecular-weight heparin (LMWH) for the initial treatment of DVT have been well established in several trials. Traditionally, heparin has been used only for admitted patients with DVT. Regular unfractionated heparin was the standard of care until the introduction of LMWH products. Heparin prevents extension of the thrombus and has been shown to significantly reduce (but not eliminate) the incidence of fatal and nonfatal pulmonary embolism and recurrent thrombosis.

Heparin is a heterogeneous mixture of polysaccharide fragments with varying molecular weights but with similar biological activity. The larger fragments exert their anticoagulant effect by interacting with antithrombin III (ATIII) to inhibit thrombin. ATIII, the body’s primary anticoagulant, inactivates thrombin and inhibits the activity of activated factor X in the coagulation process. The low-molecular-weight fragments exert their anticoagulant effect by inhibiting the activity of activated factor X. The hemorrhagic complications attributed to heparin are thought to arise from the larger higher-molecular-weight fragments. LMWH is prepared by selectively treating unfractionated heparin to isolate the low-molecular-weight (< 9000 Da) fragments.

Patients with recurrent venous thromboembolism (VTE) while on treatment with a non-LMWH anticoagulant should be switched to LMWH therapy.^[113]Those who suffer recurrent VTE while on LMWH therapy should receive an increased dose of LMWH.^[113]

For more information, see Heparin Use in Deep Venous Thrombosis.

Fondaparinux

Fondaparinux, a direct selective inhibitor of factor Xa, overcomes many of the aforementioned disadvantages of low-molecular-weight heparins (LMWHs). Pharmacokinetic studies of fondaparinux reveal that only a single-daily subcutaneous dose is required. Furthermore, a single dose of 7.5 mg is effective over a wide range of patient weights between 50 and 100 kg. Daily doses of 5 mg or 10 mg are appropriate for patients who weigh less or more than that weight range. Heparin-induced thrombocytopenia (HIT) has not been reported. Therapeutic monitoring of laboratory parameters such as the prothrombin time or activated partial thromboplastin time (aPTT) is also not required. In some regions, the cost of therapy with fondaparinux is less than enoxaparin when it is being used to bridge therapy to a vitamin K antagonist (VKA).

The combination of two factor Xa inhibitors may be an effective treatment strategy for acute venous thromboembolism (VTE).^[117] In an observational study, 80 of 87 consecutive Japanese patients with VTE who received SC fondaparinux for 7-10 days and then were switched to oral rivaroxaban for 7-14 days had treatment success. Both D-dimer levels and quantitative ultrasound thrombosis (QUT) scores were improved with the use of fondaparinux, and further reductions were achieved using rivaroxaban.^[117]

Buller and his coauthors on behalf of the Matisse Investigators conducted a randomized, double-blind, international study of fondaparinux versus enoxaparin on 2,205 patients with objectively confirmed acute deep venous thrombosis (DVT) and found the two agents to be comparable in safety and efficacy.^[6]Patients were randomly assigned to receive fondaparinux or enoxaparin therapy. Fondaparinux was administered as a single 7.5-mg subcutaneous daily dose, with adjustments made for those patients weighing less than 50 kg (5 mg) or greater than 100 kg (10 mg). Enoxaparin was given 1 mg/kg subcutaneously twice daily. Both agents were bridged with a VKA until a therapeutic international normalized ratio (INR) was achieved. Anticoagulation with a VKA was continued for 3 months. Efficacy was measured by the rate of recurrent VTE in the 3-month follow-up period after enrollment. Safety was assessed by the incidence of major bleeding and mortality over the same interval.^[6]

The recurrence rate showed a nonsignificant trend in favor of fondaparinux (3.9%) compared with enoxaparin (4.1%) (absolute difference = 0.15%; 95% CI, 1.8% to -1.5%).^[6]The conservative noninferiority margin was attained, and fondaparinux was determined to be equally as effective as enoxaparin for the treatment of DVT. Major bleeding rates were essentially identical, and mortality rates were also comparable. In a subgroup analysis, the authors also evaluated the relationship between the recurrence rate, the bleeding risks, and the patients’ body weight. In general, the safety and efficacy of fondaparinux were independent of body weight. However, patients with mild renal insufficiency and a low creatinine clearance had the same risk of bleeding in both the LMWH and fondaparinux groups. Overall, the authors concluded that once-daily fondaparinux was as effective and as safe as twice-daily, weight-adjusted enoxaparin.^[6]

The Matisse DVT trial confirmed that fondaparinux and enoxaparin have similar safety and efficacy for the initial treatment of DVT. Only one fixed-dosage regimen for fondaparinux is required for patients who weigh between 50 kg and 100 kg, and only one subcutaneous dose per day is required. This greatly simplifies the treatment of DVT and facilitates outpatient therapy. In the original study, about one third of the patients were treated partially or entirely as outpatients without any increased risk when compared with those treated as inpatients.

In renal insufficiency with a creatinine clearance less than 30 mL/min, major bleeding occurred in 2 of 25 patients (8%) on fondaparinux versus 1 of 18 patients (5.6%) treated with enoxaparin (P = NS). Because of the small sample size and the higher risk of bleeding, fondaparinux is contraindicated in patients with renal insufficiency and a creatinine clearance less than 30 mL/min.

In the event of a major bleed, protamine sulfate partially reverses the anticoagulant effect of enoxaparin. However, no specific antidote to fondaparinux is available. A recent study revealed that a bolus dose of 90 mcg/kg of recombinant factor VIIa reversed the anticoagulant effect of fondaparinux, at least in healthy volunteers given a larger 10-mg dose.^[118]

Rivaroxaban

Rivaroxaban (Xarelto) is an oral factor Xa inhibitor approved by the FDA in November 2012 for treatment of DVT or pulmonary embolism (PE) and for reduction of the risk of recurrent DVT and PE after initial treatment.^{[7, 8, 9]} Approval for this indication was based on studies totaling 9478 patients with DVT or PE. Participants were randomly assigned to receive rivaroxaban, a combination of enoxaparin and a VKA (eg, warfarin), or a placebo. Study endpoints were designed to measure the number of patients who experienced recurrent symptoms of DVT, PE, or death after receiving treatment.

Data from a pooled analysis of the EINSTEIN-DVT^[7]and EINSTEIN-PE^[8]trials suggested that rivaroxaban is as effective in preventing VTE recurrence as enoxaparin followed by a VKA and may be associated with less bleeding^[9]; in addition, the data suggested that there are no grounds for avoiding rivaroxaban use in high-risk groups (eg, fragile patients, cancer patients, and patients with a large clot).

Approximately 2.1% of patients treated with rivaroxaban experienced recurrent DVT or PE, compared with 1.8-3% treated with the enoxaparin and VKA combination.^{[7, 8]}

Additionally, results from extended treatment demonstrated a reduced risk of recurrent DVT and PE. Approximately 1.3% in the rivaroxaban group experienced recurrent DVT or PE, compared with 7.1% in the placebo group.^{[119, 120]}

Apixaban

In March 2014, the FDA approved apixaban (Eliquis) for the additional indication of prophylaxis of DVT and PE in adults who have undergone hip- or knee-replacement surgery. Support for this new indication was a result of the ADVANCE 1, 2, and 3 clinical trials that enrolled nearly 12,000 patients.^{[121, 122, 123]}Apixaban was originally approved by the FDA in December 2012 for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

In August 2014, apixaban was approved for treatment of DVT and PE.^[124]The approval for treatment of PE and prevention of recurrence was based on the outcome of the AMPLIFY (Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy) and AMPLIFY-EXT (extended treatment) studies, in which apixaban therapy was compared with enoxaparin and warfarin treatment. The AMPLIFY study showed that, in comparison with the standard anticoagulant regimen, apixaban therapy resulted in a 16% reduction in the risk of a composite endpoint that included recurrent symptomatic venous thromboembolism (VTE) or VTE-associated death.^{[125, 126]}

Data from the AMPLIFY-EXT trial showed that extended anticoagulation (12 months) with apixaban shortened hospital stays, reduced symptomatic recurrent venous thromboembolism or all-cause death without an associated increase in major episodes of hemorrhage when compared with placebo.^[127]

Dabigatran

Dabigatran (Pradaxa) inhibits free and clot-bound thrombin and thrombin-induced platelet aggregation. This agent was FDA approved in 2010 to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In April 2014, it was approved for the treatment of DVT and PE in patients who have been treated with a parenteral anticoagulant for 5-10 days. Additionally, it was approved to reduce the risk of DVT and PE recurrence in patients who have been previously treated. Approval was based on results from 4 global phase III trials that showed dabigatran was noninferior to warfarin and had a lower risk of major or clinically relevant bleeding compared with warfarin.^{[128, 129, 130]}There have been reports of severe and fatal bleeding in users of the drug.

The RE-COVER and RE-COVER II trials included patients with DVT and PE who were treated with parenteral anticoagulant therapy for 5-10 days. Results showed dabigatran was noninferior to warfarin in reducing DVT and PE after a median of 174 days of treatment with a lower risk of bleeding compared with warfarin.^{[128, 129]}

The RE-SONATE trial and RE-MEDY trials included patients (n=2856) with acute DVT and PE who had completed at least 3 months of anticoagulant therapy. Results from this trial showed dabigatran was noninferior to warfarin in the extended treatment of VTE and carried a lower risk of major or clinically relevant bleeding than warfarin.^[130]

Edoxaban

Edoxaban (Savaysa) was approved by the FDA in January 2015 for the treatment of DVT and PE in patients who have been initially treated with a parenteral anticoagulant for 5-10 days.^[131]Approval was based on the Hokusai-VTE study that included 4,921 patients with DVT and 3,319 patients with PE.^{[131, 132]}

Among patients with PE, 938 had right ventricular dysfunction, as assessed by measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels.^[132]There was a 3.3% rate of recurrent VTE in this subgroup in those who received edoxaban compared to 6.2% in the group that received warfarin. The investigators concluded that edoxaban was not only noninferior to high-quality standard warfarin therapy but also caused significantly less bleeding in a broad spectrum of patients with VTE, including those with severe PE.^[132]

Betrixaban

Betrixaban (Bevyxxa), a FXa inhibitor, was approved by the FDA in June 2017.^[133]It is indicated for the prophylaxis of VTE in adults hospitalized for acute medical illness who are at risk for thromboembolic complications owing to moderate or severe restricted mobility and other risk factors that may cause VTE.^[133]

Approval of betrixaban was based on data from the phase 3 APEX studies.^{[134, 135]}These randomized, double-blind, multinational clinical trials compared extended-duration betrixaban (35-42 days) to short-duration enoxaparin (6-14 days) for VTE in 7,513 acutely medically ill hospitalized patients with VTE risk factors.^{[133, 134, 135]}Patients in the betrixaban group received an initial dose of 160 mg orally on day 1, followed by 80 mg once daily for 35-42 days, and received a placebo injection once daily for 6-14 days. Patients in the enoxaparin group received 40 mg subcutaneously once daily for 6-14 days and took an oral placebo once daily for 35-42 days.^{[133, 134, 135]}

Efficacy was measured in 7,441 patients using a composite outcome score composed of the occurrence of asymptomatic or symptomatic proximal DVT, nonfatal PE, stroke, or VTE-related death.^{[133, 134, 135]} Those who received betrixaban showed significant decreases in VTE events (4.4%) compared with patients in the enoxaparin group (6%).

Duration of Anticoagulation

For the first episode of deep venous thrombosis (DVT), patients should be treated for 3-6 months. Recurrent episodes should be treated for at least 1 year.

The American College of Chest Physicians (ACCP) recommends cessation of anticoagulant therapy after 3 months of treatment in those with (1) surgery-associated acute proximal DVT, (2) an acute proximal DVT or PE provoked by a nonsurgical transient risk factor, and (3) a first unprovoked VTE and a high risk of bleeding.^[113](In those with a low or moderate bleeding risk, extend anticoagulation without a scheduled stop date.)^[113]

Prandoni et al found that the use of ultrasonography to determine the duration of anticoagulation can reduce recurrences of venous thromboembolism after a first episode of acute proximal DVT. In the study, 538 consecutive outpatients who had completed an uneventful 3-month period of anticoagulation were randomized to receive either fixed-duration anticoagulation (< 9 months for secondary DVT and up to 21 months for unprovoked thrombosis) or flexible-duration anticoagulation, with treatment discontinued once ultrasound showed recanalization of the affected veins. Recurrent venous thromboembolism developed in 17.2% of the patients allocated to fixed-duration anticoagulation and 11.9% of the patients allocated to flexible-duration anticoagulation; no significant difference was noted in the rate of major bleeding.^[136]

Patients with cancer have a particularly higher rate of DVT recurrence than noncancer patients. Long-term therapy for DVT is strongly recommended. Studies have shown a lower rate of venous thromboembolism (VTE) recurrence without increasing the risk of bleeding with low-molecular-weight heparin (LMWH) therapy. Reports also describe that the LMWH compounds may decrease the all-cause mortality rate. The author recommends LMWH therapy alone without crossover to warfarin if the patient’s insurance covers it.

Indefinite therapy is recommended for patients with recurrent episodes of venous thrombosis regardless of the cause. The risk of recurrent thromboembolism during a 4-year follow-up period was reduced from 21% to 3% with continued anticoagulation. However, the incidence of major bleeding increased from 3% to 9%.^[137]

Long-term therapy with LMWH has been shown to be as effective as warfarin in the treatment of venous thrombosis, except in those patients with a concurrent malignancy. In this subgroup, LMWH was shown to be more effective than oral therapy.^{[138, 139]}Initial studies have also shown LMWH to be effective in pregnant patients, but long-term, large randomized trials have yet to be completed.^[140]

Complications of Anticoagulant Therapy

Hemorrhagic complications are the most common adverse effects of anticoagulant therapy. Anticoagulation therapy for 3-6 months results in major bleeding complications in 3-10% of patients.^[141]High-risk populations (>65 y with a history of stroke, gastrointestinal [GI] bleed, renal insufficiency, or diabetes) have a 5-23% risk of having major hemorrhage at 90 days. Patients who require yearlong or indefinite anticoagulation (because of chronic risk factors) have double the risk of hemorrhage. Significant bleeding (ie, hematemesis, hematuria, GI hemorrhage) should be thoroughly investigated because anticoagulant therapy may unmask a preexisting disease (eg, cancer, peptic ulcer disease, arteriovenous malformation).

The treatment of hemorrhage while taking heparin depends on the severity of the bleeding and the extent to which the activated partial thromboplastin time (aPTT) is elevated above the therapeutic range. Patients who hemorrhage while receiving heparin are best treated by discontinuing the drug. The half-life is relatively short, and the aPTT usually returns to the reference range within a few hours. Treatment with fresh frozen plasma or platelet infusions is ineffective. For severe hemorrhage, such as intracranial or massive gastrointestinal bleeding, heparin may be neutralized by protamine at a dose of 1 mg for every 100 units. Protamine should be administered at the same time that the infusion is stopped.

The treatment of major hemorrhage associated with low-molecular-weight heparin (LMWH) is similar to heparin. However, the half-life of these agents is longer (4-6 h). As with heparin, fresh frozen plasma or platelet transfusions are ineffective. Protamine may be used, but it only reverses 60% of the drug’s effects.

