Version May 2024
INTRODUCTION — Deep vein thrombosis (DVT) and acute pulmonary embolism (PE) are two manifestations of venous thromboembolism. The mainstay of therapy for DVT is anticoagulation, provided there is no contraindication. Thrombolysis is occasionally needed.
An overview of the treatment of lower extremity DVT (distal and proximal), including treatment of special populations of patients with DVT, is discussed in this topic. Initial, long-term, and extended (indefinite) anticoagulation for DVT, as well as the treatment of PE and upper extremity DVT, are discussed in detail separately.
●(See "Venous thromboembolism: Initiation of anticoagulation".)
●(See "Venous thromboembolism: Anticoagulation after initial management".)
●(See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults".)
●(See "Primary (spontaneous) upper extremity deep vein thrombosis", section on 'Approach to treatment' and "Catheter-related upper extremity venous thrombosis in adults", section on 'Treatment'.)
NOMENCLATURE — For the purposes of discussion in this topic, the following terms apply (table 1) [1]:
●Provoked DVT – A provoked DVT is one that is precipitated by a known event (eg, surgery, hospital admission, estrogen). It is also referred to as DVT associated with an identifiable risk factor(s). Risk factors can be transient or persistent. Examples are in the table (table 1).
●Unprovoked DVT – Unprovoked DVT is one that occurs in the absence of identifiable risk factors.
●Proximal DVT – Proximal DVT is one that is located in the popliteal, femoral, or iliac veins (table 2).
●Distal DVT – Isolated distal DVT (also known as calf vein DVT) has no proximal component, is located below the knee, and is confined to the calf veins (peroneal, posterior, anterior tibial, and muscular veins). Most calf vein DVTs are located in the posterior tibial and peroneal veins while anterior tibial and muscular vein DVTs are uncommonly involved; the popliteal vein is not involved.
●Phases of anticoagulation – Long-term anticoagulant therapy is typically administered for a finite period of time beyond initiation, usually three to six months and occasionally up to 12 months. Extended anticoagulation refers to therapy that is administered beyond the finite period, sometimes indefinitely. (See "Venous thromboembolism: Initiation of anticoagulation" and "Venous thromboembolism: Anticoagulation after initial management" and "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation".)
●Direct factor Xa and thrombin inhibitors – Direct factor Xa and thrombin inhibitors have been referred to as newer/novel oral anticoagulants, non-vitamin K antagonist oral anticoagulants, direct oral anticoagulants, and target-specific oral anticoagulants [2,3]. Throughout this topic, we refer to these agents by their pharmacologic class, direct factor Xa and thrombin inhibitors. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects".)
The terms provoked and unprovoked may be falling out of favor and use of other terms such as “transient/reversible provoking risk factor”, “persistent provoking risk factor”, and “no identifiable provoking risk factor” may be preferred (table 1). Further discussion is provided separately. (See "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation", section on 'Identify baseline risk based upon presence or absence of risk factors and number of events'.)
INDICATIONS — Indications for treatment are presented for proximal and distal DVT.
Proximal DVT — For most patients with acute proximal DVT (eg, popliteal, femoral, or iliac vein DVT (table 2)), we recommend anticoagulation rather than no anticoagulation, provided the risk of bleeding is not high (table 3 and algorithm 1). (See 'Assessing bleeding risk' below.)
This approach is supported by one older randomized trial that demonstrated a survival benefit compared with no anticoagulation [4], data that support a low rate of venous thromboembolism (VTE) recurrence in patients treated with variable durations of anticoagulant therapy, and the higher risk of embolization from thrombus located in the proximal veins compared with the distal veins [5,6]. Data are strongest for symptomatic patients compared with asymptomatic patients. The recommendation for asymptomatic patients is based upon indirect evidence from patients with symptomatic proximal DVT and the rationale that regardless of symptoms, proximal DVT is likely to have a high risk of embolization. These data are discussed in detail separately. (See 'Anticoagulant therapy' below and "Venous thromboembolism: Anticoagulation after initial management".)
The greatest benefit of anticoagulation occurs within the first few days or weeks of the initial event. As an example, one meta-analysis of 13 prospective cohort studies and 56 randomized clinical trials reported rates of recurrent VTE and fatal VTE during the first three months of anticoagulant therapy as 3.4 and 0.4 percent, respectively [7,8].
The risk of embolization is higher with proximal than distal DVT. Older studies reported that over 90 percent of acute pulmonary embolism (PE) arise from the proximal veins [5,6]. Another prospective analysis of 1643 patients anticoagulated for acute DVT reported that the mortality rate of proximal DVT is twice that of distal DVT (8 versus 4 percent) [9]; however, most of the excess mortality was cancer-related and not due to PE. Management of distal DVT is discussed below. (See 'Distal DVT' below.)
Distal DVT — The treatment of isolated distal DVT varies among centers and clinicians and represents a major challenge therapeutically (algorithm 2) [10]. We use symptoms as well as other clinical features to help us select patients for therapy. In general, those considered at high risk of embolization should be treated with anticoagulant therapy unless there is a contraindication while those at low risk of embolization may undergo observation with serial ultrasound. What is considered high-risk and low-risk is discussed below. (See 'High risk of embolization: Anticoagulation' below and 'Low risk of embolization: Surveillance' below.)
