Chapter 30. Deep Venous Thrombosis

In the United States, it is estimated that roughly 100 per 100,000 people per year experience a first-time venous thromboembolism (VTE). Of these cases, two thirds are caused by deep venous thrombosis (DVT).1 Much literature has been devoted to the occurrence of VTE in hospitalized patients who are ill or recovering from a surgical procedure. However, many patients present as outpatients to the emergency room with symptoms related to their VTE. This chapter focuses on the current practices for evaluation and diagnosis of DVT and hopes to help guide the emergency physician through the current evidence-based clinical practice guidelines for antithrombotic and thrombolytic therapy.2

Lower extremity DVT is subdivided into proximal (thigh) and distal (calf) vein thrombosis. Proximal DVT is considered of more clinical importance since it is more commonly associated with serious disease and potentially fatal outcomes.

Venous thrombi are composed mainly of fibrin and red blood cells, with the number of platelets and leukocytes being variable. The development, progression, and breakdown of venous thromboemboli reflect a balance between thrombogenic stimuli and protective mechanisms. In the 19th century, Virchow identified and described thrombogenic stimuli. Virchow is credited with outlining the now classic triad of hypercoagulability, endothelial injury, and stasis in association with VTE.3 The presence of the above factors alters the balance between endogenous fibrinolysis and fibrin formation that contributes to the formation and proliferation of a thrombus.1 The protective mechanisms against thromboembolic formation are inactivation of activated coagulation factors by circulating inhibitors such as antithrombin and activated protein C, clearance of activated coagulation factors and soluble fibrin polymer complexes by mononuclear phagocytes and the liver, and plasma and endothelial cell–derived fibrinolytic enzyme lysis of fibrin.4

Using Virchow's triad as a framework, one can better understand the factors that predispose the development of venous thrombosis and the protective mechanisms that counter thrombogenic stimuli. This allows for a better understanding of the various risk factors and treatments for venous thrombi.

Hypercoagulability

The activated clotting factors in blood are regulated by inhibitors on the surface of endothelial cells and circulating antiproteinase. Hypercoagulable states offset the balance and tip the natural clotting cascade in the direction of fibrin production and clot formation. This can be seen as a result of reduced levels of inhibitors or an increase in activated clotting factors. Activation of coagulation may result from the contact of factor XII with collagen on the damaged vessels' exposed subendothelium.5 Malignant cells contain a cysteine protease that can directly activate factor X. This may be one mechanism by which malignancy can induce thrombosis.6 Fibrin formation is enhanced by acquired states of hypercoagulability. Genetic thrombophilias and neoplastic abnormalities increase fibrin formation or decrease fibrinolysis.

Vascular Injury

The processes that initiate a venous thrombosis are less certain and felt to be much different from those that initiate an arterial thrombosis. In arterial thrombosis, a clear relationship between blood vessel injury and thrombus formation has been demonstrated. Following the rupture of an atherosclerotic plaque, the endothelial layer of the vessel is lost, exposing subendothelial ligands such as von Willebrand factor (VWF) and collagen. Platelets have specific receptors for these ligands and therefore bind, signaling additional cofactors and initiating thrombin formation.7,8

The mechanisms by which damage to the venous vessel wall initiates a thrombus formation are less understood. Gross vessel wall injury does not appear to be a prerequisite for venous thrombi formation. A study of 41 autopsies failed to identify any gross vessel wall injury in 49 of 50 lower extremity thrombi.9 However, vascular endothelium can be damaged in other ways: endotoxins, inflammatory cytokines, and hypoxia.

Inflammation results in the activation of the endothelium, which leads to the release of granules that contain VWF and membrane-bound P-selectin. The proteins can attach to the endothelial surface as well as bind leukocytes.7 Leukocytes, in particular monocytes, are able to synthesize tissue factor (TF).10

Additionally there are animal data suggesting that TF-bearing microvesicles may participate in DVT formation. In a mouse model, elevated levels of leukocyte-derived microvesicles were shown to be associated with greater thrombus mass.11 Other studies have demonstrated elevated TF antigen levels and TF–VIIa activity in cancer patients.12 The increased numbers of TF-bearing microvesicles may play a role in the associated hypercoagulability. This theory is supported by autopsy studies that demonstrated DVT not associated with vessel trauma is frequently bilateral.23