The risk of bleeding on warfarin is not linearly related to the elevation of the international normalized ratio (INR). The risk is conditioned by other factors, including poor follow-up, drug interactions, age, and preexisting disorders that predispose to bleeding.

Patients who hemorrhage while receiving oral warfarin are treated by withholding the drug and administering vitamin K. Severe life-threatening hemorrhage is managed with fresh frozen plasma in addition to vitamin K. Recombinant factor VIIa is another option especially for central nervous system hemorrhage.

Additional complications include the following:

Systemic embolism
Chronic venous insufficiency
Postthrombotic syndrome (ie, pain and edema in the affected limb without new clot formation)
Soft tissue ischemia associated with massive clot and very high venous pressures - phlegmasia cerulea dolens

Emerging Anticoagulant Agents

The qualities desired in the ideal anticoagulant are ease of administration, efficacy and safety (with minimal complications or adverse effects), rapid onset, a therapeutic half-life, and minimal or no monitoring. Predictable and reversible action, with few drug or dietary interactions, and cost also are important. Achieving all these criteria in a single agent has not yet been achieved. Each of the anticoagulant agents available today has generally been able to incorporate some, but not all, of these characteristics.

In patients with deep venous thrombosis (DVT), anticoagulation remains the cornerstone of treatment. The relatively recent development of novel oral anticoagulants has provided clinicians with an expanding set of options for DVT treatment.^[142]

Current research in anticoagulants involves investigations into drugs that act on various phases of the coagulation cascade. Drugs under investigation that act in the initiation phase include tissue factor pathway inhibitors (TFPIs) and nematode anticoagulant peptide (NAPc2). Drugs that act on the third stage of the coagulation cascade, the thrombin activity phase, include the direct thrombin inhibitors. A partial listing of these emerging new anticoagulants includes razaxaban, idraparinux, bivalirudin, lepirudin, and ximelagatran.

For more information, see Emerging Anticoagulant Agents in Deep Venous Thrombosis.

Reversal of Anticoagulation

Anticoagulation-related major bleeding is associated with an increased risk of death and thrombotic events, independent of the class of anticoagulant used. Although older agents of anticoagulation and their reversal are well studied, the newer agents lack similar antidotes. With the increasing use of non–vitamin K antagonist oral anticoagulants (NOAC), the number of patients who require reversal of their anticoagulant effects can be expected to rise. The following section describes the reversal agents for both older and new anticoagulants.

Heparin

Heparin has a relatively short half-life of about 60–90 minutes and, therefore, the anticoagulant effect of therapeutic doses of heparin will mostly be eliminated at 3-4 hours after termination of continuous intravenous administration.

For a more immediate neutralization of heparin, protamine sulfate can be administered at a dose of 1 mg for every 100 units of heparin. Protamine was originally isolated from fish sperm and binds to heparin to form a stable, biologically inactive complex.^{[143, 144]}

Lower molecular weight heparins

Currently, there are no specific antidotes to low molecular weight heparins. Recombinant FVIIa (rVIIA) has been shown to stop bleeding in patients anticoagulated with fondaparinux; however, no randomized controlled trials on such patients have been conducted.

Warfarin

Vitamin K

In patients with clinically significant bleeding, vitamin K can be used to reverse the anticoagulant effect of vitamin K antagonists (VKA). Vitamin K can be given orally or intravenously. The parenteral route has a more rapid onset; however, it is associated with a slightly increased risk of allergic reaction.

Fresh frozen plasma (FFP)

In case of a life-threatening emergency, FFP can be used for the reversal of VKA. FFP contains all the coagulation factors in normal concentrations. However, FFP should be used with caution, as it has the potential to cause volume overload, allergic reaction, and transfusion-related reactions (eg, transfusion-related acute lung injury).^[145]

Prothrombin complex concentrates (PCCs)

In the case of serious and life-threatening bleeding, immediate correction of the international normalized ratio (INR) can be achieved by the administration of PCCs. These contain 3 or 4 of the vitamin K–dependent coagulation factors, as well as proteins C and S. In a prospective study, administration of PCCs has been shown to result in sustained hemostasis in patients using VKA.

Non–vitamin K antagonist oral anticoagulants (NOACs)

The new oral anticoagulant factor Xa or IIa inhibitors have numerous advantages over traditional VKAs, including rapid therapeutic effectiveness, ease of dosing, and lack of monitoring. Until recently, there were no approved drug-specific reversal agents for the NOACs. A number of drugs are currently under development.^{[146, 147]}

Due to the short half-life of FXa inhibitors, discontinuation of the drugs suffice in clinical situations in which there is time to await spontaneous clearance.

Currently, PCCs can be used to address severe bleeding in patients taking NOACs when administered in high enough dosages. Some guidelines suggest an initial dose of 25 to 50 U/kg of PCCs in life-threatening emergencies, to be repeated if necessary.

Idarucizumab (Praxbind)

Idarucizumab is a humanized antibody fragment directed against dabigatran. This agent has been shown to completely reverse the anticoagulant effect of dabigatran within minutes; on October 16, 2015, it was approved by the FDA as an antidote for dabigatran.^{[148, 149, 150, 151]}

Andexanet alfa

Andexanet alfa is a recombinant, modified FXa molecule that acts as a decoy protein that is catalytically inactive but has a high affinity for FXa inhibitors. It is being developed as an antidote for apixaban, edoxaban, and rivaroxaban. Andexanet alfa has been shown to reverse the anticoagulant effects of apixaban and rivaroxaban in human volunteers, and more studies are ongoing.^[152]

Aripazine (PER977, ciraparantag)

Aripazine is a synthetic small molecule that has broad activity against both old (heparin, low molecular weight heparin) and new oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban). A 2014 study of human volunteers demonstrated that administration of aripazine reversed the prolonged clotting time caused by edoxaban. Further human trials are ongoing.^[153]

Pharmacologic Thrombolysis

Use of thrombolytic medications to lyse deep venous thrombosis can cause intracranial bleeding, though this is infrequent, and death or impairment can result. Accordingly, careful assessment of the indications for lysis against the possibility of bleeding must be carried out before pharmacologic thrombolysis is attempted.

The need should be compelling when thrombolysis is considered in a setting of known contraindications. Factors such as recent surgery, stroke, gastrointestinal or other bleeding, and underlying coagulopathy increase the bleeding risk when the thrombolytic medication is administered. The process of obtaining informed consent should include a discussion of these risks.

General Principles of Endovascular Intervention

Percutaneous transcatheter treatment of patients with deep venous thrombosis (DVT) consists of thrombus removal with catheter-directed thrombolysis, mechanical thrombectomy, angioplasty, and/or stenting of venous obstructions. Consensus has been reached regarding indications for the procedure, although it is based on midlevel evidence from nonrandomized controlled trials. The goals of endovascular therapy include reducing the severity and duration of lower-extremity symptoms, preventing pulmonary embolism, diminishing the risk of recurrent venous thrombosis, and preventing postthrombotic syndrome. A randomized controlled trial comparing catheter-directed thrombolysis to conventional anticoagulation demonstrated a lower incidence of postthrombotic syndrome and improved iliofemoral patency in patients with a high proximal DVT and low risk of bleeding.^[154]

Indications for intervention include the relatively rare phlegmasia or symptomatic inferior vena cava thrombosis that responds poorly to anticoagulation alone, or symptomatic iliofemoral or femoropopliteal DVT in patients with a low risk of bleeding. Contraindications are the same as those for thrombolysis in general. Absolute contraindications include active internal bleeding or disseminated intravascular coagulation, a cerebrovascular event, trauma, or neurosurgery within 3 months. Unfortunately, most patients with DVT have absolute contraindications to thrombolytic therapy. The American College of Chest Physicians (ACCP) consensus guidelines recommend thrombolytic therapy only for patients with massive ileofemoral vein thrombosis associated with limb ischemia or vascular compromise.^{[113, 155]}

For more information, see Inferior Vena Caval Thrombosis.

Percutaneous mechanical thrombectomy devices are a popular adjunct to catheter-directed thrombolysis. Although these devices may not completely remove thrombus, they are effective for debulking and for minimizing the dose and time required for infusing a thrombolytic. Percutaneous mechanical thrombectomy has developed as an attempt to shorten treatment time and avoid costly ICU stays during thrombolytic infusion. The most basic mechanical method for thrombectomy is thromboaspiration, or the aspiration of thrombus through a sheath. Mechanical disruption of venous thrombosis has the potential disadvantage of damaging venous endothelium and valves, in addition to thrombus fragmentation and possible pulmonary embolism.

For more information, see Percutaneous Transcatheter Treatment of Deep Venous Thrombosis.

Surgical Thrombectomy

Surgical thrombus removal has traditionally been used in patients with massive swelling and phlegmasia cerulea dolens. In many patients, fibrinolysis alone is highly effective, and it has become the primary treatment of choice for many forms of venous and arterial thrombosis. Unfortunately, when thrombosis is extensive, fibrinolysis alone may be inadequate to dissolve the volume of thrombus present. Even when the bulk of the thrombus is not excessive, many patients with thrombosis are poor candidates for fibrinolysis because of recent surgery or trauma involving the central nervous system or other noncompressible areas.

Precisely defining the location and extent of thrombosis before considering any surgical approach to the problem is important. Duplex ultrasonography may sometimes be sufficient for this purpose, but venography (including routine contralateral iliocavography) is a more reliable guide to the anatomy and the particular pathology that must be addressed.

The patient must be heparinized before the procedure. Traditional venous thrombectomy is performed by surgically exposing the common femoral vein and saphenofemoral junction through a longitudinal skin incision. A Fogarty catheter is passed through the clot, and the balloon is inflated and withdrawn, along with the clot. However, care must be taken to avoid dislodging the clot or breaking it into small fragments because pulmonary embolus will result.

A proximal balloon or a temporary caval filter may be used to reduce the likelihood of embolization. Venography is mandatory to confirm the clearance of the thrombus. Back bleeding does not indicate clot clearance because a patent valve can block flow, or flow can be present with patent tributaries.

Venous valves may sometimes prevent the passage of a catheter in a retrograde direction down the leg. When this happens, the leg may be wrapped tightly with an Esmarch bandage in an attempt to force clot extrusion. After the thrombus has been removed, construction of a small arteriovenous fistula may assist in maintaining patency by increasing the flow velocity through a thrombogenic iliofemoral venous segment and promoting collateral development. The fistula is usually performed between the saphenous vein and the femoral vein. To reduce the likelihood of rethrombosis, heparin anticoagulation is usually initiated before surgery, continued during the procedure, and maintained for 6-12 months afterward. Leg compression devices are useful to maintain venous flow.

Outcomes from multiple studies have shown rethrombosis rates around 12% when a temporary arteriovenous fistula is used. Optimal results were found in thrombosis less than 7 days, clearance of thrombus from the external and internal iliac veins, intraoperative venography, early ambulation, and religious use of compression stockings. In a prospective randomized study from Sweden comparing surgery with anticoagulation, at 5 years, 37% of operated patients were asymptomatic, compared with just 18% in the anticoagulation group. Vein patency was 77% in the surgical group compared with just 30% in the anticoagulation group.^[156]

Table. Surgical Thrombectomy with Temporary Arteriovenous Fistula in Early Iliac Vein Patency^[157] (Open Table in a new window)

Study and Number of Patients	Patent Iliac Vein
Delin (13)	85%
Plate (31)	87%
Piquet (92)	80%
Einarsson (51)	88%
Juhan (42)	93%
Vollmar (93)	82%
Kniemeyer (185)	96%
Neglen (48)	89%

Total (555)	88%

Placement of Inferior Vena Cava Filters

Inferior vena cava filters are not recommended in patients with acute venous thromboembolism (VTE) on anticoagulant therapy.^[113] These filters were developed in an attempt to trap emboli and minimize venous stasis. In most patients with deep venous thrombosis (DVT), prophylaxis against the potentially fatal passage of thrombus from the lower extremity or pelvic vein to the pulmonary circulation is adequately accomplished with anticoagulation. An inferior vena cava filter is a mechanical barrier to the flow of emboli larger than 4 mm.

In the past, inferior vena cava filters were placed in 4.4% of patients. Recent use was documented in 14% of patients with DVT; this rate was perhaps due to broadened indications with the introduction of removable filters. Temporary or removable filters, all of which may also be left as permanent, permit transient mechanical pulmonary embolism (PE) prophylaxis. This option may be useful in the setting of polytrauma, head injury, hemorrhagic stroke, known VTE, or major surgery when PE prophylaxis must be maintained during a short-term contraindication to anticoagulation.

In a randomized trial, the addition of an inferior vena cava filter to anticoagulation for DVT increased the risk of recurrent DVT (11.6% to 20.8%) and did not improve the 2-year survival rate. However, the filter group had significantly fewer PEs (1.1% vs 4.8%). Of note was the risk of major bleeding at 3 months (10.5%). This result agrees with other reports and highlights the usual trade-off of prophylaxis with a filter versus anticoagulation and the respective complication risks of new DVT (peripheral to the filter) versus major hemorrhage. In the elderly patient with an increased risk of bleeding, and particularly if the patient is at risk for trauma, the risk and benefits may favor use of a filter.

Catheter-directed thrombolysis does not add to the risk of PE to warrant routine filter placement. However, for patients with contraindications to pharmacologic lysis in whom a percutaneous mechanical thrombectomy device is to be used, a filter may be a useful adjunct.^[158]

The ideal vena cava filter would trap venous emboli while maintaining normal venous flow. Many different filter configurations have been used, but the current benchmark remains the Greenfield filter with the longest long-term data. Patency rates greater than 95% and recurrent embolism rates of less than 5% have been demonstrated by numerous studies. The conical shape allows central filling of emboli while allowing blood on the periphery to flow freely. Numerous other filters with similar track records have since been developed, including filters that can be removed.

Regardless of the type of filter placed, the technique remains the same. Local anesthetic is used to anesthetize either the groin for a femoral vein approach or the neck for a jugular vein approach. A single wall needle is used under ultrasonic guidance to enter the target vein, and a 0.035-inch guidewire is passed into the inferior vena cava. A venogram is performed to identify the renal veins and measure the diameter of the vena cava to ensure the cava is not too big for the filter. Intravascular ultrasound (IVUS) can also be used for this purpose. It has the added benefit of not only allowing for bedside filter placement in sick intensive care unit (ICU) patients, but it also obviates the need for IV contrast. The correct filter location traditionally entails an infra-renal fixation with central filter extension to the level of the renal veins. Placement in the suprarenal inferior vena cava or superior vena cava may be indicated in some situations.

American Heart Association recommendations for inferior vena cava filters include the following^[10]:

Confirmed acute proximal DVT or acute PE in patient with contraindication for anticoagulation (this remains the most common indication for inferior vena cava filter placement)
Recurrent thromboembolism while on anticoagulation
Active bleeding complications requiring termination of anticoagulation therapy

Relative contraindications include the following:

Large, free-floating iliofemoral thrombus in high-risk patients
Propagating iliofemoral thrombus while on anticoagulation
Chronic PE in patient with pulmonary hypertension and cor pulmonale
Patient with significant fall risk

For more information, see Inferior Vena Caval Thrombosis and Inferior Vena Cava Filters.