This approach is based upon the rationale that patients with isolated distal DVT are at lower risk of embolization (approximately half the risk) than those with proximal DVT and that in some patients, distal DVTs resolve spontaneously without therapy [5,6,9,11-23].
When the decision is made to anticoagulate patients with isolated distal DVT, full therapeutic anticoagulation should be administered similar to those with proximal DVT. (See 'Anticoagulant therapy' below and "Venous thromboembolism: Anticoagulation after initial management".)
High risk of embolization: Anticoagulation
Symptomatic patients — For most patients with symptomatic isolated distal DVT of the lower extremity, we suggest therapeutic anticoagulation rather than serial compression ultrasonography, provided the risk of bleeding is not high [10,11,24,25]. (See 'Patients at low risk of bleeding' below and "Venous thromboembolism: Anticoagulation after initial management".)
However, there are exceptions to this general rule of thumb. Some patients with distal DVT who have minor symptoms and who have features that support a low risk of embolization (table 4) may reasonably opt out of anticoagulation and undergo surveillance. Low-risk features are described below. (See 'Low risk of embolization: Surveillance' below and 'Patient selection' below.)
Support for this approach is based upon a presumed higher likelihood of embolization (when compared with asymptomatic patients) and the proven efficacy of anticoagulation in reducing clot extension in this population [11-22,26-28].
●Natural history studies suggest that when left untreated, approximately one-third of patients with symptomatic isolated distal DVT will develop extension into the proximal veins, most often within the first two weeks after diagnosis [12-21].
●Several meta-analyses have reported a reduction in the risk of recurrent VTE and lower rates of propagation in patients with distal DVT who were anticoagulated compared with those who did not receive anticoagulant therapy [10,26,27]. In a meta-analysis of 28 studies of patients with isolated DVT, anticoagulant therapy resulted in a 6 percent reduction in VTE recurrence (2.9 versus 9.1 percent; risk reduction [RR] 0.34, 95% CI 0.15-0.77) [10]. The risk of major bleeding was wide (RR 0.76, 95% CI 0.13-4.62; 0.4 versus 0.8 percent). Mortality was unchanged.
In asymptomatic patients with isolated distal DVT, surveillance is appropriate unless risk factors for proximal extension are present (table 4). (See 'Low risk of embolization: Surveillance' below and 'Evidence of or risk factors for proximal extension' below.)
Evidence of or risk factors for proximal extension — Several factors place patients with distal DVT at risk for embolization and should prompt anticoagulant therapy, regardless of symptoms (table 4). This includes patients with:
●Thrombus extension into or close to (eg, within 1 to 2 cm) the proximal popliteal vein
●Unprovoked DVT (see 'Nomenclature' above)
●D-dimer 500 ng/mL
●Extensive thrombosis involving multiple veins (eg, >5 cm in length, >7 mm in diameter)
●Persistent/irreversible risk factors such as active cancer [29] or prolonged immobility (table 1)
●Prior DVT or PE
●Inpatient status
●Coronavirus disease 2019 (COVID-19)
●Patient preference
Low risk of embolization: Surveillance — For select patients with isolated distal DVT who are considered at low risk of embolization, we suggest surveillance for two weeks with serial lower extremity compressive ultrasound (CUS) to look for extension of thrombus into the proximal veins (table 2).
Patient selection — Suitable candidates for surveillance include patients with any one or more of the following (table 4):
●Minor thrombosis in the muscular veins
●A negative D-dimer level (<500 ng/mL)
●Nondiagnostic ultrasonography results
●No symptoms (or minor symptoms)
●No risk factors for proximal extension (see 'Evidence of or risk factors for proximal extension' above)
●High risk of or contraindications to bleeding (see 'Patients at high risk of bleeding' below)
●Patient preference
Patients with isolated distal DVT who are at high risk of bleeding or have a strong preference not to receive anticoagulant therapy should also undergo surveillance off of anticoagulation.
Support for this approach is derived from several retrospective and prospective observational studies, which have reported that limited thrombosis confined to the muscular veins has a low risk of extension without therapy compared with extensive thrombosis of multiple calf veins (approximately 3 versus 15 percent) [11-14,16,19,20,25]. In addition, natural history studies suggest that if extension does not occur within two weeks of diagnosis, it is unlikely to occur [12-21].
Surveillance ultrasound protocol — The optimal frequency, duration, and method of surveillance are unknown. We generally survey patients for thrombus extension or resolution with proximal CUS once a week for two weeks, or earlier if patients develop worsening or new symptoms [10].
For surveillance, we prefer proximal rather than whole leg CUS because it is sufficient for the detection of proximal DVT, where the indication for anticoagulation is strong. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Diagnostic ultrasonography suspected first DVT'.)
Surveillance follow-up — Based upon the results of CUS, the following is appropriate:
●If thrombus resolves, no anticoagulation is required.
●If thrombus extension into the proximal veins is observed, patients should be anticoagulated or treated with an inferior vena cava filter when a contraindication to anticoagulation exists. (See 'Patients at low risk of bleeding' below and 'Patients at high risk of bleeding' below.)
●If thrombus extends toward the proximal veins (eg, within 1 to 2 cm) but remains confined to the calf, we suggest anticoagulation rather than continued surveillance with CUS. (See 'Patients at low risk of bleeding' below.)
●For patients in whom clot does not resolve but remains stable, longer periods of surveillance may be required.