Additionally, arterial thrombi cellular composition is different from that of venous thrombi. Platelets compile the core of arterial thrombi and are the cellular components attaching to the vessel wall.13 Venous thrombi are composed predominantly of fibrin, and they are the fibrin-rich regions of the thrombi found at the sight of attachment to the vessel wall.9 The lack of platelets found at the site of attachment of a venous thrombus could explain why antiplatelet drugs have had limited efficacy for venous thrombosis.8

Venous Stasis

Venous stasis leads to an increase in fibrin cross-linking.14 Contraction of the calf muscles enhances venous return from the lower extremities. Blood is propelled upward, preventing pooling in the legs. Stasis, conversely, leads to a reduction in venous blood flow. Diminished blood flow allows the accumulation of prothrombotic substances (such as thrombin) that otherwise would be washed downstream where they are inactivated. In general, thrombin from the lower extremities is washed into the capillary bed of the lung, which has a large surface area coated with antithrombotic substances.7

Venous stasis may also lead to local hypoxia. By allowing stagnation of blood, the hemoglobin in the erythrocytes is desaturated, stimulating hypoxia responses in leukocytes, platelets, and endothelial cells.15 Hypoxia can lead to local ischemia that has been shown to activate the expression of P-selectin on endothelial cells.16 It has been proposed that the expression of P-selectin enables the TF-bearing microvesicles to initiate coagulation and thrombosis.8

There are numerous risk factors that promote the formation of VTE. The major ones are listed in Table 30-1.1,17,18 Ethnicity has also been shown to influence the prevalence of VTE. Hispanics and Asians have a lower adjusted risk of VTE than Caucasians and African Americans.19,20 Advancing age correlates with an increased rate of thromboembolism. An increased occurrence of VTE is observed with each decade over the age of 60.4 Persons under the age of 15 have an incidence of VTE of less than 5 cases per 100,000. After the age of 80, however, the incidence increases to 500 cases per 100,000.21,22

Factor V Leiden is currently recognized as the most common hereditary abnormality predisposing to venous thrombosis. The substitution of glutamine for arginine at residue 506 in the factor V molecule makes factor V resistant to proteolysis by activated protein C.4 The gene mutation follows autosomal dominant inheritance and is more prevalent in Caucasians.23 A patient who is homozygous for the factor V Leiden mutation has a marked increase risk of thromboembolism (estimated 80-fold increase risk) and presents at an earlier age than those who are heterozygous.24Figure 30-1 shows the coagulation pathway and where circulating inhibitors function to protect against thromboembolic formation. Deficiency in circulating inhibitors leads to increased thrombus formation.

Clinical Presentation

The initial symptoms of a DVT are variable and largely nonspecific: cramping, a sense of fullness, paresthesia, or pain in the thigh or calf. A physical examination may reveal unilateral swelling, erythema or discoloration, and warmth of the affected extremity; tenderness to palpation; dilation of superficial collateral veins; and a palpable venous cord. The classic Homan's sign (sharp pain in the calf or posterior aspect of the knee on passive dorsiflexion of the foot) is insensitive and nonspecific.25 A patient with minor signs and symptoms may have extensive DVT, while someone with severe leg pain and swelling may not have a DVT demonstrated by objective testing. Clinical examination is correct only about 50% of the time.

The subtle and nonspecific presentation of a DVT can make it difficult to clinically differentiate the diagnosis from a broad differential diagnosis. Thus, objective testing is needed to confirm or exclude the diagnosis of DVT. Several objective tests are available for establishing the diagnosis of DVT.

D-Dimer

D-dimer (DD) units are produced as the fibrinolytic system degrades cross-linked fibrin. They are generated by the action of factor XIIIa on fibrin monomers and polymers. Monoclonal antibodies in DD assays recognize the fragments from cross-linked fibrin. A small percentage of plasma fibrinogen is physiologically converted to fibrin and then degraded. Thus, small amounts of DD are present in healthy individuals. However, increased concentrations are seen in conditions in which fibrin formation is enhanced and subsequently degraded by plasmin. On average, the plasma level is increased 8-fold in VTE and, moreover, the level falls in parallel with symptom duration and the start of anticoagulant treatment.26 The plasma half-life is approximately 8 hours and DD fragments are cleared by the kidney and reticuloendothelial system.27