Replacement of Venous Valves

Percutaneously placed bioprosthetic venous valves are under development and may provide a minimally invasive therapy to the long-term complication of postthrombotic syndrome due to valve destruction. If successful, this approach may provide a percutaneous therapeutic alternative for patients with primarily palliative options to manage their venous reflux symptoms. An effective therapy should diminish one of the primary indications for aggressive thrombolytic therapy for acute deep venous thrombosis.

Use of Elastic Compression Stockings

Postthrombotic syndrome (PTS) affects approximately 50% of patients with deep venous thrombosis (DVT) after 2 years. Elderly patients and patients with recurrent ipsilateral DVT have the highest risk. Below-the-knee elastic compression stockings (ECS) assist the calf muscle pump and reduce venous hypertension and venous valvular reflux. This reduces leg edema, aids the microcirculation, and prevents venous ischemia.

In a randomized controlled study from an Italian university setting involving 180 patients who presented with a first episode of symptomatic proximal DVT, Prandoni and colleagues found below-the-knee ECS to have value for the prevention of PTS. After conventional anticoagulation with heparin, patients were discharged on therapeutic warfarin for 3-6 months and randomly assigned to the control group (no ECS) or the ECS group. Graduated compression stockings with ankle pressures of 30-40 mm Hg were given to the participants, who were required to wear them daily on the affected leg or legs over 2 years. Ninety percent of trial participants were compliant (wore the stockings for at least 80% of daytime hours), and 5-year cumulative data was evaluated to compare the incidence of PTS between the groups.^[159]

A standardized validated scale was used to assess symptoms, severity, and/or progression of PTS. PTS occurred in 26% of patients who wore ECS compared with 49% of patients without ECS. All patients with PTS except one developed manifestations of the syndrome within the first 2 years after the initial diagnosis of DVT. The number of patients who need to be treated with ECS was estimated at 4.3 to prevent one case of PTS. The adjusted hazard ratio was 0.49 (CI 0.29-0.84, P = .011) in favor of ECS. Almost 50% of their patients with proximal DVT developed PTS within 2 years.

The regular use of graduated elastic compression stockings reduced the incidence of PTS by 50%. The authors also noted that the benefit conferred by ECS was not related to the rate of recurrent DVT, which was identical in both groups. The authors strongly recommended the early use and widespread implementation of graduated elastic stockings with adequate anticoagulant therapy for symptomatic proximal DVT to prevent the development of PTS.

The Eighth ACCP Conference on Antithrombotic and Thrombolytic Therapy observed that PTS occurs in 20-50% of patients with objectively confirmed DVT and assigned a grade 1A recommendation for the use of graduated elastic compression stockings for 2 years after the onset of proximal DVT.^{[144, 160]}With the adoption of outpatient therapy for proximal DVT, the initial management of DVT increasingly becomes the responsibility of the emergency physician.

More recently, the ACCP recommends against the routine use of compression stockings in patients with acute DVT to prevent postthrombotic syndrome.^[113]

Ambulation

Controversy exists regarding the role of ambulation in the therapy of deep venous thrombosis (DVT). A study by Partsch reviewed the myths surrounding immediate ambulation and compression in the patient with newly diagnosed DVT and concluded that early ambulation and compression is not associated with any significant risk of pulmonary embolism (PE).^[161]It is well recognized from the older literature that almost 50% of patients with acute proximal DVT have evidence, based on V/Q pulmonary scanning, of asymptomatic PE at baseline. Analyzing the effect of ambulation and compression in this patient cohort focused on the development of a new PE, the relief of pain and swelling, and the reduction in the incidence and severity of postthrombotic syndrome (PTS).

The authors cited 2 small previous studies that demonstrated that the incidence of a new PE after initiation of anticoagulant therapy with a low-molecular-weight heparin (LMWH) did not increase significantly in patients treated with early ambulation and compression. They had previously reported their own prospective cohort study of 1289 patients with acute DVT treated as outpatients with LMWH, early ambulation, and compression. Partsch et al reported that only 77 of 1289 patients (5.9%) developed a new PE, only 6 of 1289 patients (0.4%) of these were symptomatic, and only 3 deaths (0.23%) were attributed to the PE. This was not significantly different than historical controls.

A systematic review by Kahn et al found that in patients with acute DVT, early walking exercise is safe and may help to reduce acute symptoms and that in patients with previous DVT, exercise training does not increase leg symptoms acutely and may help to prevent or improve the postthrombotic syndrome.^[162]

In Europe, early ambulation and compression has been the mainstay of adjunctive treatment for DVT. In North America, the unsubstantiated fear of dislodging clots by ambulation led clinicians to recommend bed rest and leg elevation to their patients. The authors explained that bed rest promotes venous stasis, which is a major risk factor for DVT and, therefore, may actually enhance thrombus propagation and the risk of subsequent PE.

The authors also cited a number of other studies that revealed a significant decrease in leg swelling (using leg circumference measures) and pain (analog pain scales and quality of life scores) with early ambulation and compression. They also recognized the limited data that are available to assess the effect of early ambulation and compression on the subsequent development of PTS. In their own small trial, they reported a trend toward a lower incidence of PTS. They conceded that a larger, long-term study would be required. Nevertheless, they strongly recommended early ambulation for their patients in addition to elastic compression stockings.

The ACCP Consensus Conference on Antithrombotic and Thrombolytic Therapy for venous thromboembolism also recommended ambulation as tolerated for patients with DVT.^{[144, 160]}Therefore, early ambulation on day 2 after initiation of outpatient anticoagulant therapy in addition to effective compression is strongly recommended. Early ambulation without ECS is not recommended. The fear of dislodging clots and precipitating a fatal PE is unfounded.

Treatment of Superficial Thrombophlebitis

Superficial thrombophlebitis is often associated with deep venous thrombosis (DVT) in two specific settings. The following high-risk groups require further evaluation for DVT:

Superficial thrombophlebitis in the absence of coexisting venous varices and no other obvious etiology
Involvement of the greater saphenous vein above the knee, especially if it extends to the saphenofemoral junction (These latter patients should be treated as having proximal vein DVT and treated with full anticoagulant therapy.)

Uncomplicated superficial thrombophlebitis may be treated symptomatically with heat, nonsteroidal anti-inflammatory agents (NSAIDs), and compression hose. Bed rest is not recommended.

Some centers recommend full anticoagulation for high-risk patients with isolated superficial thrombophlebitis. Some physicians may anticoagulate high-risk patients with negative initial study results until follow-up surveillance studies are completed. An alternative approach involves symptomatic care alone with close follow-up and repeated noninvasive testing in 1 week. Full anticoagulation is then reserved only for those patients with proven proximal vein DVT.

Treatment of Axillary and Subclavian Vein Thrombosis

This was first described by Paget in 1875 and von Schrötter in 1884 and is sometimes referred to as Paget–von Schrötter syndrome. The pathophysiology is similar to that of deep venous thrombosis (DVT), and the etiologies overlap. The incidence is lower than that of lower extremity DVT because of decreased hydrostatic pressure, fewer venous valves, higher rates of blood flow, and less frequent immobility of the upper arm.

Thoracic outlet compression from cervical ribs or congenital webs may precipitate axillary/subclavian venous thrombosis. Catheter-induced thrombosis is increasingly a common cause of this condition. The increased use of subclavian catheters for chemotherapy and parenteral nutrition has resulted in a dramatic increased incidence of proven thrombosis. Similarly, pulmonary artery catheters are associated with a high incidence of internal jugular and subclavian vein thrombosis. Pulmonary embolism (PE) occurs in approximately 10% of patients. Fatal or massive PE is extremely rare.

Ultrasonography and venography are the diagnostic tests of choice. Ultrasonographic findings may be falsely negative because of collateral blood flow. Duplex ultrasonography is accurate for the evaluation of the internal jugular vein and its junction with the subclavian vein where the innominate vein begins.

Thrombolytic therapy is the treatment of choice for axillary/subclavian venous thrombosis. Restoration of venous patency is more critical for the prevention of chronic venous insufficiency in the upper extremity. Thrombolysis is best accomplished with local administration of the thrombolytic agent directly at the thrombus. After completion of a venographic study, a catheter is floated up to the site of the clot, and the thrombolytic agent is administered as a direct infusion. Venographic assessment for clot lysis is repeated every 4-6 hours until venous patency is restored. Heparin is usually given concurrently to prevent rethrombosis.

In the presence of anatomic abnormalities, surgical therapy is recommended to minimize long-term morbidity and recurrence. Catheter-induced thrombosis may require removal of the device. Locally infused thrombolytic agents have been used successfully and are currently the treatment of choice.

Prophylaxis of Deep Venous Thrombosis

Prevention of deep venous thrombosis (DVT) has long been studied in various clinical situations with varying degrees of success. Primary prophylaxis is directed toward acting on one or more components of the Virchow triad, affecting blood flow, coagulation, or vessel wall endothelium. Methods of prophylaxis may be generally divided into mechanical and pharmacologic. Many pharmacologic agents are currently available to prevent thrombosis. Agents that retard or inhibit the process belong under the general heading of anticoagulants. Agents that prevent the growth or formation of thrombi are properly termed antithrombotics and include anticoagulants and antiplatelet drugs, whereas thrombolytic drugs lyse existing thrombi.

Surgical patients undergoing general anesthesia have been extensively studied. Studies of pneumatic compression in cardiac surgery and neurosurgical patients have shown a distinct improvement in the incidence of DVT without the added risk of bleeding.^{[163, 164]}However, the effect is less impressive in higher-risk patients, and compliance can be difficult. Routine use of anticoagulant prophylaxis after cardiac surgery is discouraged.^[165] Kolluri et al showed no benefit of prophylactic postoperative fondaparinux following after coronary artery bypass graft (CABG) surgery.^[165]

Timing and duration of prophylactic agents has also been determined to have a significant effect on the development of DVT. Early prophylaxis in surgical patients with low molecular weight heparin has been associated with significant reductions in postoperative venous thrombosis. If surgery is delayed, then prophylaxis with low-dose unfractionated heparin or low molecular weight heparin should be initiated at the time of admission and discontinued prior to surgery.

Major surgical and high-risk orthopedic procedures place patients at risk for deep venous thrombosis and venous thromboembolism, including pulmonary embolism. Complications of DVT include postphlebitic syndrome or death from pulmonary embolism. Therefore, prophylaxis with anticoagulant medications, as well as the adjunct use of mechanical devices, is essential. The most effective treatment protocol for a patient must be determined on a case-by-case basis and account for the risk-benefit ratio in each situation. A risk stratification protocol, such as that developed by the American College of Chest Physicians (ACCP), is recommended to determine the appropriate level and method of treatment.

For more information, see Deep Venous Thrombosis Prophylaxis.