ASSESSING BLEEDING RISK — In all patients with DVT in whom anticoagulation is newly indicated, the decision to anticoagulate should be individualized and the benefits of embolization prevention carefully weighed against the risk of bleeding (table 3 and table 5). Most clinicians agree with the following [11,30,31]:
●Low risk – Patients with a three-month bleeding risk less than 2 percent (low risk) should be anticoagulated.
●High risk – Patients with a bleeding risk more than 13 percent (high risk) should not be anticoagulated.
●Moderate risk – For patients with a bleeding risk between these values (moderate risk), there is no agreement regarding the preferred approach such that the decision to anticoagulate in this population must be individualized according to the values and preferences of the patient as well as the risk-benefit ratio, which may change over time.
Tools are available for estimating the risk of bleeding in anticoagulated individuals. However, no one index can reliably predict bleeding risk in a particular patient such that for practical purposes, many clinicians use a gestalt estimate to assess the bleeding risk. A venous thromboembolism (VTE) specific bleeding score has been generated (VTE-Bleed) using data derived from randomized trials that studied the direct oral thrombin inhibitor, dabigatran, as an anticoagulant for VTE [30]; however, VTE-Bleed requires external validation before it can be recommended for bleeding assessment in patients undergoing initial anticoagulation. Details regarding the use of scoring systems that estimate the risk of bleeding and bleeding risk assessment for those in whom indefinite anticoagulation is being considered are discussed separately. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Bleeding risk scores' and "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation", section on 'Assessing the risk of bleeding'.)
PATIENTS AT LOW RISK OF BLEEDING — For most patients with DVT of the lower extremity who are at low bleeding risk, anticoagulation is the mainstay of therapy, provided there are no contraindications. The primary objective of anticoagulation is the prevention of further propagation and complications of DVT such as acute pulmonary embolism (PE), recurrent DVT, post-thrombotic (postphlebitic) syndrome, and death.
We treat patients who have a definitive diagnosis of DVT, usually made on compressive ultrasound (CUS) of the lower extremities. When DVT is found incidentally (usually computed tomography [CT]), the diagnosis should be sought using CUS before anticoagulation due to the poorer sensitivity and specificity of CT. The diagnosis of DVT and empiric anticoagulation strategies are discussed separately. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Diagnostic ultrasonography suspected first DVT' and "Venous thromboembolism: Initiation of anticoagulation", section on 'Empiric anticoagulation'.)
Anticoagulant therapy — In most patients, anticoagulant therapy should be started immediately as a delay in therapy may increase the risk of potentially life-threatening embolization [32,33].
●Agent selection – Several factors influence agent choice and are listed in the table (table 6). Selecting an anticoagulant, dosing for parenteral and oral anticoagulants, and empiric anticoagulation are discussed in detail separately. (See "Venous thromboembolism: Initiation of anticoagulation" and "Venous thromboembolism: Anticoagulation after initial management", section on 'Selection of agent'.)
●Duration of therapy – In general, we treat for a minimum of three months. Further discussion on duration of therapy and indications for indefinite anticoagulation are discussed in detail separately. (See "Venous thromboembolism: Anticoagulation after initial management", section on 'Duration of treatment' and "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation".)
Outpatient versus inpatient therapy — Several randomized trials and meta-analyses suggest that, in select patients, treatment at home is safe and effective [11,34-48]. The decision to treat DVT in the outpatient setting should be made in the context of the patient's understanding of the risk-benefit ratio, preferences, and clinical condition. Importantly, anticoagulant therapy should not be delayed while the decision is being made whether to treat the patient at home.
Patient selection — When considering outpatient administration of low molecular weight (LMW) heparin, patient selection is critical:
●Outpatient therapy can be considered when patients have all of the following features (table 7):
•Hemodynamic stability
•A low risk of bleeding
•No severe renal insufficiency
•A practical system in place at home for the administration and surveillance of anticoagulant therapy (eg, good living conditions, caregiver support, phone access, understanding and ability to return to the hospital should deterioration occur)
●Outpatient therapy is not appropriate in patients with any one of the following [49]:
•Massive DVT (eg, iliofemoral DVT, phlegmasia cerulea dolens)
•Concurrent symptomatic PE
•High risk of bleeding on anticoagulant therapy
•Comorbid conditions or other factors that warrant in-hospital care
Agent selection — Selecting an agent for outpatient therapy should be individualized and is dependent upon the risk of bleeding, patient comorbidities, preferences, cost, and convenience. For most patients in whom outpatient therapy is selected, we suggest anticoagulation with either rivaroxaban or apixaban (monotherapy; ie, no need for heparin pretreatment). As alternative regimens, LMW heparin overlapped with warfarin (dual therapy) or pretreatment with LMW heparin followed by the administration of either dabigatran or edoxaban (dual therapy) are both appropriate.
Data that support these regimens are discussed below:
●Rivaroxaban or apixaban monotherapy – Randomized trials of rivaroxaban and apixaban reported efficacy of both of these factor Xa inhibitors as the sole initial anticoagulant (monotherapy; ie, without heparin pretreatment) [50,51]. Although short periods (<48 hours) of heparin were allowed prior to randomization and studies were not specifically performed in the outpatient population, our experience with these agents is that they are safe and effective when administered to the outpatient population. These studies and dosing are discussed in detail separately. (See "Venous thromboembolism: Anticoagulation after initial management", section on 'Direct thrombin and factor Xa inhibitors'.)