The detection of the monoclonal antibody–DD fragment complexes is performed by various techniques: enzyme-linked immunosorbent assay (ELISA), immunofiltration, and sandwich-type or agglutination techniques. Describing the various commercial DD assays is beyond the scope of this text. Each diagnostic system has its own cutoff levels. Clinicians should be knowledgeable of the specific test their facility uses and, furthermore, should only use DD assays that have been appropriately validated in prospective outcome studies.27

A number of clinical conditions increase DD levels: infection, inflammation, cancer, surgery, trauma, extensive burns or bruises, ischemic heart disease, stroke, peripheral artery disease, ruptured aneurysm or aortic dissection, pregnancy, and cerebral sinus thrombosis.26 The diagnostic yield of DD is lower in the elderly as the concentrations of DD rise in the normal aging population. In a cost-effectiveness analysis of a single study of 1,029 patients, one group of investigators demonstrated using DD was cost-saving until the age of 79.28

The objective diagnostic imaging tests currently most useful in diagnosing patients with clinically suspected DVT are ultrasound (US) imaging and venography. Both have been validated through clinical trials that include prospective studies with long-term follow-up establishing the safety of withholding anticoagulation treatment in patients with negative results.

Ultrasound

Venous US has become the standard diagnostic test in patients with a suspected DVT. The two common methods of US used in assessing the presence of DVT are compression US and duplex.

A 2005 meta-analysis examined the diagnostic accuracy of US for DVT as well as performed a separate analysis of different US techniques: (1) compression US only; (2) color Doppler only; (3) continuous wave Doppler only; (4) duplex (combined compression and color Doppler US); (5) triplex (combined compression, color Doppler, and continuous wave Doppler US).29 This study determined diagnostic accuracy varies according to the technique used. Optimal sensitivity was demonstrated by using duplex or triplex US. Optimal specificity was seen by using compression US alone. The authors conclude that compression US alone is probably the appropriate technique for patients with a low probability of DVT, whereas duplex or triplex US would be the appropriate technique when evaluating patients at high risk for DVT or to identify distal DVT.

In compression US, evaluating for a venous thrombosis consists of determining vein patency or the lack thereof (Figure 30-2). To determine venous patency, the gold standard is to determine if the vein collapses completely under pressure, which is directly visualized with US when the lumen disappears entirely (Figures 30-3 and 30-4). Continuous wave Doppler also evaluates blood flow and direction, but as a graphic depiction.31

A duplex US combines color Doppler with compression US. The color Doppler represents flow within a vein. The specific color maps are assigned to a variety of speeds and one of two directions (toward or away from the US transducer).31

Augmentation is a technique to confirm blood flow through a section of an extremity. It utilizes either pulsed wave or color Doppler. While evaluating the proximal portion of a venous segment (e.g., the common femoral vein), the sonographer squeezes the calf that sends a rush of venous blood past the transducer. The increased blood flow is seen on Doppler that is thought to indicate the absence of a completely occlusive thrombus. Patients with venous disease and other comorbidities may lack positive augmentation. Additionally, a partially occluding thrombus or previously established collaterals may still show augmentation.32

Emergency Physicians' Role in Us Diagnosis of DVT

The utilization of the bedside US examination by emergency physicians has evolved from a clinical need to improve efficiency of patient care. Many hospitals do not have vascular laboratory services available during off-hours. This limited availability has resulted in some emergency physicians developing the practice of administering empirical treatment to those patients who are suspected of having a DVT. The patient is then discharged home to return the next day for a formal study. Empirical treatment with anticoagulation involves risk, particularly for patients in whom anticoagulation is problematic. Studies have shown that emergency physicians performing US examinations of the lower extremities themselves decrease time to patient disposition.33 Extensive training is not required. Emergency medicine residents have been shown to be able to perform a limited duplex examination with good accuracy after very limited instruction (90 minutes).34 The increased ability of emergency physicians to perform a bedside US examination will hopefully decrease the practice of empirical treatment with anticoagulation and serve to help discharge patients more quickly who can then obtain a follow-up study as an outpatient.