Guidelines

Tapson VF. Acute pulmonary embolism. N Engl J Med. 2008 Mar 6. 358(10):1037-52. [QxMD MEDLINE Link].
Haeger K. Problems of acute deep venous thrombosis. I. The interpretation of signs and symptoms. Angiology. 1969 Apr. 20(4):219-23. [QxMD MEDLINE Link].
McLachlin J, Richards T, Paterson JC. An evaluation of clinical signs in the diagnosis of venous thrombosis. Arch Surg. 1962 Nov. 85:738-44. [QxMD MEDLINE Link].
Meignan M, Rosso J, Gauthier H, et al. Systematic lung scans reveal a high frequency of silent pulmonary embolism in patients with proximal deep venous thrombosis. Arch Intern Med. 2000 Jan 24. 160(2):159-64. [QxMD MEDLINE Link].
[Guideline] Snow V, Qaseem A, Barry P, et al. Management of venous thromboembolism: a clinical practice guideline from the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med. 2007 Feb 6. 146(3):204-10. [QxMD MEDLINE Link].
Buller HR, Ten Cate-Hoek AJ, Hoes AW, et al. Safely ruling out deep venous thrombosis in primary care. Ann Intern Med. 2009 Feb 17. 150(4):229-35. [QxMD MEDLINE Link].
Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23. 363(26):2499-510. [QxMD MEDLINE Link]. [Full Text].
Buller HR, Prins MH, Lensin AW, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5. 366(14):1287-97. [QxMD MEDLINE Link]. [Full Text].
Hughes S. Rivaroxaban stands up to standard anticoagulation for VTE treatment. Medscape Medical News. Medscape Heartwire from WebMD. December 13, 2012. Available at http://www.medscape.com/viewarticle/776147. Accessed: March 19, 2013.
Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011 Apr 26. 123(16):1788-830. [QxMD MEDLINE Link].
Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ 3rd. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med. 1998 Mar 23. 158(6):585-93. [QxMD MEDLINE Link].
Useche JN, de Castro AM, Galvis GE, Mantilla RA, Ariza A. Use of US in the evaluation of patients with symptoms of deep venous thrombosis of the lower extremities. Radiographics. 2008 Oct. 28(6):1785-97. [QxMD MEDLINE Link].
Chang R, Chen CC, Kam A, Mao E, Shawker TH, Horne MK 3rd. Deep vein thrombosis of lower extremity: direct intraclot injection of alteplase once daily with systemic anticoagulation--results of pilot study. Radiology. 2008 Feb. 246(2):619-29. [QxMD MEDLINE Link].
Biuckians A, Meier GH 3rd. Treatment of symptomatic lower extremity acute deep venous thrombosis: role of mechanical thrombectomy. Vascular. 2007 Sep-Oct. 15(5):297-303. [QxMD MEDLINE Link].
Li W, Salanitri J, Tutton S, et al. Lower extremity deep venous thrombosis: evaluation with ferumoxytol-enhanced MR imaging and dual-contrast mechanism--preliminary experience. Radiology. 2007 Mar. 242(3):873-81. [QxMD MEDLINE Link].
Kakkos SK, Caprini JA, Geroulakos G, Nicolaides AN, Stansby GP, Reddy DJ. Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism in high-risk patients. Cochrane Database Syst Rev. 2008 Oct 8. CD005258. [QxMD MEDLINE Link].
Araki CT, Back TL, Padberg FT, et al. The significance of calf muscle pump function in venous ulceration. J Vasc Surg. 1994 Dec. 20(6):872-7; discussion 878-9. [QxMD MEDLINE Link].
Wakefield TW, Strieter RM, Schaub R, et al. Venous thrombosis prophylaxis by inflammatory inhibition without anticoagulation therapy. J Vasc Surg. 2000 Feb. 31(2):309-24. [QxMD MEDLINE Link].
Wakefield TW, Proctor MC. Current status of pulmonary embolism and venous thrombosis prophylaxis. Semin Vasc Surg. 2000 Sep. 13(3):171-81. [QxMD MEDLINE Link].
Gibbs NM. Venous thrombosis of the lower limbs with particular reference to bed-rest. Br J Surg. 1957 Nov. 45(191):209-36. [QxMD MEDLINE Link].
Sevitt S. The structure and growth of valve-pocket thrombi in femoral veins. J Clin Pathol. 1974 Jul. 27(7):517-28. [QxMD MEDLINE Link]. [Full Text].
Aronson DL, Thomas DP. Experimental studies on venous thrombosis: effect of coagulants, procoagulants and vessel contusion. Thromb Haemost. 1985 Dec 17. 54(4):866-70. [QxMD MEDLINE Link].
Wessler S, Reimer SM, Sheps MC. Biologic assay of a thrombosis-inducing activity in human serum. J Appl Physiol. 1959 Nov. 14:943-6. [QxMD MEDLINE Link].
Sevitt S. The mechanisms of canalisation in deep vein thrombosis. J Pathol. 1973 Jun. 110(2):153-65. [QxMD MEDLINE Link].
Gandhi RH, Irizarry E, Nackman GB, Halpern VJ, Mulcare RJ, Tilson MD. Analysis of the connective tissue matrix and proteolytic activity of primary varicose veins. J Vasc Surg. 1993 Nov. 18(5):814-20. [QxMD MEDLINE Link].
Rizzi A, Quaglio D, Vasquez G, et al. Effects of vasoactive agents in healthy and diseased human saphenous veins. J Vasc Surg. 1998 Nov. 28(5):855-61. [QxMD MEDLINE Link].
Monreal M, Martorell A, Callejas JM, et al. Venographic assessment of deep vein thrombosis and risk of developing post-thrombotic syndrome: a prospective study. J Intern Med. 1993 Mar. 233(3):233-8. [QxMD MEDLINE Link].
Strandness DE Jr, Langlois Y, Cramer M, Randlett A, Thiele BL. Long-term sequelae of acute venous thrombosis. JAMA. 1983 Sep 9. 250(10):1289-92. [QxMD MEDLINE Link].
Prandoni P, Lensing AW, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med. 1996 Jul 1. 125(1):1-7. [QxMD MEDLINE Link].
Meissner MH, Caps MT, Zierler BK, Bergelin RO, Manzo RA, Strandness DE Jr. Deep venous thrombosis and superficial venous reflux. J Vasc Surg. 2000 Jul. 32(1):48-56. [QxMD MEDLINE Link].
Meissner MH, Caps MT, Zierler BK, et al. Determinants of chronic venous disease after acute deep venous thrombosis. J Vasc Surg. 1998 Nov. 28(5):826-33. [QxMD MEDLINE Link].
Meissner MH, Manzo RA, Bergelin RO, Markel A, Strandness DE Jr. Deep venous insufficiency: the relationship between lysis and subsequent reflux. J Vasc Surg. 1993 Oct. 18(4):596-605; discussion 606-8. [QxMD MEDLINE Link].
Caps MT, Manzo RA, Bergelin RO, Meissner MH, Strandness DE Jr. Venous valvular reflux in veins not involved at the time of acute deep vein thrombosis. J Vasc Surg. 1995 Nov. 22(5):524-31. [QxMD MEDLINE Link].
Johnson BF, Manzo RA, Bergelin RO, Strandness DE Jr. Relationship between changes in the deep venous system and the development of the postthrombotic syndrome after an acute episode of lower limb deep vein thrombosis: a one- to six-year follow-up. J Vasc Surg. 1995 Feb. 21(2):307-12; discussion 313. [QxMD MEDLINE Link].
Johnson BF, Manzo RA, Bergelin RO, Strandness DE Jr. The site of residual abnormalities in the leg veins in long-term follow-up after deep vein thrombosis and their relationship to the development of the post-thrombotic syndrome. Int Angiol. 1996 Mar. 15(1):14-9. [QxMD MEDLINE Link].
Haenen JH, Wollersheim H, Janssen MC, et al. Evolution of deep venous thrombosis: a 2-year follow-up using duplex ultrasound scan and strain-gauge plethysmography. J Vasc Surg. 2001 Oct. 34(4):649-55. [QxMD MEDLINE Link].
Andriopoulos A, Wirsing P, Botticher R. Results of iliofemoral venous thrombectomy after acute thrombosis: report on 165 cases. J Cardiovasc Surg (Torino). 1982 Mar-Apr. 23(2):123-4. [QxMD MEDLINE Link].
Zheng Y, Zhou B, Pu X. [Frequency of protein C polymorphisms in Chinese population and thrombotic patients]. Zhonghua Yi Xue Za Zhi. 1998 Mar. 78(3):210-2. [QxMD MEDLINE Link].
Juhan C, Alimi Y, Di Mauro P, Hartung O. Surgical venous thrombectomy. Cardiovasc Surg. 1999 Oct. 7(6):586-90. [QxMD MEDLINE Link].
Saarinen J, Kallio T, Lehto M, Hiltunen S, Sisto T. The occurrence of the post-thrombotic changes after an acute deep venous thrombosis. A prospective two-year follow-up study. J Cardiovasc Surg (Torino). 2000 Jun. 41(3):441-6. [QxMD MEDLINE Link].
Elliott G. Thrombolytic therapy for venous thromboembolism. Curr Opin Hematol. 1999 Sep. 6(5):304-8. [QxMD MEDLINE Link].
Baker WF Jr. Diagnosis of deep venous thrombosis and pulmonary embolism. Med Clin North Am. 1998 May. 82(3):459-76. [QxMD MEDLINE Link].
Henriksen O, Sejrsen P. Effect of "vein pump" activation upon venous pressure and blood flow in human subcutaneous tissue. Acta Physiol Scand. 1977 May. 100(1):14-21. [QxMD MEDLINE Link].
Kearon C. Initial treatment of venous thromboembolism. Thromb Haemost. 1999 Aug. 82(2):887-91. [QxMD MEDLINE Link].
Kakkar VV, Howes J, Sharma V, Kadziola Z. A comparative double-blind, randomised trial of a new second generation LMWH (bemiparin) and UFH in the prevention of post-operative venous thromboembolism. The Bemiparin Assessment group. Thromb Haemost. 2000 Apr. 83(4):523-9. [QxMD MEDLINE Link].
Heit JA, Mohr DN, Silverstein MD, Petterson TM, O'Fallon WM, Melton LJ 3rd. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study. Arch Intern Med. 2000 Mar 27. 160(6):761-8. [QxMD MEDLINE Link].
Stein PD. Silent pulmonary embolism. Arch Intern Med. 2000 Jan 24. 160(2):145-6. [QxMD MEDLINE Link].
Lewandowski A, Syska-Suminska J, Dluzniewski M. [Pulmonary embolism suspicion in a young female patient with the Paget-von Schrötter syndrome]. Kardiol Pol. 2008 Sep. 66(9):969-71. [QxMD MEDLINE Link].
Acharya G, Singh K, Hansen JB, Kumar S, Maltau JM. Catheter-directed thrombolysis for the management of postpartum deep venous thrombosis. Acta Obstet Gynecol Scand. 2005 Feb. 84(2):155-8. [QxMD MEDLINE Link].
Baarslag HJ, Koopman MM, Hutten BA, et al. Long-term follow-up of patients with suspected deep vein thrombosis of the upper extremity: survival, risk factors and post-thrombotic syndrome. Eur J Intern Med. 2004 Dec. 15(8):503-507. [QxMD MEDLINE Link].
Joffe HV, Kucher N, Tapson VF, Goldhaber SZ. Upper-extremity deep vein thrombosis: a prospective registry of 592 patients. Circulation. 2004 Sep 21. 110(12):1605-11. [QxMD MEDLINE Link].
Martinelli I, Battaglioli T, Bucciarelli P, Passamonti SM, Mannucci PM. Risk factors and recurrence rate of primary deep vein thrombosis of the upper extremities. Circulation. 2004 Aug 3. 110(5):566-70. [QxMD MEDLINE Link].
Beyth RJ, Cohen AM, Landefeld CS. Long-term outcomes of deep-vein thrombosis. Arch Intern Med. 1995 May 22. 155(10):1031-7. [QxMD MEDLINE Link].
Kistner RL, Ball JJ, Nordyke RA, Freeman GC. Incidence of pulmonary embolism in the course of thrombophlebitis of the lower extremities. Am J Surg. 1972 Aug. 124(2):169-76. [QxMD MEDLINE Link].
Havig O. Deep vein thrombosis and pulmonary embolism. An autopsy study with multiple regression analysis of possible risk factors. Acta Chir Scand Suppl. 1977. 478:1-120. [QxMD MEDLINE Link].
Higdon ML, Higdon JA. Treatment of oncologic emergencies. Am Fam Physician. 2006 Dec 1. 74 (11):1873-80. [QxMD MEDLINE Link].
Guijarro Escribano JF, Anton RF, Colmenarejo Rubio A, et al. Superior vena cava syndrome with central venous catheter for chemotherapy treated successfully with fibrinolysis. Clin Transl Oncol. 2007 Mar. 9 (3):198-200. [QxMD MEDLINE Link].
Baltayiannis N, Magoulas D, Anagnostopoulos D, et al. Percutaneous stent placement in malignant cases of superior vena cava syndrome. J BUON. 2005 Jul-Sep. 10 (3):377-80. [QxMD MEDLINE Link].
Urruticoechea A, Mesia R, Dominguez J, et al. Treatment of malignant superior vena cava syndrome by endovascular stent insertion. Experience on 52 patients with lung cancer. Lung Cancer. 2004 Feb. 43 (2):209-14. [QxMD MEDLINE Link].
Satoh K, Satoh T, Yaoita N, Shimokawa H. Recent advances in the understanding of thrombosis. Arterioscler Thromb Vasc Biol. 2019 Jun. 39 (6):e159-65. [QxMD MEDLINE Link]. [Full Text].
Arfvidsson B, Eklof B, Kistner RL, Masuda EM, Sato DT. Risk factors for venous thromboembolism following prolonged air travel. Coach class thrombosis. Hematol Oncol Clin North Am. 2000 Apr. 14(2):391-400, ix. [QxMD MEDLINE Link].
Slipman CW, Lipetz JS, Jackson HB, Vresilovic EJ. Deep venous thrombosis and pulmonary embolism as a complication of bed rest for low back pain. Arch Phys Med Rehabil. 2000 Jan. 81(1):127-9. [QxMD MEDLINE Link].
Ruggeri M, Tosetto A, Castaman G, Rodeghiero F. Congenital absence of the inferior vena cava: a rare risk factor for idiopathic deep-vein thrombosis. Lancet. 2001 Feb 10. 357(9254):441. [QxMD MEDLINE Link].
Hamoud S, Nitecky S, Engel A, Goldsher D, Hayek T. Hypoplasia of the inferior vena cava with azygous continuation presenting as recurrent leg deep vein thrombosis. Am J Med Sci. 2000 Jun. 319(6):414-6. [QxMD MEDLINE Link].
Greenfield LJ, Proctor MC. The percutaneous Greenfield filter: outcomes and practice patterns. J Vasc Surg. 2000 Nov. 32(5):888-93. [QxMD MEDLINE Link].
Tsuji Y, Goto A, Hara I, et al. Renal cell carcinoma with extension of tumor thrombus into the vena cava: surgical strategy and prognosis. J Vasc Surg. 2001 Apr. 33(4):789-96. [QxMD MEDLINE Link].
Stamatakis JD, Kakkar VV, Sagar S, Lawrence D, Nairn D, Bentley PG. Femoral vein thrombosis and total hip replacement. Br Med J. 1977 Jul 23. 2(6081):223-5. [QxMD MEDLINE Link]. [Full Text].
Pullen LC. PICCs may double risk for clots in critically ill patients. Medscape Medical News from WebMD. May 20, 2013. Available at http://www.medscape.com/viewarticle/804428. Accessed: June 4, 2013.
Chopra V, Anand S, Hickner A, et al. Risk of venous thromboembolism associated with peripherally inserted central catheters: a systematic review and meta-analysis. Lancet. 2013 Jul 27. 382(9889):311-25. [QxMD MEDLINE Link].
Alikhan R, Cohen AT, Combe S, et al. Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study. Arch Intern Med. 2004 May 10. 164(9):963-8. [QxMD MEDLINE Link].
Heit JA, Elliott CG, Trowbridge AA, Morrey BF, Gent M, Hirsh J. Ardeparin sodium for extended out-of-hospital prophylaxis against venous thromboembolism after total hip or knee replacement. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000 Jun 6. 132(11):853-61. [QxMD MEDLINE Link].
Chu C, Tokumaru S, Izumi K, Nakagawa K. Obesity increases risk of anticoagulation reversal failure with prothrombin complex concentrate in those with intracranial hemorrhage. Int J Neurosci. 2016 Jan. 126 (1):62-6. [QxMD MEDLINE Link].
Nordstrom M, Lindblad B, Bergqvist D, Kjellstrom T. A prospective study of the incidence of deep-vein thrombosis within a defined urban population. J Intern Med. 1992 Aug. 232(2):155-60. [QxMD MEDLINE Link].
Dahlback B. Inherited thrombophilia: resistance to activated protein C as a pathogenic factor of venous thromboembolism. Blood. 1995 Feb 1. 85(3):607-14. [QxMD MEDLINE Link].
Anderson FA Jr, Wheeler HB, Goldberg RJ, Hosmer DW, Forcier A. The prevalence of risk factors for venous thromboembolism among hospital patients. Arch Intern Med. 1992 Aug. 152(8):1660-4. [QxMD MEDLINE Link].
Warlow C, Ogston D, Douglas AS. Deep venous thrombosis of the legs after strokes. Part I--incidence and predisposing factors. Br Med J. 1976 May 15. 1(6019):1178-81. [QxMD MEDLINE Link]. [Full Text].
Monreal M, Lafoz E, Casals A, et al. Occult cancer in patients with deep venous thrombosis. A systematic approach. Cancer. 1991 Jan 15. 67(2):541-5. [QxMD MEDLINE Link].
Rickles FR, Levine M, Edwards RL. Hemostatic alterations in cancer patients. Cancer Metastasis Rev. 1992 Nov. 11(3-4):237-48. [QxMD MEDLINE Link].
Levine MN, Gent M, Hirsh J, et al. The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer. N Engl J Med. 1988 Feb 18. 318(7):404-7. [QxMD MEDLINE Link].
Clagett GP, Reisch JS. Prevention of venous thromboembolism in general surgical patients. Results of meta-analysis. Ann Surg. 1988 Aug. 208(2):227-40. [QxMD MEDLINE Link]. [Full Text].
Clagett GP, Anderson FA Jr, Heit J, Levine MN, Wheeler HB. Prevention of venous thromboembolism. Chest. 1995 Oct. 108(4 Suppl):312S-334S. [QxMD MEDLINE Link].
Coagulation and thromboembolism in orthopaedic surgery. Beaty JH, ed. Orthopaedic Knowledge Update. Rosemont, IL: Amer Academy of Orthopaedic Surgeons; 1999. 6: 63-72.
Kakkar VV, Howe CT, Nicolaides AN, Renney JT, Clarke MB. Deep vein thrombosis of the leg. Is there a "high risk" group?. Am J Surg. 1970 Oct. 120(4):527-30. [QxMD MEDLINE Link].
Dahlback B. Inherited thrombophilia: resistance to activated protein C as a pathogenic factor of venous thromboembolism. Blood. 1995 Feb 1. 85(3):607-14. [QxMD MEDLINE Link].
Motykie GD, Caprini JA, Arcelus JI, et al. Risk factor assessment in the management of patients with suspected deep venous thrombosis. Int Angiol. 2000 Mar. 19(1):47-51. [QxMD MEDLINE Link].
Motykie GD, Zebala LP, Caprini JA, et al. A guide to venous thromboembolism risk factor assessment. J Thromb Thrombolysis. 2000 Apr. 9(3):253-62. [QxMD MEDLINE Link].
Schafer AI. Hypercoagulable states: molecular genetics to clinical practice. Lancet. 1994 Dec 24-31. 344(8939-8940):1739-42. [QxMD MEDLINE Link].
Meissner MH, Strandness E. Pathophysiology and natural history of acute deep venous thrombosis, Rutherford’s Vascular Surgery. 2005. 2124-2142.
Ho CH, Chau WK, Hsu HC, Gau JP, Yu TJ. Causes of venous thrombosis in fifty Chinese patients. Am J Hematol. 2000 Feb. 63(2):74-8. [QxMD MEDLINE Link].
Vandenbrouke JP, Bloemenkamp KW, Rosendaal FR, Helmerhorst FM. Incidence of venous thromboembolism in users of combined oral contraceptives. Risk is particularly high with first use of oral contraceptives. BMJ. 2000 Jan 1. 320(7226):57-8. [QxMD MEDLINE Link].
Cushman M, Tsai AW, White RH, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology. Am J Med. 2004 Jul 1. 117(1):19-25. [QxMD MEDLINE Link].
Bollen L, Vande Casteele N, Ballet V, et al. Thromboembolism as an important complication of inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2016 Jan. 28 (1):1-7. [QxMD MEDLINE Link].