●LMW heparin plus warfarin – Evidence to support this combination is derived from randomized trials and meta-analyses that have compared LMW heparin delivered at home following immediate discharge from the emergency or outpatient department or following a brief inpatient stay (eg, one day) [11,41,45]. However, these trials have been intrinsically flawed because of differences in the LMW heparin used, the follow-up therapy used (warfarin and LMW heparin), and randomization strategies. (See "Venous thromboembolism: Anticoagulation after initial management", section on 'Low molecular weight heparin'.)
As an example, one meta-analysis of six randomized trials totaling 1708 patients with acute DVT compared outpatient use of LMW heparin with inpatient IV unfractionated heparin (UFH) [11]. Outpatient therapy with LMW heparin was associated with reductions in the rate of recurrent venous thromboembolism (risk reduction [RR] 0.61, 95% CI 0.42-0.9), major bleeding (RR 0.67, 95% CI 0.33-1.36), and mortality (RR 0.72, 95% CI 0.45-1.15) [45].
Dosing of LMW heparin for outpatients is similar to inpatients. However, for enoxaparin we prefer to use the 1 mg/kg twice daily dosing regimen rather than the 1.5 mg/kg once daily regimen since the twice daily regimen has been better validated. Dosing regimens are discussed separately. (See "Venous thromboembolism: Initiation of anticoagulation", section on 'Dosing'.)
●LMW heparin followed by dabigatran or edoxaban – Randomized trials that support efficacy of this combination only studied efficacy for dabigatran (direct thrombin inhibitor) and edoxaban (factor Xa inhibitor) when patients were treated with these agents following a 5- to 10-day course of a parenteral anticoagulant (usually LMW heparin; ie, dual therapy). Consequently, we suggest that dabigatran and edoxaban not be routinely used as a monotherapy for initial anticoagulation in outpatients but can be used in this setting provided that an initial course of parenteral anticoagulant has been administered [52,53]. These studies, dosing, and how to transition from heparin to these agents are discussed in detail separately. (See "Venous thromboembolism: Anticoagulation after initial management", section on 'Direct thrombin and factor Xa inhibitors'.)
Subcutaneous UFH has not been adequately studied in this population and as such cannot be routinely recommended. (See "Heparin and LMW heparin: Dosing and adverse effects".)
Cost savings due to the avoidance of an inpatient stay is a frequently cited advantage of outpatient anticoagulation, and are estimated to range from $500 to $2500 per patient [41,54-63]. However, these studies have compared LMW heparin with UFH and were limited in their sensitivity analysis.
The outpatient treatment of PE is discussed separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Outpatient anticoagulation'.)
PATIENTS AT HIGH RISK OF BLEEDING — In patients with contraindications or who have a high risk of bleeding with anticoagulation, the following is appropriate:
●For patients with acute proximal DVT of the lower extremity, we recommend prompt placement of an inferior vena cava (IVC) filter.
●Patients with acute distal DVT may be managed with surveillance ultrasonography rather than IVC filter placement.
Details of IVC filter placement are discussed separately. (See 'Inferior vena cava filter' below.)
Contraindications to anticoagulation — Absolute contraindications to anticoagulation include the following:
●Active bleeding
●Severe bleeding diathesis
●Recent, planned, or emergency high bleeding-risk surgery/procedure
●Major trauma
●Acute intracranial hemorrhage
Relative contraindications to anticoagulation include:
●Recurrent bleeding from multiple gastrointestinal telangiectasias
●Intracranial or spinal tumors
●Large abdominal aortic aneurysm with concurrent severe hypertension
●Stable aortic dissection
●Recent, planned, or emergent low bleeding-risk surgery/procedure
Thrombocytopenia is not always a contraindication to anticoagulation (eg, those with counts >50,000/microL). Recommendations for specific patient groups and platelet counts are discussed separately. (See "Anticoagulation in individuals with thrombocytopenia".)
Patients with a history of intracranial hemorrhage (eg, due to aneurysm successfully ablated) may be candidates for anticoagulation, but the decision should be individualized and depends upon the risk of embolic events weighed against the risk of recurrent bleeding. Further details are provided separately. (See "Reversal of anticoagulation in intracranial hemorrhage", section on 'Resumption of anticoagulation' and "Spontaneous intracerebral hemorrhage: Secondary prevention and long-term prognosis", section on 'Anticoagulation'.)
Special consideration should also be given to avoiding anticoagulation, when feasible, in older patients (eg, >65 years) with a history of multiple falls and the presence of more than one factor that elevates the bleeding risk. Such patients are at high risk of bleeding or have a high risk of a catastrophic result should a bleed occur. Consequently, the decision to anticoagulate in these populations should be even more cautious to allow the benefits of VTE prevention to be carefully weighed against the risk of bleeding.
Patients with a recent episode of epistaxis or heavy menstrual bleeding are not generally considered high risk for bleeding and anticoagulation can usually be administered safely in this population.
The management of anticoagulation perioperatively and assessing the risk of bleeding are discussed separately. (See 'Assessing bleeding risk' above and "Perioperative management of patients receiving anticoagulants".)
Inferior vena cava filter — The major purpose of IVC filters is the prevention of thrombus embolization to the lung.
Our approach — The following is our approach to IVC filter placement:
●In patients with acute DVT, we do not routinely insert IVC filters, as stand-alone or adjunctive therapy.