CT Venography

Using computed tomography (CT) to diagnosis DVT is an area under active investigation. One such example is the PIOPED II study. This prospective multicenter study of 711 patients compared the clinical value of CT venography (CTV) after multidetector CT (MDCT) angiography (CTA) with venous compression sonography for the diagnosis of VTE.35 The investigators demonstrated a 95.5% concordance between CTV and sonography for the diagnosis or exclusion of DVT. They conclude both studies yield equivalent diagnostic results and the choice of imaging techniques should be made on the basis of safety, expense, and time constraints.

Protocols to image the pulmonary arteries and the subdiaphragmatic deep veins (including the legs) should ideally require no additional contrast medium beyond that which is already required for a CT pulmonary angiogram. Yet, not all patients being evaluated for a DVT require a CT pulmonary angiogram. Utilizing CT solely to evaluate for DVT exposes the patient to a radiation dose, potential nephrotoxic intravenous (IV) contrast, and the expense of CT.

MR Venography

The diagnostic accuracy of magnetic resonance (MR) venography is comparable to that of contrast venography (CV), yet outcome data are lacking. Additionally, the high cost of MR venography is a limitation for widespread use. Unlike US, MR imaging (MRI) is able to image the pelvic vasculature and vena cava. MRI does not require the use of ionizing radiation, which makes it an attractive option for certain patient populations such as pregnant patients with suspected VTE.

A prospective single-center study of 24 randomly selected patients compared true fast imaging with steady-state precession (FISP) MR venography for suspected DVT with contrast agent–enhanced venography.36 The authors conclude that MR venography for DVT is sensitive and specific in the pelvis and thigh, but has poor sensitivity below the popliteal vein. Additionally, 11 of the 14 patients without DVT had an alternative diagnosis suggested by MR venography: muscle tear, chronic venous insufficiency secondary to previous DVT, edema, and subcutaneous (SC) fat/fluid artifact related to clinically confirmed congestive cardiac failure or cellulitis. The ability of MR to provide an alternative diagnosis is an added benefit. MR has some disadvantages: transport of a very sick critical care patient to MR can be difficult, some ventilators are not compatible with MR, and an awake patient may suffer from claustrophobia.

Contrast Venography

CV had long been considered the diagnostic test of choice for DVT. However, due to patient discomfort and difficulty in obtaining an adequate study, venography is not recommended as the initial screening test. Noninvasive tests demonstrating equivalent diagnostic accuracy have significantly reduced venography use. Venography is currently reserved for situations in which noninvasive testing is nondiagnostic or impossible to perform. For a CV study to be adequate, complete visualization of the deep venous system (from the calf to the pelvic veins and the inferior vena cava [IVC]) must be obtained37: the internal iliac venous system (hypogastric veins) will not be visualized unless a catheter is directed up into this system. A constant intraluminal filling defect present in two or more views is the most reliable criterion in diagnosing an acute DVT.38

Upper Extremity DVT

Although the majority of DVTs occur in the lower extremities, upper extremity (UE) thrombi are becoming more common than previously thought. There are two forms of UE DVT: (1) effort thrombosis and (2) secondary thrombosis.

Effort thrombosis (Paget–von Schrötter syndrome) is due to an underlying chronic venous compression caused by musculoskeletal variations of the thoracic outlet. The subclavian vein can be compressed by a cervical rib or hypertrophied cervical muscles in the athlete (especially in the weight lifter) during Valsalva maneuver (hence “effort” thrombosis): the sudden stasis of blood leads to thrombosis.

In secondary thrombosis, the increased incidence of UE DVT is most likely a result of increased utilization of central venous catheters, pacemaker wires, and an increase in treated malignancy.31 UE DVTs involve the subclavian, axillary, or brachial veins. Clinical manifestations are similar to those seen in lower extremity DVT and include edema; dilated collateral veins over the arm, neck, or chest; limb pain and discoloration. Pulmonary embolism (PE), recurrent UE DVT, and rarely postthrombotic (phlebitic) syndrome (PTS) of the arms are all potential complications of UE DVTs.2

May–Thurner Syndrome

May–Thurner syndrome is an anatomic pattern in which hemodynamically significant compression of the left common iliac vein occurs between the overlying right common iliac artery and the underlying vertebral body. Most commonly it is seen in women, between the ages of 20 and 50. Typically it presents as either chronic venous insufficiency or a large iliofemoral DVT. The diagnosis should be considered in patients with recurrent left lower extremity DVT or chronic, refractory DVT of the left lower extremity. DVT episodes associated with May–Thurner syndrome can be recurrent and/or not respond to treatment with anticoagulation by itself. Treatment can require catheter-directed thrombolysis (CDT), venous angioplasty, and/or intravascular stenting.39