Sevitt S, Gallagher N. Venous thrombosis and pulmonary embolism. A clinico-pathological study in injured and burned patients. Br J Surg. 1961 Mar. 48:475-89. [QxMD MEDLINE Link].
Gorman WP, Davis KR, Donnelly R. ABC of arterial and venous disease. Swollen lower limb-1: general assessment and deep vein thrombosis. BMJ. 2000 May 27. 320(7247):1453-6. [QxMD MEDLINE Link]. [Full Text].
Martinelli I, Lensing AW, Middeldorp S, et al. Recurrent venous thromboembolism and abnormal uterine bleeding with anticoagulant and hormone therapy use. Blood. 2015 Dec 22. [QxMD MEDLINE Link].
Kearon C, Crowther M, Hirsh J. Management of patients with hereditary hypercoagulable disorders. Annu Rev Med. 2000. 51:169-85. [QxMD MEDLINE Link].
Prandoni P, Mannucci PM. Deep-vein thrombosis of the lower limbs: diagnosis and management. Baillieres Best Pract Res Clin Haematol. 1999 Sep. 12(3):533-54. [QxMD MEDLINE Link].
Rathbun SW, Raskob GE, Whitsett TL. Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med. 2000 Feb 1. 132(3):227-32. [QxMD MEDLINE Link].
Goldhaber SZ. Diagnosis of deep venous thrombosis. Clin Cornerstone. 2000. 2(4):29-37. [QxMD MEDLINE Link].
Signorelli SS, Valerio F, Davide C, et al. Evaluating the potential of routine blood tests to identify the risk of deep vein thrombosis: a 1-year monocenter cohort study. Angiology. 2017 Aug. 68 (7):592-7. [QxMD MEDLINE Link].
Lensing AW. Anticoagulation in acute ischaemic stroke: deep vein thrombosis prevention and long-term stroke outcomes. Blood Coagul Fibrinolysis. 1999 Aug. 10 Suppl 2:S123-7. [QxMD MEDLINE Link].
Lensing AW, Prins MH. Recurrent deep vein thrombosis and two coagulation factor gene mutations: quo vadis?. Thromb Haemost. 1999 Dec. 82(6):1564-6. [QxMD MEDLINE Link].
Kleinjan A, Di Nisio M, Beyer-Westendorf J, et al. Safety and feasibility of a diagnostic algorithm combining clinical probability, d-dimer testing, and ultrasonography for suspected upper extremity deep venous thrombosis: a prospective management study. Ann Intern Med. 2014 Apr 1. 160(7):451-7. [QxMD MEDLINE Link].
Deitelzweig S, Jaff MR. Medical management of venous thromboembolic disease. Tech Vasc Interv Radiol. 2004 Jun. 7(2):63-7. [QxMD MEDLINE Link].
McGarry LJ, Stokes ME, Thompson D. Outcomes of thromboprophylaxis with enoxaparin vs. unfractionated heparin in medical inpatients. Thromb J. 2006 Sep 27. 4:17. [QxMD MEDLINE Link].
Cosmi B, Palareti G. D-dimer, oral anticoagulation, and venous thromboembolism recurrence. Semin Vasc Med. 2005 Nov. 5(4):365-70. [QxMD MEDLINE Link].
Linkins LA, Bates SM, Lang E, et al. Selective D-dimer testing for diagnosis of a first suspected episode of deep venous thrombosis: a randomized trial. Ann Intern Med. 2013 Jan 15. 158(2):93-100. [QxMD MEDLINE Link].
Brown T. Selective D-dimer testing best for DVT diagnosis. Medscape Heartwire from WebMD. January 15, 2013. Available at http://www.medscape.com/viewarticle/791417. Accessed: March 19, 2013.
Perrier A, Desmarais S, Miron MJ, et al. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet. 1999 Jan 16. 353(9148):190-5. [QxMD MEDLINE Link].
Wells PS, Anderson DR, Rodger M, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003 Sep 25. 349(13):1227-35. [QxMD MEDLINE Link].
Nakamura M, Yamada N, Oda E, et al. Predictors of venous thromboembolism recurrence and the bleeding events identified using a Japanese healthcare database. J Cardiol. 2017 Aug. 70 (2):155-62. [QxMD MEDLINE Link].
Ita K. Transdermal delivery of heparin: Physical enhancement techniques. Int J Pharm. 2015 Dec 30. 496 (2):240-9. [QxMD MEDLINE Link].
[Guideline] Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016 Feb. 149 (2):315-52. [QxMD MEDLINE Link]. [Full Text].
Tromeur C, Van Der Pol LM, Couturaud F, Klok FA, Huisman MV. Therapeutic management of acute pulmonary embolism. Expert Rev Respir Med. 2017 Aug. 11 (8):641-8. [QxMD MEDLINE Link].
van der Hulle T, Dronkers CE, Klok FA, Huisman MV. Recent developments in the diagnosis and treatment of pulmonary embolism. J Intern Med. 2016 Jan. 279 (1):16-29. [QxMD MEDLINE Link].
Park J, Byun Y. Recent advances in anticoagulant drug delivery. Expert Opin Drug Deliv. 2015 Dec 23. 1-14. [QxMD MEDLINE Link].
Kabuki T, Nakanishi R, Hisatake S, et al. A treatment strategy using subcutaneous fondaparinux followed by oral rivaroxaban is effective for treating acute venous thromboembolism. J Cardiol. 2017 Aug. 70 (2):163-8. [QxMD MEDLINE Link].
Bijsterveld NR, Moons AH, Boekholdt SM, et al. Ability of recombinant factor VIIa to reverse the anticoagulant effect of the pentasaccharide fondaparinux in healthy volunteers. Circulation. 2002 Nov 12. 106(20):2550-4. [QxMD MEDLINE Link].
Cohen AT, Dobromirski M. The use of rivaroxaban for short- and long-term treatment of venous thromboembolism. Thromb Haemost. 2012 Jun. 107(6):1035-43. [QxMD MEDLINE Link].
Romualdi E, Donadini MP, Ageno W. Oral rivaroxaban after symptomatic venous thromboembolism: the continued treatment study (EINSTEIN-extension study). Expert Rev Cardiovasc Ther. 2011 Jul. 9(7):841-4. [QxMD MEDLINE Link].
Raskob GE, Gallus AS, Pineo GF, et al. Apixaban versus enoxaparin for thromboprophylaxis after hip or knee replacement: pooled analysis of major venous thromboembolism and bleeding in 8464 patients from the ADVANCE-2 and ADVANCE-3 trials. J Bone Joint Surg Br. 2012 Feb. 94(2):257-64. [QxMD MEDLINE Link].
Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. 2010 Dec 23. 363(26):2487-98. [QxMD MEDLINE Link]. [Full Text].
Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6. 375(9717):807-15. [QxMD MEDLINE Link].
US Food and Drug Administration. Supplement approval (apixaban) [letter]. August 19, 2014. Available at http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/202155Orig1s006ltr.pdf. Accessed: August 28, 2014.
Agnelli G, Buller HR, Cohen A, et al, for the AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013 Aug 29. 369 (9):799-808. [QxMD MEDLINE Link]. [Full Text].
Agnelli G, Buller HR, Cohen A, et al, for the AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013 Feb 21. 368 (8):699-708. [QxMD MEDLINE Link]. [Full Text].
Liu X, Thompson J, Phatak H, et al. Extended anticoagulation with apixaban reduces hospitalisations in patients with venous thromboembolism. An analysis of the AMPLIFY-EXT trial. Thromb Haemost. 2015 Dec 22. 115 (1):161-8. [QxMD MEDLINE Link].
Schulman S, Kearon C, Kakkar AK, et al, for the RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10. 361 (24):2342-52. [QxMD MEDLINE Link].
Schulman S, Kakkar AK, Goldhaber SZ, et al, for the RE-COVER II Trial Investigators. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014 Feb 18. 129 (7):764-72. [QxMD MEDLINE Link].
Schulman S, Kearon C, Kakkar AK, et al, for the RE-MEDY Trial Investigators, RE-SONATE Trial Investigators. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013 Feb 21. 368 (8):709-18. [QxMD MEDLINE Link].
US Food and Drug Administration. FDA approves anti-clotting drug Savaysa [news release]. Available at https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm429523.htm. January 8, 2015; Accessed: July 16, 2015.
Buller HR, Decousus H, Grosso MA, for the Hokusai-VTE Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med. 2013 Oct 10. 369 (15):1406-15. [QxMD MEDLINE Link].
US Food and Drug Administration. FDA approved betrixaban (BEVYXXA, Portola) for the prophylaxis of venous thromboembolism (VTE) in adult patients. Available at https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm564422.htm. June 23, 2017; Accessed: June 27, 2017.
Cohen AT, Harrington RA, Goldhaber SZ, et al, for the APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely Ill medical patients. N Engl J Med. 2016 Aug 11. 375 (6):534-44. [QxMD MEDLINE Link]. [Full Text].
Gibson CM, Chi G, Halaby R, et al, for the, APEX Investigators. Extended-duration betrixaban reduces the risk of stroke versus standard-dose enoxaparin among hospitalized medically Ill patients: an APEX trial substudy (acute medically Ill venous thromboembolism prevention with extended duration betrixaban). Circulation. 2017 Feb 14. 135 (7):648-55. [QxMD MEDLINE Link].
Prandoni P, Prins MH, Lensing AW, et al. Residual thrombosis on ultrasonography to guide the duration of anticoagulation in patients with deep venous thrombosis: a randomized trial. Ann Intern Med. 2009 May 5. 150(9):577-85. [QxMD MEDLINE Link].
Schulman S, Granqvist S, Holmstrom M, et al. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. The Duration of Anticoagulation Trial Study Group. N Engl J Med. 1997 Feb 6. 336 (6):393-8. [QxMD MEDLINE Link].
Lee AY, Levine MN, Baker RI, et al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10. 349(2):146-53. [QxMD MEDLINE Link].
Hull R, Pineo G, Mah A, et al. A randomized trial evaluating long term low molecular weight heparin therapy for three months verses intravenous heparin followed by warfarin sodium. Blood 100. 2002. 148a.
Pettila V, Kaaja R, Leinonen P, Ekblad U, Kataja M, Ikkala E. Thromboprophylaxis with low molecular weight heparin (dalteparin) in pregnancy. Thromb Res. 1999 Nov 15. 96(4):275-82. [QxMD MEDLINE Link].
Zidane M, Schram MT, Planken EW, et al. Frequency of major hemorrhage in patients treated with unfractionated intravenous heparin for deep venous thrombosis or pulmonary embolism: a study in routine clinical practice. Arch Intern Med. 2000 Aug 14-28. 160(15):2369-73. [QxMD MEDLINE Link].
Vo T, Vazquez S, Rondina MT. Current state of anticoagulants to treat deep venous thrombosis. Curr Cardiol Rep. 2014 Mar. 16(3):463. [QxMD MEDLINE Link].
Levi M, Eerenberg E, Kamphuisen PW. Bleeding risk and reversal strategies for old and new anticoagulants and antiplatelet agents. J Thromb Haemost. 2011 Sep. 9 (9):1705-12. [QxMD MEDLINE Link].
Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun. 133 (6 suppl):141S-159S. [QxMD MEDLINE Link].
Marshall A, Levine M, Howell ML, et al. Dose-associated pulmonary complication rates after fresh frozen plasma administration for warfarin reversal. J Thromb Haemost. 2015 Dec 8. [QxMD MEDLINE Link].
Purrucker JC, Haas K, Rizos T, et al. Early clinical and radiological course, management, and outcome of intracerebral hemorrhage related to new oral anticoagulants. JAMA Neurol. 2015 Dec 14. 1-10. [QxMD MEDLINE Link].
Aronis KN, Hylek EM. Who, when, and how to reverse non-vitamin K oral anticoagulants. J Thromb Thrombolysis. 2015 Dec 1. 123 (6):1350-61. [QxMD MEDLINE Link].
US Food and Drug Administration. FDA approves Praxbind, the first reversal agent for the anticoagulant Pradaxa [news release]. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm467300.htm. October 16, 2015; Accessed: March 30, 2016.
Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015 Aug 6. 373 (6):511-20. [QxMD MEDLINE Link].
Eikelboom JW, Quinlan DJ, van Ryn J, Weitz JI. Idarucizumab: the antidote for reversal of dabigatran. Circulation. 2015 Dec 22. 132 (25):2412-22. [QxMD MEDLINE Link].
Ansell JE. Universal, class-specific and drug-specific reversal agents for the new oral anticoagulants. J Thromb Thrombolysis. 2016 Feb. 41 (2):248-52. [QxMD MEDLINE Link].
Ghadimi K, Dombrowski KE, Levy JH, Welsby IJ. Andexanet alfa for the reversal of factor Xa inhibitor related anticoagulation. Expert Rev Hematol. 2015 Dec 21. [QxMD MEDLINE Link].
Ansell JE, Bakhru SH, Laulicht BE, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med. 2014 Nov 27. 371 (22):2141-2. [QxMD MEDLINE Link].
Enden T, Haig Y, Klow NE, et al for CaVenT Study Group. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet. 2012 Jan 7. 379(9810):31-8. [QxMD MEDLINE Link].
[Guideline] Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb. 141 (2 suppl):e419S-e496S. [QxMD MEDLINE Link].
Plate G, Akesson H, Einarsson E, Ohlin P, Eklof B. Long-term results of venous thrombectomy combined with a temporary arterio-venous fistula. Eur J Vasc Surg. 1990 Oct. 4(5):483-9. [QxMD MEDLINE Link].
Eklof B, Kistner RL. Is there a role for thrombectomy in iliofemoral venous thrombosis?. Semin Vasc Surg. 1996 Mar. 9(1):34-45. [QxMD MEDLINE Link].
Mewissen MW, Seabrook GR, Meissner MH, Cynamon J, Labropoulos N, Haughton SH. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology. 1999 Apr. 211(1):39-49. [QxMD MEDLINE Link].
Prandoni P, Lensing AW, Prins MH, et al. Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial. Ann Intern Med. 2004 Aug 17. 141(4):249-56. [QxMD MEDLINE Link].
[Guideline] Hirsh J, Guyatt G, Albers GW, Harrington R, Schunemann HJ. Antithrombotic and thrombolytic therapy: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008 Jun. 133 (6 suppl):110S-112S. [QxMD MEDLINE Link].
Partsch H. Ambulation and compression after deep vein thrombosis: dispelling myths. Semin Vasc Surg. 2005 Sep. 18(3):148-52. [QxMD MEDLINE Link].
Kahn SR, Shrier I, Kearon C. Physical activity in patients with deep venous thrombosis: a systematic review. Thromb Res. 2008. 122(6):763-73. [QxMD MEDLINE Link].
Ramos R, Salem BI, De Pawlikowski MP, Coordes C, Eisenberg S, Leidenfrost R. The efficacy of pneumatic compression stockings in the prevention of pulmonary embolism after cardiac surgery. Chest. 1996 Jan. 109(1):82-5. [QxMD MEDLINE Link].
Skillman JJ, Collins RE, Coe NP, et al. Prevention of deep vein thrombosis in neurosurgical patients: a controlled, randomized trial of external pneumatic compression boots. Surgery. 1978 Mar. 83(3):354-8. [QxMD MEDLINE Link].
Kolluri R, Plessa AL, Sanders MC, Singh NK, Lucore C. A randomized study of the safety and efficacy of fondaparinux versus placebo in the prevention of venous thromboembolism after coronary artery bypass graft surgery. Am Heart J. 2016 Jan. 171 (1):1-6. [QxMD MEDLINE Link].
[Guideline] Lim W, Le Gal G, Bates SM, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism. Blood Adv. 2018 Nov 27. 2 (22):3226-56. [QxMD MEDLINE Link]. [Full Text].
[Guideline] American Academy of Family Physicians. Diagnosis of venous thromboembolism - clinical practice guideline (endorsed March 2019). Available at https://www.aafp.org/patient-care/clinical-recommendations/all/venous-thromboembolism1.html. March 2019; Accessed: June 3, 2019.
[Guideline] Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy. Blood Adv. 2018 Nov 27. 2 (22):3257-91. [QxMD MEDLINE Link]. [Full Text].
Brien L. Anticoagulant medications for the prevention and treatment of thromboembolism. AACN Adv Crit Care. 2019 Summer. 30 (2):126-38. [QxMD MEDLINE Link].
Agnelli G, Prandoni P, Santamaria MG, et al. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin Optimal Duration Italian Trial Investigators. N Engl J Med. 2001 Jul 19. 345(3):165-9. [QxMD MEDLINE Link].
Alkjaersig N, Fletcher AP, Sherry S. The mechanism of clot dissolution by plasmin. J Clin Invest. 1959 Jul. 38(7):1086-95. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Qaseem A, Snow V, Barry P, et al for the Joint American Academy of Family Physicians/American College of Physicians Panel on Deep Venous Thrombosis/Pulmonary Embolism. Current diagnosis of venous thromboembolism in primary care: a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians. Ann Fam Med. 2007 Jan-Feb. 5(1):57-62. [QxMD MEDLINE Link]. [Full Text].
Anand SS, Wells PS, Hunt D, Brill-Edwards P, Cook D, Ginsberg JS. Does this patient have deep vein thrombosis?. JAMA. 1998 Apr 8. 279(14):1094-9. [QxMD MEDLINE Link].
Bauer KA, Eriksson BI, Lassen MR, Turpie AG. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. 2001 Nov 1. 345(18):1305-10. [QxMD MEDLINE Link].
Berend KR, Lombardi AV Jr. Multimodal venous thromboembolic disease prevention for patients undergoing primary or revision total joint arthroplasty: the role of aspirin. Am J Orthop (Belle Mead NJ). 2006 Jan. 35(1):24-9. [QxMD MEDLINE Link].
Bergmann JF, Neuhart E. A multicenter randomized double-blind study of enoxaparin compared with unfractionated heparin in the prevention of venous thromboembolic disease in elderly in-patients bedridden for an acute medical illness. The Enoxaparin in Medicine Study Group. Thromb Haemost. 1996 Oct. 76(4):529-34. [QxMD MEDLINE Link].
Bjarnason H, Kruse JR, Asinger DA, et al. Iliofemoral deep venous thrombosis: safety and efficacy outcome during 5 years of catheter-directed thrombolytic therapy. J Vasc Interv Radiol. 1997 May-Jun. 8(3):405-18. [QxMD MEDLINE Link].
Boudes PF. The challenges of new drugs benefits and risks analysis: lessons from the ximelagatran FDA Cardiovascular Advisory Committee. Contemp Clin Trials. 2006 Oct. 27(5):432-40. [QxMD MEDLINE Link].
Breddin HK. Low molecular weight heparins in the prevention of deep-vein thrombosis in general surgery. Semin Thromb Hemost. 1999. 25 Suppl 3:83-9. [QxMD MEDLINE Link].
Bristol-Myers Squibb. US FDA approves Eliquis (apixaban) to reduce the risk of blood clots following hip or knee replacement surgery [press release]. Available at http://news.bms.com/press-release/us-fda-approves-eliquis-apixaban-reduce-risk-blood-clots-following-hip-or-knee-replace. Accessed: March 25, 2014.
Bulger CM, Jacobs C, Patel NH. Epidemiology of acute deep vein thrombosis. Tech Vasc Interv Radiol. 2004 Jun. 7(2):50-4. [QxMD MEDLINE Link].
Burke DT. Prevention of deep venous thrombosis: overview of available therapy options for rehabilitation patients. Am J Phys Med Rehabil. 2000 Sep-Oct. 79(5 Suppl):S3-8. [QxMD MEDLINE Link].
Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep. 126(3 Suppl):401S-428S. [QxMD MEDLINE Link].
Camporese G, Bernardi E, Prandoni P, et al. Low-molecular-weight heparin versus compression stockings for thromboprophylaxis after knee arthroscopy: a randomized trial. Ann Intern Med. 2008 Jul 15. 149(2):73-82. [QxMD MEDLINE Link].
Caprini JA, Arcelus JI, Maksimovic D, Glase CJ, Sarayba JG, Hathaway K. Thrombosis prophylaxis in orthopedic surgery: current clinical considerations. J South Orthop Assoc. 2002 Winter. 11(4):190-6. [QxMD MEDLINE Link].
Cham MD, Yankelevitz DF, Shaham D, et al. Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group. Radiology. 2000 Sep. 216(3):744-51. [QxMD MEDLINE Link].
Chan WS, Spencer FA, Lee AY, et al. Safety of withholding anticoagulation in pregnant women with suspected deep vein thrombosis following negative serial compression ultrasound and iliac vein imaging. CMAJ. 2013 Mar 5. 185(4):E194-200. [QxMD MEDLINE Link]. [Full Text].
Cho JS, Martelli E, Mozes G, Miller VM, Gloviczki P. Effects of thrombolysis and venous thrombectomy on valvular competence, thrombogenicity, venous wall morphology, and function. J Vasc Surg. 1998 Nov. 28(5):787-99. [QxMD MEDLINE Link].
Coche EE, Hamoir XL, Hammer FD, Hainaut P, Goffette PP. Using dual-detector helical CT angiography to detect deep venous thrombosis in patients with suspicion of pulmonary embolism: diagnostic value and additional findings. AJR Am J Roentgenol. 2001 Apr. 176(4):1035-9. [QxMD MEDLINE Link].
Colwell C, Mouret P. Ximelagatran for the prevention of venous thromboembolism following elective hip or knee replacement surgery. Semin Vasc Med. 2005 Aug. 5(3):266-75. [QxMD MEDLINE Link].
Comerota AJ, Throm RC, Mathias SD, Haughton S, Mewissen M. Catheter-directed thrombolysis for iliofemoral deep venous thrombosis improves health-related quality of life. J Vasc Surg. 2000 Jul. 32(1):130-7. [QxMD MEDLINE Link].
Comp PC, Spiro TE, Friedman RJ, et al. Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group. J Bone Joint Surg Am. 2001 Mar. 83-A(3):336-45. [QxMD MEDLINE Link].
Deitelzweig S, Jaff MR. Medical management of venous thromboembolic disease. Tech Vasc Interv Radiol. 2004 Jun. 7(2):63-7. [QxMD MEDLINE Link].
DOULBLE REF141.
Dranitsaris G, Stumpo C, Smith R, Bartle W. Extended dalteparin prophylaxis for venous thromboembolic events: cost-utility analysis in patients undergoing major orthopedic surgery. Am J Cardiovasc Drugs. 2009. 9(1):45-58. [QxMD MEDLINE Link].
Dennis M, Sandercock P, Reid J, Graham C, Forbes J, Murray G. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Lancet. 2013 Aug 10. 382(9891):516-24. [QxMD MEDLINE Link].
Eklof B, Arfvidsson B, Kistner RL, Masuda EM. Indications for surgical treatment of iliofemoral vein thrombosis. Hematol Oncol Clin North Am. 2000 Apr. 14(2):471-82. [QxMD MEDLINE Link].
Epstein NE. Efficacy of pneumatic compression stocking prophylaxis in the prevention of deep venous thrombosis and pulmonary embolism following 139 lumbar laminectomies with instrumented fusions. J Spinal Disord Tech. 2006 Feb. 19(1):28-31. [QxMD MEDLINE Link].
Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008 Jun 26. 358(26):2765-75. [QxMD MEDLINE Link].
Eskeland G, Solheim K, Skjorten F. Anticoagulant prophylaxis, thromboembolism and mortality in elderly patients with hip fractures. A controlled clinical trial. Acta Chir Scand. 1966 Jan-Feb. 131(1):16-29. [QxMD MEDLINE Link].
Fisher CG, Blachut PA, Salvian AJ, Meek RN, O'Brien PJ. Effectiveness of pneumatic leg compression devices for the prevention of thromboembolic disease in orthopaedic trauma patients: a prospective, randomized study of compression alone versus no prophylaxis. J Orthop Trauma. 1995 Feb. 9(1):1-7. [QxMD MEDLINE Link].
Francis CW, Berkowitz SD, Comp PC, et al. Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement. N Engl J Med. 2003 Oct 30. 349(18):1703-12. [QxMD MEDLINE Link].
Gaffney PJ, Creighton LJ, Callus M, Thorpe R. Monoclonal antibodies to crosslinked fibrin degradation products (XL-FDP). II. Evaluation in a variety of clinical conditions. Br J Haematol. 1988 Jan. 68(1):91-6. [QxMD MEDLINE Link].
Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest. 2001 Jan. 119(1 Suppl):132S-175S. [QxMD MEDLINE Link].
Gerotziafas GT, Samama MM. Heterogeneity of synthetic factor Xa inhibitors. Curr Pharm Des. 2005. 11(30):3855-76. [QxMD MEDLINE Link].
Gillies TE, Ruckley CV, Nixon SJ. Still missing the boat with fatal pulmonary embolism. Br J Surg. 1996 Oct. 83(10):1394-5. [QxMD MEDLINE Link].
Ginsberg JS, Turkstra F, Buller HR, MacKinnon B, Magier D, Hirsh J. Postthrombotic syndrome after hip or knee arthroplasty: a cross-sectional study. Arch Intern Med. 2000 Mar 13. 160(5):669-72. [QxMD MEDLINE Link].
Grossman C, McPherson S. Safety and efficacy of catheter-directed thrombolysis for iliofemoral venous thrombosis. AJR Am J Roentgenol. 1999 Mar. 172(3):667-72. [QxMD MEDLINE Link].
Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ 3rd. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med. 2000 Mar 27. 160(6):809-15. [QxMD MEDLINE Link].
Henderson D. DVT in pregnancy ruled out by serial Doppler ultrasound. Medscape Medical News from WebMD. January 14, 2013. Available at http://www.medscape.com/viewarticle/777659. Accessed: March 25, 2014.
Horellou MH, Conrad J, Samama MM. Hull RD, Raskob GE, Pineo GF, eds. Venous Thromboembolism: An Evidence-Based Atlas. Armonk, NY: Futura; 1996.
Hull RD, Pineo GF. Prophylaxis of deep venous thrombosis and pulmonary embolism. Current recommendations. Med Clin North Am. 1998 May. 82(3):477-93. [QxMD MEDLINE Link].
Hull RD, Pineo GF, Francis C, et al. Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients: a double-blind, randomized comparison. North American Fragmin Trial Investigators. Arch Intern Med. 2000 Jul 24. 160(14):2208-15. [QxMD MEDLINE Link].
Hull RD, Pineo GF, Stein PD, et al. Timing of initial administration of low-molecular-weight heparin prophylaxis against deep vein thrombosis in patients following elective hip arthroplasty: a systematic review. Arch Intern Med. 2001 Sep 10. 161(16):1952-60. [QxMD MEDLINE Link].
Hull RD, Raskob GE, Brant RF, Pineo GF, Valentine KA. Relation between the time to achieve the lower limit of the APTT therapeutic range and recurrent venous thromboembolism during heparin treatment for deep vein thrombosis. Arch Intern Med. 1997 Dec 8-22. 157(22):2562-8. [QxMD MEDLINE Link].
Hull RD, Raskob GE, Brant RF, Pineo GF, Valentine KA. The importance of initial heparin treatment on long-term clinical outcomes of antithrombotic therapy. The emerging theme of delayed recurrence. Arch Intern Med. 1997 Nov 10. 157(20):2317-21. [QxMD MEDLINE Link].
Iskander GA, Nelson RS, Morehouse DL, Tenquist JE, Szlabick RE. Incidence and propagation of infrageniculate deep venous thrombosis in trauma patients. J Trauma. 2006 Sep. 61(3):695-700. [QxMD MEDLINE Link].
Kakkar AK, Brenner B, Dahl OE, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008 Jul 5. 372(9632):31-9. [QxMD MEDLINE Link].
Kakkar VV, Adams PC. Preventive and therapeutic approach to venous thromboembolic disease and pulmonary embolism--can death from pulmonary embolism be prevented?. J Am Coll Cardiol. 1986 Dec. 8(6 Suppl B):146B-158B. [QxMD MEDLINE Link].
Katz DS, Hon M. Current DVT imaging. Tech Vasc Interv Radiol. 2004 Jun. 7(2):55-62. [QxMD MEDLINE Link].
Kearon C. Epidemiology of venous thromboembolism. Semin Vasc Med. 2001. 1(1):7-26. [QxMD MEDLINE Link].
Kearon C, Ginsberg JS, Julian JA, et al. Comparison of fixed-dose weight-adjusted unfractionated heparin and low-molecular-weight heparin for acute treatment of venous thromboembolism. JAMA. 2006 Aug 23. 296(8):935-42. [QxMD MEDLINE Link].
Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Aug 14. 349(7):631-9. [QxMD MEDLINE Link].
Kearon C, Julian JA, Newman TE, Ginsberg JS. Noninvasive diagnosis of deep venous thrombosis. McMaster Diagnostic Imaging Practice Guidelines Initiative. Ann Intern Med. 1998 Apr 15. 128(8):663-77. [QxMD MEDLINE Link].
Keeney JA, Clohisy JC, Curry MC, Maloney WJ. Efficacy of combined modality prophylaxis including short-duration warfarin to prevent venous thromboembolism after total hip arthroplasty. J Arthroplasty. 2006 Jun. 21(4):469-75. [QxMD MEDLINE Link].
Knight LC, Baidoo KE, Romano JE, Gabriel JL, Maurer AH. Imaging pulmonary emboli and deep venous thrombi with 99mTc-bitistatin, a platelet-binding polypeptide from viper venom. J Nucl Med. 2000 Jun. 41(6):1056-64. [QxMD MEDLINE Link].
Korelitz BI, Sommers SC. Responses to drug therapy in ulcerative colitis. Evaluation by rectal biopsy and histopathological changes. Am J Gastroenterol. 1975 Nov. 64(5):365-70. [QxMD MEDLINE Link].
Lachiewicz PF, Kelley SS, Haden LR. Two mechanical devices for prophylaxis of thromboembolism after total knee arthroplasty. A prospective, randomised study. J Bone Joint Surg Br. 2004 Nov. 86(8):1137-41. [QxMD MEDLINE Link].
Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008 Jun 26. 358(26):2776-86. [QxMD MEDLINE Link].
Lassen MR, Bauer KA, Eriksson BI, Turpie AG. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet. 2002 May 18. 359(9319):1715-20. [QxMD MEDLINE Link].
Leizorovicz A, Haugh MC, Chapuis FR, Samama MM, Boissel JP. Low molecular weight heparin in prevention of perioperative thrombosis. BMJ. 1992 Oct 17. 305(6859):913-20. [QxMD MEDLINE Link]. [Full Text].
Leonardi MJ, McGory ML, Ko CY. The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis: a systematic review of 33 randomized controlled trials. Arch Surg. 2006 Aug. 141(8):790-7; discussion 797-9. [QxMD MEDLINE Link].
Levine MN, Hirsh J, Gent M, et al. Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med. 1991 Apr 1. 114(7):545-51. [QxMD MEDLINE Link].
Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med. 2003 Dec 2. 139(11):893-900. [QxMD MEDLINE Link].
Lotke PA, Lonner JH. The benefit of aspirin chemoprophylaxis for thromboembolism after total knee arthroplasty. Clin Orthop Relat Res. 2006 Nov. 452:175-80. [QxMD MEDLINE Link].
Loud PA, Katz DS, Bruce DA, Klippenstein DL, Grossman ZD. Deep venous thrombosis with suspected pulmonary embolism: detection with combined CT venography and pulmonary angiography. Radiology. 2001 May. 219(2):498-502. [QxMD MEDLINE Link].
Loud PA, Katz DS, Klippenstein DL, Shah RD, Grossman ZD. Combined CT venography and pulmonary angiography in suspected thromboembolic disease: diagnostic accuracy for deep venous evaluation. AJR Am J Roentgenol. 2000 Jan. 174(1):61-5. [QxMD MEDLINE Link].
Meissner MH, Manzo RA, Bergelin RO, Markel A, Strandness DE Jr. Deep venous insufficiency: the relationship between lysis and subsequent reflux. J Vasc Surg. 1993 Oct. 18(4):596-605; discussion 606-8. [QxMD MEDLINE Link].
Merli GJ. Prophylaxis for deep venous thrombosis and pulmonary embolism in the surgical patient. Clin Cornerstone. 2000. 2(4):15-28. [QxMD MEDLINE Link].
Mewissen MW, Seabrook GR, Meissner MH, Cynamon J, Labropoulos N, Haughton SH. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology. 1999 Apr. 211(1):39-49. [QxMD MEDLINE Link].
Michiels JJ, Oortwijn WJ, Naaborg R. Exclusion and diagnosis of deep vein thrombosis by a rapid ELISA D-dimer test, compression ultrasonography, and a simple clinical model. Clin Appl Thromb Hemost. 1999 Jul. 5(3):171-80. [QxMD MEDLINE Link].
Michota F, Merli G. Anticoagulation in special patient populations: are special dosing considerations required?. Cleve Clin J Med. 2005 Apr. 72 Suppl 1:S37-42. [QxMD MEDLINE Link].
Mismetti P, Quenet S, Levine M, et al. Enoxaparin in the treatment of deep vein thrombosis with or without pulmonary embolism: an individual patient data meta-analysis. Chest. 2005 Oct. 128(4):2203-10. [QxMD MEDLINE Link].
Muntz JE, Friedman RJ, eds. Case Vignettes: Thromboprophylaxis in Arthroscopic Surgery. Elsevier Excerpta Medica. 2006.
Nawaz S, Chan P, Ireland S. Suspected deep vein thrombosis: a management algorithm for the accident and emergency department. J Accid Emerg Med. 1999 Nov. 16(6):440-2. [QxMD MEDLINE Link]. [Full Text].
O'Brien SH, Haley K, Kelleher KJ, Wang W, McKenna C, Gaines BA. Variation in DVT prophylaxis for adolescent trauma patients: a survey of the Society of Trauma Nurses. J Trauma Nurs. 2008 Apr-Jun. 15(2):53-7. [QxMD MEDLINE Link].
Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial. Lancet. 1975 Jul 12. 2(7924):45-51. [QxMD MEDLINE Link].
Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000 Apr 15. 355(9212):1295-302. [QxMD MEDLINE Link].
Prevention of thromboembolism in spinal cord injury. Consortium for Spinal Cord Medicine. J Spinal Cord Med. 1997 Jul. 20(3):259-83. [QxMD MEDLINE Link].
Quinlan DJ, McQuillan A, Eikelboom JW. Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2004 Feb 3. 140(3):175-83. [QxMD MEDLINE Link].
Ramzi DW, Leeper KV. DVT and pulmonary embolism: Part II. Treatment and prevention. Am Fam Physician. 2004 Jun 15. 69(12):2841-8. [QxMD MEDLINE Link].
Rhodes JM, Cho JS, Gloviczki P, Mozes G, Rolle R, Miller VM. Thrombolysis for experimental deep venous thrombosis maintains valvular competence and vasoreactivity. J Vasc Surg. 2000 Jun. 31(6):1193-205. [QxMD MEDLINE Link].
Ridker PM, Goldhaber SZ, Danielson E, et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med. 2003 Apr 10. 348(15):1425-34. [QxMD MEDLINE Link].
Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet. 1999 Apr 3. 353(9159):1167-73. [QxMD MEDLINE Link].
Salvati EA, Pellegrini VD Jr, Sharrock NE, et al. Recent advances in venous thromboembolic prophylaxis during and after total hip replacement. J Bone Joint Surg Am. 2000 Feb. 82(2):252-70. [QxMD MEDLINE Link].
Schiff RL, Kahn SR, Shrier I, et al. Identifying orthopedic patients at high risk for venous thromboembolism despite thromboprophylaxis. Chest. 2005 Nov. 128(5):3364-71. [QxMD MEDLINE Link].
Schweizer J, Kirch W, Koch R, et al. Short- and long-term results after thrombolytic treatment of deep venous thrombosis. J Am Coll Cardiol. 2000 Oct. 36(4):1336-43. [QxMD MEDLINE Link].
Shepard RM Jr, White HA, Shirkey AL. Anticoagulant prophylaxis of thromboembolism in postsurgical patients. Am J Surg. 1966 Nov. 112(5):698-702. [QxMD MEDLINE Link].
Snyder BK. Venous thromboembolic prophylaxis: the use of aspirin. Orthop Nurs. 2008 Jul-Aug. 27(4):225-30; quiz 231-2. [QxMD MEDLINE Link].
Sors H, Meyer G. Place of aspirin in prophylaxis of venous thromboembolism. Lancet. 2000 Apr 15. 355(9212):1288-9. [QxMD MEDLINE Link].
Taillefer R, Edell S, Innes G, Lister-James J. Acute thromboscintigraphy with (99m)Tc-apcitide: results of the phase 3 multicenter clinical trial comparing 99mTc-apcitide scintigraphy with contrast venography for imaging acute DVT. Multicenter Trial Investigators. J Nucl Med. 2000 Jul. 41(7):1214-23. [QxMD MEDLINE Link].
Turpie AG, Bauer KA, Eriksson BI, Lassen MR. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med. 2002 Sep 9. 162(16):1833-40. [QxMD MEDLINE Link].
Turpie AG, Gallus AS, Hoek JA. A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement. N Engl J Med. 2001 Mar 1. 344(9):619-25. [QxMD MEDLINE Link].
Turpie AG, Lassen MR, Davidson BL, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009 May 16. 373(9676):1673-80. [QxMD MEDLINE Link].
Communication about an ongoing safety review: Innohep (tinzaparin sodium injection). U.S. Food and Drug Administration. December 2, 2008. Available at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm136254.htm. Accessed: March 12, 2009.
van Dongen CJ, MacGillavry MR, Prins MH. Once versus twice daily LMWH for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev. 2005 Jul 20. CD003074. [QxMD MEDLINE Link].
Vedantham S, Millward SF, Cardella JF, et al. Society of Interventional Radiology position statement: treatment of acute iliofemoral deep vein thrombosis with use of adjunctive catheter-directed intrathrombus thrombolysis. J Vasc Interv Radiol. 2006 Apr. 17(4):613-6. [QxMD MEDLINE Link].
Verstraete M. Direct thrombin inhibitors: appraisal of the antithrombotic/hemorrhagic balance. Thromb Haemost. 1997 Jul. 78(1):357-63. [QxMD MEDLINE Link].
Weitz JI, Middeldorp S, Geerts W, Heit JA. Thrombophilia and new anticoagulant drugs. Hematology Am Soc Hematol Educ Program. 2004. 424-38. [QxMD MEDLINE Link].
Wells PS, Anderson DR, Rodger MA, et al. A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism. Arch Intern Med. 2005 Apr 11. 165(7):733-8. [QxMD MEDLINE Link].
Wood S. Apixaban (Eliquis) approved for DVT/PE prophylaxis post-hip or knee replacement. Medscape Medical News from WebMD. March 14, 2014. Available at http://www.medscape.com/viewarticle/821991. Accessed: March 25, 2014.
Sundboll J, Hovath-Puho E, Adelborg K, et al. Risk of arterial and venous thromboembolism in patients with atrial fibrillation or flutter: a nationwide population-based cohort study. Int J Cardiol. 2017 Aug 15. 241:182-7. [QxMD MEDLINE Link].
Wijarnpreecha K, Thongprayoon C, Panjawatanan P, Ungprasert P. Hepatitis C virus infection and risk of venous thromboembolism: a systematic review and meta-analysis. Ann Hepatol. 2017 Aug 1. 16 (4):514-20. [QxMD MEDLINE Link].
Mityul M, Kim DJ, Salter A, Yano M. CT IVC venogram: normalized quantitative criteria for patency and thrombosis. Abdom Radiol (NY). 2019 Jun. 44 (6):2262-7. [QxMD MEDLINE Link].