●We typically use IVC filters in patients with acute proximal DVT who have a contraindication to anticoagulant therapy (eg, recent surgery, hemorrhagic stroke, active bleeding) [64]. (See 'Patients at high risk of bleeding' above.)
●We also consider placement of an IVC filter as an adjunct in patients with recurrent embolism despite adequate anticoagulation, particularly patients in whom an additional embolic event would be poorly tolerated (eg, those with poor cardiopulmonary reserve from massive pulmonary embolism [PE] or underlying cardiopulmonary disease, hemodynamically unstable patients).
●The efficacy of IVC filter placement in patients with symptomatic isolated distal DVT is unknown and not generally performed unless the thrombus shows signs of progression during surveillance. (See 'Low risk of embolization: Surveillance' above.)
●For patients in whom an IVC filter is placed and the risk of bleeding is subsequently assessed as low, we typically administer a conventional course of anticoagulation therapy and remove the filter when feasible [11]. (See "Venous thromboembolism: Anticoagulation after initial management".)
Several practical factors that may influence the decision to place an IVC filter should be considered in every patient:
●The site of origin of the embolic event must be such that the filter will provide a beneficial effect. For example, most IVC filters are placed in the infrarenal portion of the IVC. This position will prevent embolization of lower extremity thrombus to the lung but will not be of prophylactic value for thrombus located in the renal veins, a cardiac chamber, or the upper extremity veins.
●IVC filter placement is associated with its own set of complications (eg, guidewire entrapment, local hemorrhage, fracture, embolization) and mortality (0.12 to 0.3 percent) such that weighing these risks against those of recurrence is prudent. (See "Placement of vena cava filters and their complications", section on 'Complications' and "Placement of vena cava filters and their complications", section on 'Mortality'.)
●For patients with PE who do not have proven thrombus in the lower extremities and who have a contraindication to anticoagulation, we typically place an IVC filter. This is because thrombus can quickly reform in the leg veins after embolization and may also remain undetected in the pelvis or calf veins with the potential to embolize. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Inferior vena cava filters'.)
Many types of IVC filters are available, but none is superior to another (table 8). In general, we prefer retrievable IVC filters but retrieval rates are variable [65-68]. Alongside an overall decline in rates of IVC filter placement, there has been a rise in IVC filter retrieval rates [69]. Early consideration of filter retrieval, coupled with communication with the inserting proceduralist, can facilitate IVC filter retrieval.
The placement and complications of IVC filters are discussed separately. (See "Placement of vena cava filters and their complications".)
Efficacy — Retrospective and observational case series report that rates of recurrent PE following IVC filter insertion are low (2 to 4 percent in most series) [64,70-72]. While some cohort studies report lower short-term fatality rates in patients in whom an IVC filter is placed, there is no robust evidence that IVC filters prevent PE-related death [64,73,74].
IVC filters may prevent PE in the short-term but at the expense of an increased rate of DVT. IVC filter insertion has also been associated with thrombosis at the filter insertion site, particularly in those in whom anticoagulation is contraindicated and those with known DVT [70,75-78]:
●In one of the largest trials to date (PREPIC1) that examined the effectiveness of IVC filters, 400 patients with proximal DVT were randomly assigned to either standard anticoagulation alone or anticoagulation plus insertion of an IVC filter [79]. During the first 12 days after randomization, significantly fewer patients in the IVC filter group developed a PE (1 versus 5 percent). However, after a two-year follow-up period, there were no significant differences in survival or symptomatic PE between the two groups, and a significantly higher rate of DVT was observed among patients who had received an IVC filter (21 versus 12 percent). An eight-year follow-up of the same population of patients confirmed these findings that filter placement was associated with a successful reduction in the rate of PE (15 versus 6 percent) but an increase in the rate of DVT (35 versus 28 percent) [80]. No difference in mortality was reported. Whether the increased rates of DVT were reflective of older nonretrievable filters is unclear.
The efficacy of IVC filters in patients with PE who have contraindications to anticoagulation are provided separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Inferior vena cava filter'.)
●A review of retrospective case series reported that venous thrombosis at the site of insertion occurred in 10 percent of patients who had an IVC filter placed for a contraindication to anticoagulation [70].
●A prospective observational study of patients in whom permanent filters were placed reported that filter thrombosis occurred in 30 percent, DVT in 20 percent, and PE in 5 percent [76].
The risk of post-thrombotic syndrome (PTS) may also be increased in patients who receive an IVC filter. Two systematic reviews in patients in whom a permanent filter was placed for primary or secondary prevention reported high rates of the signs and symptoms of PTS (50 and 20 percent, respectively) [76,77].
Whether the use of retrievable filters reduce the risk of filter-associated DVT is unknown.
SPECIAL POPULATIONS — Special populations of patients with acute DVT require specific consideration (table 6) and are mostly discussed in the linked sections below.
Patients with malignancy — (See "Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy".)
Antiphospholipid syndrome — (See "Management of antiphospholipid syndrome".)
Pregnancy — (See "Venous thromboembolism in pregnancy and postpartum: Treatment" and "Use of anticoagulants during pregnancy and postpartum".)
Children — (See "Venous thrombosis and thromboembolism (VTE) in children: Risk factors, clinical manifestations, and diagnosis" and "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome".)
May-Thurner syndrome — (See "May-Thurner syndrome".)
Phlegmasia cerulea dolens — (See 'Thrombolytic therapy and thrombectomy' below and "Catheter-directed thrombolytic therapy in deep venous thrombosis of the lower extremity: Patient selection and administration" and "Phlegmasia and venous gangrene".)
Heparin-induced thrombocytopenia — For patients with a DVT and a diagnosis of heparin-induced thrombocytopenia (HIT), all forms of heparin should be discontinued. This includes unfractionated heparin, low molecular weight heparin, heparin flushes, heparin-bonded catheters, and heparin-containing medications. Immediate anticoagulation with a nonheparin anticoagulant (eg, argatroban, danaparoid, fondaparinux) is indicated, unless there is a strong contraindication to anticoagulation. The diagnosis and management of patients with HIT are discussed in detail separately. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia" and "Management of heparin-induced thrombocytopenia".)
Inherited thrombophilias — In many cases, the presence of an inherited thrombophilia does not appreciably alter treatment decisions, such as choice of an anticoagulant or duration of anticoagulation, but there may be specific circumstances in which the thrombophilia does affect management (eg, need for antithrombin [AT] administration in some individuals with AT deficiency). Details are presented in separate topic reviews:
●Factor V Leiden – (See "Factor V Leiden and activated protein C resistance", section on 'Patients with VTE'.)
●Prothrombin G20210A mutation – (See "Prothrombin G20210A", section on 'Patients with VTE'.)
●Protein S deficiency – (See "Protein S deficiency", section on 'Patients with VTE'.)
●Protein C deficiency – (See "Protein C deficiency", section on 'Thromboembolism management'.)
●Antithrombin deficiency – (See "Antithrombin deficiency", section on 'VTE treatment (hereditary deficiency)'.)
SUPPORTIVE THERAPIES — Additional considerations for patients diagnosed with acute DVT of the lower extremity include ambulation and graduated compression stockings (GCS) for the prevention of post-thrombotic (postphlebitic) syndrome (PTS).
Ambulation — In patients with acute DVT, we encourage early ambulation as soon as is feasible, provided the patient is therapeutically anticoagulated. From a practical standpoint, patients with severe DVT or phlegmasia cerulea dolens may be confined to bed for the first 24 hours since ambulation may be difficult or painful.
This approach is supported by several small randomized studies and meta-analyses that have shown that early ambulation does not increase the risk of recurrent or fatal pulmonary embolism (PE) [34,35,81-89].
The risk of PE during more aggressive forms of exercise, physical therapy, or rehabilitation is unknown. However, in this setting we typically gradually increase exercise training as tolerated by the patient.
When symptoms such as pain or leg edema limit ambulation, GCS may be useful for symptomatic relief to facilitate ambulation.
Graduated compression stockings — While elastic GCS that provide 30 to 40 mmHg of ankle pressure have traditionally been used to prevent PTS, we do not routinely use elastic GCS for this purpose. This preference is based upon randomized studies that have not shown clear consistent benefit from GCS in this setting. However, if the decision is made to use GCS, they should be started after anticoagulant therapy, within two weeks of the diagnosis, and continued for two years.
Evidence evaluating elastic GCS for the prevention of PTS is conflicting, with smaller trials suggesting benefit and one large randomized trial reporting no benefit [11,61,90-101].
●While a meta-analysis of five randomized trials reported marginal benefit with elastic GCS (risk ratio 0.62, 95% CI 0.38-1.01), the quality of evidence was low and the benefit is questionable [101]. Most trials were hampered by methodologic flaws, including imprecision, heterogeneity (eg, differing criteria for the assessment of PTS [Ginsberg or Villalta criteria]), risk of bias (lack of blinding, variable initial randomization periods and control groups [eg, no stockings, stockings with 5 mmHg pressure at the ankles, GCS one to two sizes too big]).
●However, the one well-conducted randomized placebo-controlled trial of 806 patients with first proximal DVT reported no difference in the rate of PTS with GCS as measured by the less stringent Ginsberg criteria (leg pain and swelling one month or more; 14 versus 13 percent) [98]. A similar lack of benefit was reported when the more rigorous Villalta criteria were applied. Based upon this study, we and other experts do not routinely apply GCS for the prevention of PTS.
●Older and smaller randomized trials of patients with acute DVT (first or recurrent) that used the Villalta criteria for PTS suggested that GCS that apply an ankle pressure of 30 to 40 mmHg started within two weeks and continued for two years reduced the occurrence of PTS by 50 percent without increasing the frequency of recurrent venous thromboembolism [91,92]. Patients most likely to benefit included patients with a proximal DVT or prior DVT and those with symptoms.
Although GCS are not harmful, many patients also decline their use because they are uncomfortable, costly, inconvenient, and often require a healthcare giver for their application. However, a subset of patients with recurrent DVT or moderate to severe symptoms may consider the potential benefits of GCS to outweigh these inconveniences. In such patients, the purpose of GCS is often focused on symptom reduction rather than PTS prevention.
When the decision is made to wear GCS, they should be started after anticoagulant therapy. This is to avoid the theoretical risk of provoking embolism to the lung from fresh thrombus in the lower extremity. GCS should be continued for two years, replaced every six months, and may require refitting once local swelling is reduced. Alternative approaches of compressive bandages or application of GCS for limited periods (eg, for the duration of anticoagulation) or following thrombolytic therapy have not been adequately evaluated.