Media Gallery

Deep Venous Thrombosis (DVT). This longitudinal ultrasonographic image reveals a partially recanalized thrombus in the femoral vein at the mid thigh.
Deep Venous Thrombosis (DVT). Note the principal deep veins of the lower extremity.
Deep Venous Thrombosis (DVT). This image demonstrates postphlebitic chronic venous insufficiency with ulceration.
Deep Venous Thrombosis (DVT). This image depicts lipodermatosclerosis caused by DVT.
Deep Venous Thrombosis (DVT). There is a substantial mortality benefit for fibrinolytic therapy compared to anticoagulation in patients with right ventricular strain from pulmonary embolism (Konstantinides, 1997).
Deep Venous Thrombosis (DVT). These sequential images demonstrate treatment of iliofemoral DVT due to May-Thurner (Cockett) syndrome. Far left: View of the entire pelvis reveals iliac occlusion. Middle left: After 12 hours of catheter-directed thrombolysis, an obstruction at the left common iliac vein is evident. Middle right: After 24 hours of thrombolysis, a bandlike obstruction is seen; this is the impression made by the overlying right common iliac artery. Far right: After stent placement, the image shows wide patency and rapid flow through the previously obstructed region. Note that the patient is in the prone position in all views. (Right and left are reversed.)
Deep Venous Thrombosis (DVT). This lower-extremity venogram shows outlining of an DVT in the popliteal vein with contrast enhancement.
Deep Venous Thrombosis (DVT). The lower-extremity venogram reveals a nonocclusive chronic thrombus. The superficial femoral vein (lateral vein) has the appearance of two parallel veins, when in fact it is one lumen containing a chronic linear thrombus. Although the chronic clot is not obstructive after it recanalizes, it effectively causes the venous valves to adhere in an open position, predisposing the patient to reflux in the involved segment.
Deep Venous Thrombosis (DVT). Two views of a commercially available thrombectomy device are shown. The Helix Clot Buster works by creating a vortex with a spinning self-contained propeller that macerates the clot. No thrombolytic agent (ie, tissue plasminogen activator) is necessary when this device is used, but adjunct thrombolytic medications can be useful. Competing devices are available from other manufacturers.
Deep Venous Thrombosis (DVT). Popliteal vein thrombosis with normal compression of the common femoral vein is demonstrated. Image courtesy of Very Special Images with permission from Dr Lennard A Nadalo.
Deep Venous Thrombosis (DVT). Bilateral popliteal vein thrombosis with normal compression of the superficial femoral vein is shown. Image courtesy of Very Special Images with permission from Dr Lennard A Nadalo.
Deep Venous Thrombosis (DVT). Popliteal vein thrombosis is depicted by a Duplex sonogram showing absent flow. Image courtesy of Very Special Images with permission from Dr Lennard A Nadalo.
Deep Venous Thrombosis (DVT). Popliteal vein thrombosis is demonstrated by gray-scale images showing compression failure. Image courtesy of Very Special Images with permission from Dr Lennard A Nadalo.
Deep Venous Thrombosis (DVT). This contrast-enhanced study was obtained through a Mediport placed through the chest wall through the internal jugular vein to facilitate chemotherapy. A thrombus has propagated peripherally from the tip of the catheter in the superior vena cava into both subclavian veins.
Deep Venous Thrombosis (DVT). Superior vena cava syndrome is noted in a patient with lung cancer. The computed tomography scan demonstrates a hypoattenuating thrombus that fills the superior vena cava. The patient was treated with anticoagulation alone.
Deep Venous Thrombosis (DVT). The image shows venous thrombi.
Deep Venous Thrombosis (DVT). A pulmonary embolus is shown.
Deep Venous Thrombosis (DVT). The coagulation pathway is shown.
Deep Venous Thrombosis (DVT). This chart shows postoperative antithrombin III levels.
Deep Venous Thrombosis (DVT). This chart depicts perioperative antithrombin III levels and DVT formation.
Deep Venous Thrombosis (DVT). Lung scans are shown. LPO = left posterior oblique.
Deep Venous Thrombosis (DVT). Spiral computed tomography scan showing a pulmonary thrombus.
Deep Venous Thrombosis (DVT). This is the appearance of a normal pulmonary angiogram.
Deep Venous Thrombosis (DVT). This is a positive pulmonary angiogram.
Deep Venous Thrombosis (DVT). The time course of DVT risk is shown in patients not undergoing treatment for total hip replacement (THR).
Deep Venous Thrombosis (DVT). The computed tomography venogram shows bilateral deep venous thrombosis (arrows).
Deep Venous Thrombosis (DVT). The high-probability perfusion lung scan shows segmental perfusion defects in the right upper lobe and subsegmental perfusion defects in right lower lobe, left upper lobe, and left lower lobe.
Deep Venous Thrombosis (DVT). A normal ventilation scan will make the defects noted in the previous image a mismatch and, hence, a high-probability ventilation-perfusion scan.
Deep Venous Thrombosis (DVT). Anterior views of perfusion and ventilation scans are shown. A perfusion defect is present in the left lower lobe, but perfusion to this lobe is intact, making this a high-probability scan.
Deep Venous Thrombosis (DVT). A segmental ventilation perfusion mismatch is evident in a left anterior oblique projection.
Deep Venous Thrombosis (DVT). This sequence of colored digitized pulmonary angiograms (x-ray) in the front view of the pulmonary arteries in a 43-year-old male patient after a heart attack (cardiac arrest) reveals the presence of a pulmonary embolism with a massive thrombus (clot, dark) in the right and left pulmonary arteries. An outline of the lungs are seen. Image courtesy of Science Source/Zephyr.
Deep Venous Thrombosis (DVT). Hematoxylin and eosin stain. This is a low-power view of a thrombus composed of platelets, fibrin, and leukocytes.