Contraindications to GCS include skin ulceration, severe arterial insufficiency, allergy to the stocking material, and inability to apply stockings.
The use of compression stockings as a therapy for PTS is discussed separately. (See "Post-thrombotic (postphlebitic) syndrome", section on 'Compression therapy'.)
THROMBOLYTIC THERAPY AND THROMBECTOMY — For most patients with acute lower extremity DVT, anticoagulant therapy alone is sufficient. Routine use of thrombolytic therapy (systemic and catheter-directed) and/or thrombectomy (surgical or catheter-directed) is not indicated.
●Thrombolysis (usually catheter-directed) is usually reserved for patients with phlegmasia cerulea dolens or massive iliofemoral DVT or for patients who fail therapeutic anticoagulation. Further details are provided separately. (See "Catheter-directed thrombolytic therapy in deep venous thrombosis of the lower extremity: Patient selection and administration" and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Embolectomy'.)
●Thrombectomy (can be performed via a catheter [eg, suction thrombectomy] or by open surgery) may be the only option in patients who are not suitable candidates for or fail thrombolysis. (See "Catheter-directed thrombolytic therapy in deep venous thrombosis of the lower extremity: Patient selection and administration", section on 'Patients at high risk of bleeding or contraindications to thrombolysis' and "Catheter-directed thrombolytic therapy in deep venous thrombosis of the lower extremity: Patient selection and administration", section on 'Patients who fail thrombolysis'.)
Choosing among these options is often at the discretion of the clinician and dependent upon local expertise and clinical factors, such as contraindications and comorbidities.
MONITORING AND FOLLOW-UP — We monitor patients for the complications of both DVT and anticoagulation.
Complications of DVT include further thrombus extension, recurrence, embolization, and post-thrombotic (postphlebitic) syndrome. To this end, we monitor clinically for symptoms. We do not routinely follow-up with lower extremity compression ultrasound following anticoagulant therapy unless the patient has symptoms or signs of recurrent or persistent DVT, although this practice varies among clinicians. Details regarding clinical suspicion for recurrence, pulmonary embolism, and the implications of detecting residual vein obstruction after therapy are discussed separately. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Suspected recurrent DVT' and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation", section on 'Less well-validated risk factors'.)
We also monitor for anticoagulation-related adverse effects (eg, bleeding, thrombocytopenia) and for the development of conditions that affect the half-life of or contraindications for the anticoagulant used (eg, renal failure, pregnancy, weight gain/loss). Further details regarding monitoring patients on anticoagulant therapy are discussed separately. (See "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects" and "Heparin and LMW heparin: Dosing and adverse effects", section on 'Laboratory monitoring/measurement (LMW heparins)' and "Clinical use of coagulation tests", section on 'Anticoagulant monitoring' and "Venous thromboembolism: Anticoagulation after initial management", section on 'Monitoring'.)
EVALUATING FOR AN UNDERLYING CAUSE — Evaluating patients with DVT for an underlying inheritable or acquired risk factor is discussed separately. (See "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Deep vein thrombosis (blood clot in the leg) (The Basics)")
●Beyond the Basics topics (see "Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)" and "Patient education: Warfarin (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Definitions – Proximal deep vein thrombosis (DVT) is one that is located in the popliteal, femoral, or iliac veins (table 2). Distal DVT is confined to the calf veins (peroneal, posterior, anterior tibial, and muscular veins) (table 1). (See 'Nomenclature' above.)
●Patient selection for anticoagulation
•Proximal DVT – The following is our strategy for anticoagulation in patients with proximal DVT (algorithm 1):
-Low risk of bleeding – For most patients with acute proximal DVT of the lower extremity in whom the risk of bleeding is not high (table 3), we recommend therapeutic anticoagulation rather than no anticoagulation (Grade 1B) (algorithm 1). This approach is supported by older data that demonstrated a survival benefit compared with no anticoagulation. In addition, subsequent data support a low rate of venous thromboembolism recurrence in patients treated with variable durations of anticoagulant therapy and the higher risk of embolization from thrombus located in the proximal veins compared with the distal veins. While data are strongest in symptomatic patients, it is reasonable to expect that the same benefit applies to asymptomatic patients.
-High risk of bleeding – For patients with acute proximal DVT of the lower extremity who have contraindications or a high risk of bleeding, we suggest prompt placement of an inferior vena cava (IVC) filter (Grade 2C). This approach is based upon data that suggest low rates of pulmonary embolism (PE) when IVC filters are placed. We prefer retrievable filters for the avoidance of long-term complications of filter placement, particularly recurrent DVT. A conventional course of anticoagulation should be administered once the contraindication resolves. (See 'Patients at high risk of bleeding' above and 'Inferior vena cava filter' above.)
•Distal DVT – The following is our approach to patients with distal DVT of the lower extremity (algorithm 2):
-Low risk of bleeding, high risk of embolization – For patients with distal DVT who are considered to be at high risk of embolization and in whom the risk of bleeding is not high (table 3), we suggest anticoagulation rather than serial monitoring with compression ultrasonography (Grade 2C). This includes most patients who are symptomatic and/or those with features that suggest a high risk of embolization listed on the table (table 4). Support for this approach is based upon a high likelihood of embolization and the proven efficacy of anticoagulation in reducing thrombus extension and subsequent embolization in this population. Occasionally, some patients with minor symptoms who have features that support a low risk of embolization may reasonably opt out of anticoagulation and undergo surveillance. (See 'High risk of embolization: Anticoagulation' above and 'Symptomatic patients' above and 'Evidence of or risk factors for proximal extension' above.)
-Low risk of bleeding and embolization – For most patients with distal DVT who are at low risk of embolization and in whom the risk of bleeding is not high (table 3), we suggest surveillance with serial ultrasound over a two-week period rather than anticoagulation (Grade 2C). Features that are considered to be associated with a low risk of embolization are listed in the table (table 4). For patients who exhibit any signs of thrombus extension during surveillance, we suggest anticoagulation rather than continued surveillance (Grade 2C). This approach is derived from data that suggest a low likelihood of proximal extension (and therefore embolization) without therapy in this population. (See 'Low risk of embolization: Surveillance' above and 'Patient selection' above and 'Surveillance ultrasound protocol' above and 'Surveillance follow-up' above.)
-High risk of bleeding – For patients with acute distal DVT of the lower extremity who have contraindications or a high risk of bleeding, we suggest surveillance ultrasonography rather than IVC filter placement. If a proximal DVT develops, an IVC filter should be placed. (See 'Patients at high risk of bleeding' above.)
●Anticoagulation therapy
•Initial anticoagulation – In most patients, anticoagulation should be started immediately as a delay in therapy increases the risk of potentially life-threatening embolization. Selecting an anticoagulant (table 6), dosing for parenteral and oral anticoagulants, and empiric anticoagulation are discussed in detail separately. (See "Venous thromboembolism: Initiation of anticoagulation" and "Venous thromboembolism: Anticoagulation after initial management", section on 'Selection of agent'.)
•Outpatient anticoagulation – Outpatient anticoagulation rather than inpatient therapy can be considered when patients are hemodynamically stable, have a low risk of bleeding, do not have severe renal insufficiency, and have a practical system in place at home for the administration and surveillance of anticoagulant therapy (table 7). It is not appropriate in patients with massive DVT (eg, iliofemoral DVT, phlegmasia cerulea dolens), concurrent PE, a high risk of bleeding on anticoagulant therapy, comorbid conditions, or other factors that warrant in-hospital care. (See 'Outpatient versus inpatient therapy' above.)
•Long-term anticoagulation – In general, we treat for a minimum of three months. Further discussion on duration of therapy and indications for indefinite anticoagulation are discussed in detail separately. (See "Venous thromboembolism: Anticoagulation after initial management", section on 'Duration of treatment' and "Selecting adult patients with lower extremity deep venous thrombosis and pulmonary embolism for indefinite anticoagulation".)
●Special populations – Special populations of patients with acute DVT that require specific consideration are discussed in the linked topics:
•Malignancy – (See "Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy".)
•Antiphospholipid syndrome – (See "Management of antiphospholipid syndrome".)
•Pregnancy – (See "Anticoagulation therapy for venous thromboembolism (lower extremity venous thrombosis and pulmonary embolism) in adult patients with malignancy" and "Venous thromboembolism in pregnancy and postpartum: Treatment".)
•Children – (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome".)
•May-Thurner syndrome – (See "May-Thurner syndrome".)
•Phlegmasia cerulea dolens – (See 'Thrombolytic therapy and thrombectomy' above and "Catheter-directed thrombolytic therapy in deep venous thrombosis of the lower extremity: Patient selection and administration".)
•Heparin-induced thrombocytopenia – (See "Management of heparin-induced thrombocytopenia".)
•Inherited thrombophilias – Details are presented in separate topic reviews:
-Factor V Leiden – (See "Factor V Leiden and activated protein C resistance", section on 'Patients with VTE'.)
-Prothrombin G20210A mutation – (See "Prothrombin G20210A", section on 'Patients with VTE'.)
-Protein S deficiency – (See "Protein S deficiency", section on 'Patients with VTE'.)
-Protein C deficiency – (See "Protein C deficiency", section on 'Thromboembolism management'.)
-Antithrombin deficiency – (See "Antithrombin deficiency", section on 'VTE treatment (hereditary deficiency)'.)
●Ambulation and graduated compression stockings – For most patients with acute DVT of the lower extremity who are fully anticoagulated, hemodynamically stable, and whose symptoms are under control (eg, pain, swelling), we encourage early ambulation in preference to bed rest. We suggest that elastic graduated compression stockings (GCS) not be administered in patients for the prevention of post-thrombotic (postphlebitic) syndrome (PTS) (Grade 2C). The latter is based upon data from a randomized trial that suggested no benefit from GCS and the observation that many patients decline their use because they are uncomfortable, costly, inconvenient, and often require a healthcare giver for their application. GCS may be applied for symptom control or established PTS, the details of which are discussed separately. (See 'Ambulation' above and 'Graduated compression stockings' above and "Post-thrombotic (postphlebitic) syndrome", section on 'Compression therapy'.)
●Thrombolytic therapy and thrombectomy – For most patients with acute lower extremity DVT, thrombolytic therapy and/or thrombectomy is not indicated. These therapies are usually reserved for patients with phlegmasia cerulea dolens or massive iliofemoral DVT or for patients who fail therapeutic anticoagulation. Thrombolytic therapy is discussed in detail separately. (See "Catheter-directed thrombolytic therapy in deep venous thrombosis of the lower extremity: Patient selection and administration".)
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