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Author

Kaushal (Kevin) Patel, MD Vascular Surgeon, Kaiser Permanente Los Angeles Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

Linda Jun Chun, MD Vascular and Endovascular Surgeon, Kaiser Permanente, Los Angeles Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP Program Director, Emergency Medicine, Einstein Medical Center Montgomery

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, New York Academy of Medicine, New York Academy of Sciences, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Jason S Chang, MD Clinical Instructor, Department of Emergency Medicine, University of Pittsburgh Medical Center

Jason S Chang, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, Society for Academic Emergency Medicine, Emergency Medicine Residents' Association

Disclosure: Nothing to disclose.

Acknowledgements

Marc D Basson, MD, PhD, MBA, FACS Professor, Chair, Department of Surgery, Assistant Dean for Faculty Development in Research, Michigan State University College of Human Medicine

Marc D Basson, MD, PhD, MBA, FACS is a member of the following medical societies: Alpha Omega Alpha, American College of Surgeons, American Gastroenterological Association, Phi Beta Kappa, and Sigma Xi

Disclosure: Nothing to disclose.

John J Borsa, MD Consulting Staff, Department of Radiology, St Joseph Medical Center

John J Borsa, MD is a member of the following medical societies: American College of Radiology, American Society of Neuroradiology, Cardiovascular and Interventional Radiological Society of Europe, Radiological Society of North America, Royal College of Physicians and Surgeons of Canada, and Society of Interventional Radiology

Disclosure: Nothing to disclose.

Hearns W Charles, MD Assistant Professor of Radiology, New York University School of Medicine; Attending Physician, Division of Vascular and Interventional Radiology, Department of Radiology, New York University Medical Center

Hearns W Charles, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Radiological Society of North America, and Society of Cardiovascular and Interventional Radiology

Disclosure: Nothing to disclose.

Kyung J Cho, MD, FACR William Martel Professor of Radiology, Interventional Radiology Fellowship Director, University of Michigan Health System

Kyung J Cho, MD, FACR is a member of the following medical societies: American College of Radiology, American Heart Association, American Medical Association, American Roentgen Ray Society, Association of University Radiologists, and Radiological Society of North America

Disclosure: Nothing to disclose.

Douglas M Coldwell, MD, PhD Professor of Radiology, Director, Division of Vascular and Interventional Radiology, University of Louisville School of Medicine

Douglas M Coldwell, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American College of Radiology, American Heart Association, American Physical Society, American Roentgen Ray Society, Society of Cardiovascular and Interventional Radiology, Southwest Oncology Group, and Special Operations Medical Association

Disclosure: Sirtex, Inc. Consulting fee Speaking and teaching; DFINE, Inc. Honoraria Consulting

Francis Counselman, MD, FACEP Chair, Professor, Department of Emergency Medicine, Eastern Virginia Medical School

Francis Counselman, MD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, Association of Academic Chairs of Emergency Medicine (AACEM), Norfolk Academy of Medicine, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Paul E Di Cesare, MD, FACS Professor and Chair, Department of Orthopedic Sugery, University of California, Davis, School of Medicine

Paul E Di Cesare, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, and Sigma Xi

Disclosure: Stryker Consulting fee Consulting

Robert S Ennis, MD, FACS Associate Professor, Department of Orthopedic Surgery, University of Miami School of Medicine; President, OrthoMed Consulting Services, Inc

Robert S Ennis, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, and Florida Orthopaedic Society

Disclosure: Nothing to disclose.

Craig F Feied, MD, FACEP, FAAEM, FACPh Professor of Emergency Medicine, Georgetown University School of Medicine; General Manager, Microsoft Enterprise Health Solutions Group

Disclosure: Nothing to disclose.

Luis G Fernandez, MD, KHS, FACS, FASAS, FCCP, FCCM, FICS Assistant Clinical Professor of Surgery and Family Practice, University of Texas Health Science Center; Adjunct Clinical Professor of Medicine and Nursing, University of Texas, Arlington; Chairman, Division of Trauma Surgery and Surgical Critical Care, Chief of Trauma Surgical Critical Care Unit, Trinity Mother Francis Health System; Brigadier General, Texas Medical Rangers, TXSG/MB

Luis G Fernandez, MD, KHS, FACS, FASAS, FCCP, FCCM, FICS is a member of the following medical societies: American Association for the Surgery of Trauma, American College of Chest Physicians, American College of Legal Medicine, American College of Surgeons, American Society of Abdominal Surgeons, American Society of General Surgeons, American Society of General Surgeons, American Society of Law, Medicine & Ethics, American Trauma Society, Association for SurgicalEducation, Association of Military Surgeons of the US, Chicago Medical Society, Illinois State Medical Society, International College of Surgeons, New York Academy of Sciences, Pan American Trauma Society, Society of Critical Care Medicine, Society of Laparoendoscopic Surgeons, Southeastern Surgical Congress, Texas Medical Association, and Undersea and Hyperbaric Medical Society

Disclosure: Nothing to disclose.

Douglas M Geehan, MD Associate Professor, Department of Surgery, University of Missouri at Kansas City

Douglas M Geehan, MD is a member of the following medical societies: American College of Surgeons, American Institute of Ultrasound in Medicine, American Medical Association, Association for Academic Surgery, Phi Beta Kappa, Society of American Gastrointestinal and Endoscopic Surgeons, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

John Geibel, MD, DSc, MA Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director, Surgical Research, Department of Surgery, Yale-New Haven Hospital

John Geibel, MD, DSc, MA is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, and Society for Surgery of the Alimentary Tract

Disclosure: AMGEN Royalty Consulting; ARdelyx Ownership interest Board membership

Harris Gellman, MD Consulting Surgeon, Broward Hand Center; Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami, Leonard M Miller School of Medicine

Harris Gellman, MD is a member of the following medical societies: American Academy of Medical Acupuncture, American Academy of Orthopaedic Surgeons, American Orthopaedic Association, American Society for Surgery of the Hand, and Arkansas Medical Society

Disclosure: Nothing to disclose.

Craig Greben, MD Assistant Professor of Radiology, Hofstra University School of Medicine; Chief, Division of Vascular and Interventional Radiology, North Shore University Hospital

Craig Greben, MD is a member of the following medical societies: Society of Cardiovascular and Interventional Radiology

Disclosure: Nothing to disclose.

Lars Grimm, MD, MHS House Staff, Department of Diagnostic Radiology, Duke University Medical Center

Disclosure: Nothing to disclose.

Michael A Grosso, MD Consulting Staff, Department of Cardiothoracic Surgery, St Francis Hospital

Michael A Grosso, MD is a member of the following medical societies: American College of Surgeons, Society of Thoracic Surgeons, and Society of University Surgeons

Disclosure: Nothing to disclose.

George Hartnell, MBChB Professor of Radiology, Tufts University School of Medicine; Director of Cardiovascular and Interventional Radiology, Department of Radiology, Baystate Medical Center

George Hartnell, MBChB is a member of the following medical societies: American College of Cardiology, American College of Radiology, American Heart Association, Association of University Radiologists, British Institute of Radiology, British Medical Association, Massachusetts Medical Society, Radiological Society of North America, Royal College of Physicians, Royal College of Radiologists, andSociety of Cardiovascular and Interventional Radiology

Disclosure: Nothing to disclose.

Eric K Hoffer, MD Director, Vascular and Interventional Radiology, Associate Professor of Radiology, Section of Angiography and Interventional Radiology, Dartmouth-Hitchcock Medical Center

Eric K Hoffer, MD is a member of the following medical societies: American Heart Association, Radiological Society of North America, Society for Cardiac Angiography and Interventions, and Society of Interventional Radiology

Disclosure: Nothing to disclose.

James Quan-Yu Hwang, MD, RDMS, RDCS, FACEP Staff Physician, Emergency Department, Kaiser Permanente

James Quan-Yu Hwang, MD, RDMS, RDCS, FACEP is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Institute of Ultrasound in Medicine, and Society for Academic Emergency Medicine

Disclosure: 3rd Rock Ultrasound, LLC Salary Speaking and teaching; Schlesinger Associates Consulting fee Consulting; Philips Ultrasound Consulting fee Consulting

Bartholomew Kwan, MBBS, FRCPC, FRCR Staff Radiologist, Department of Medical Imaging, WOHC Brampton Civic Hospital

Bartholomew Kwan, MBBS, FRCPC, FRCR is a member of the following medical societies: American Roentgen Ray Society, Cardiovascular and Interventional Radiological Society of Europe, Radiological Society of North America, Royal College of Physicians and Surgeons of Canada, Royal College of Radiologists, and Society of Interventional Radiology

Disclosure: Nothing to disclose.

William C Manson, MD Director of Emergency Ultrasound, Department of Emergency Medicine, Emory University School of Medicine

William C Manson, MD is a member of the following medical societies: American College of Emergency Physicians, American Institute of Ultrasound in Medicine, Emergency Medicine Residents Association, and Society for Academic Emergency Medicine

Disclosure: The Emergency Ultrasound Course Honoraria Speaking and teaching

Girish R Mood, MBBS, MD, MRCS Fellow, Department of Vascular Medicine, Cleveland Clinic Foundation

Disclosure: Nothing to disclose.

James Naidich, MD Residency Director, North Shore University Hospital; Professor, Department of Radiology, New York University School of Medicine

Disclosure: Nothing to disclose.

Jason J Naidich, MD Assistant Professor of Radiology, New York University School of Medicine; Attending Physician, Division of Vascular and Interventional Radiology, North Shore University Hospital

Disclosure: Nothing to disclose.

Vincent Lopez Rowe, MD Associate Professor of Surgery, Department of Surgery, Division of Vascular Surgery, University of Southern California Medical Center

Vincent Lopez Rowe, MD is a member of the following medical societies: American College of Surgeons, American Heart Association, Pacific Coast Surgical Association, Peripheral Vascular Surgery Society, Society for Clinical Vascular Surgery, Society for Vascular Surgery, and Western Vascular Surgical Society

Disclosure: Nothing to disclose.

Miguel A Schmitz, MD Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports Medicine Clinic

Miguel A Schmitz, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, Arthroscopy Association of North America, and North American Spine Society

Disclosure: Nothing to disclose.

Donald Schreiber, MD, CM Associate Professor of Surgery (Emergency Medicine), Stanford University School of Medicine

Donald Schreiber, MD, CM is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Abbott Point of Care Inc Research Grant and Speakers Bureau Speaking and teaching; Nanosphere Inc Grant/research funds Research; Singulex Inc Grant/research funds Research; Abbott Diagnostics Inc Grant/research funds None

William A Schwer, MD Professor, Department of Family Medicine, Rush Medical College; Chairman, Department of Family Medicine, Rush-Presbyterian-St Luke's Medical Center

William A Schwer, MD is a member of the following medical societies: American Academy of Family Physicians

Disclosure: Nothing to disclose.

Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School

Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Management position; ProceduresConsult.com Royalty Other

Gary P Siskin, MD Professor and Chairman, Department of Radiology, Albany Medical College

Gary P Siskin, MD is a member of the following medical societies: American College of Radiology, Cardiovascular and Interventional Radiological Society of Europe, Radiological Society of North America, and Society of Interventional Radiology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Wai Hong Wilson Tang, MD Associate Professor of Medicine, Section of Heart Failure and Cardiac Transplantation Medicine, Cleveland Clinic Foundation

Wai Hong Wilson Tang, MD is a member of the following medical societies: American College of Cardiology, American Heart Association, Heart Failure Society of America, and International Society for Heart and Lung Transplantation

Disclosure: Abbott Laboratories Grant/research funds Research Supplies; Medtronic Inc Consulting fee Consulting; St Jude Medical Consulting fee Consulting

Anthony Watkinson, MD Professor of Interventional Radiology, The Peninsula Medical School; Consultant and Senior Lecturer, Department of Radiology, The Royal Devon and Exeter Hospital, UK

Anthony Watkinson, MD is a member of the following medical societies: Radiological Society of North America, Royal College of Radiologists, and Royal College of Surgeons of England

Disclosure: Nothing to disclose.

Deep Venous Thrombosis (DVT) Treatment & Management

Approach Considerations

Inpatient Versus Outpatient Treatment

Consultations

General Principles of Anticoagulation

Heparin Use in Deep Venous Thrombosis

Factor Xa and Direct Thrombin Inhibitors

Fondaparinux

Rivaroxaban

Apixaban

Dabigatran

Edoxaban

Betrixaban

Duration of Anticoagulation

Complications of Anticoagulant Therapy

Emerging Anticoagulant Agents

Reversal of Anticoagulation

Heparin

Lower molecular weight heparins

Warfarin

Non–vitamin K antagonist oral anticoagulants (NOACs)

Pharmacologic Thrombolysis

General Principles of Endovascular Intervention

Surgical Thrombectomy

Placement of Inferior Vena Cava Filters

Replacement of Venous Valves

Use of Elastic Compression Stockings

Ambulation

Treatment of Superficial Thrombophlebitis

Treatment of Axillary and Subclavian Vein Thrombosis

Prophylaxis of Deep Venous Thrombosis

Deep Venous Thrombosis (DVT) Treatment & Management

Approach Considerations

Inpatient Versus Outpatient Treatment

Consultations

General Principles of Anticoagulation

Heparin Use in Deep Venous Thrombosis

Factor Xa and Direct Thrombin Inhibitors

Fondaparinux

Rivaroxaban

Apixaban

Dabigatran

Edoxaban

Betrixaban

Duration of Anticoagulation

Complications of Anticoagulant Therapy

Emerging Anticoagulant Agents

Reversal of Anticoagulation

Heparin

Lower molecular weight heparins

Warfarin

Non–vitamin K antagonist oral anticoagulants (NOACs)

Pharmacologic Thrombolysis

General Principles of Endovascular Intervention

Surgical Thrombectomy

Placement of Inferior Vena Cava Filters

Replacement of Venous Valves

Use of Elastic Compression Stockings

Ambulation

Treatment of Superficial Thrombophlebitis

Treatment of Axillary and Subclavian Vein Thrombosis

Prophylaxis of Deep Venous Thrombosis

References

Tables

Contributor Information and Disclosures

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