Phlegmasia Cerulea Dolens

Phlegmasia cerulea dolens is an uncommon form of massive proximal (iliofemoral) venous thrombosis of the lower extremities. Venous obstruction results leading to a sharp rise in venous pressure, massive interstitial fluid shifts, decreased arterial perfusion due to vasospasm from inflammation, compartment syndrome, and gangrene.1 This results in a lower extremity that is tense, cool, swollen, painful, and cyanotic (Figure 30-5).40 The resulting gangrene, compartment syndrome, and arterial compromise can lead to circulatory collapse and shock. Systemic anticoagulation should not be delayed as death or loss of the limb may result. IV thrombolytic therapy's role in treatment is controversial. Emergency thrombectomy should be considered.

The American College of Chest Physicians (ACCP) published their first consensus statement on antithrombotic therapy in 1986. The most recent ACCP guidelines were released in 2008. This section aims to summarize the 2008 ACCP guidelines on therapy for VTE with regards to their application to patients seen by the emergency medicine physician. Unless otherwise referenced, all recommendations are from the 8th Edition ACCP Evidence-Based Clinical Practice Guidelines.2

Briefly, before considering the use of anticoagulant therapy, one must consider if the patient has any contraindications to anticoagulation. The absolute contraindications to anticoagulation treatment include severe active bleeding; intracranial bleeding; recent brain, eye, or spinal cord surgery; and malignant hypertension. Relative contraindications include recent cerebrovascular accident, active gastrointestinal tract bleeding, recent major surgery, severe hypertension, severe renal or hepatic failure, and severe thrombocytopenia (platelets less than 50,000/μL).4

Initial Anticoagulation of Acute DVT of the Leg

The main therapy of acute DVT of the leg is anticoagulation. Initial treatment of this disease aims to prevent thrombus extension as well as early and late recurrences of VTE. As patients treated with vitamin K antagonist (VKA) alone have a high rate of recurrence/extension, it is recommended that heparin (or low-molecular-weight heparin [LMWH] or fondaparinux) is started along with VKA at the time of diagnosis.41 For patients with objectively confirmed DVT, the guidelines recommend five options for the initial treatment of DVT: (1) SC LMWH without monitoring; (2) IV unfractionated heparin (UFH) with monitoring; (3) SC UFH with monitoring; (4) weight-based SC UFH without monitoring; and (5) SC fondaparinux without monitoring. All options were given a Grade 1A recommendation. Additionally, if there is a high clinical suspicion for DVT or a delay before diagnostic testing can be performed, the guidelines recommend treatment with anticoagulants should begin before testing (Grade 1C). The initial treatment with LMWH, UFH, or fondaparinux should continue for at least 5 days and until the international normalized ratio (INR) is ≥2.0 for 24 hours (Grade 1C). This recommendation is based on the observation that, regardless of the INR, factor II activity is not significantly reduced earlier than 5 days after starting warfarin. The combination of a relatively long half-life of factor II and the short half-life of protein C and protein S is thought to provoke a paradoxical hypercoagulable state if heparin/LMWH/fondaparinux is stopped prematurely.41. The initiation of VKA should not be delayed but instead initiated together with LMWH, UFH, or fondaparinux on the first treatment day (Grade 1A). Warfarin can typically be started at a dose of 10 mg in young (less than 60 years), healthy patients and at a dose of 5 mg in older patients and those being hospitalized. The dose of VKA is adjusted to maintain a target INR of 2.5 (range 2.0–3.0) (Grade 1A).

Low-Molecular-Weight Heparin

The guidelines prefer SC LMWH to treatment with IV UFH. They recommend initial treatment with SC LMWH once or twice daily, as an outpatient if possible (Grade 1C), or as an inpatient if necessary (Grade 1A) over treatment with IV UFH. They recommend against routine monitoring with anti–factor Xa level measurements (Grade 1A). However, as LMWH is cleared by the kidneys, in patients with severe renal failure, UFH over LMWH is suggested (Grade 2C).

IV Unfractionated Heparin

The guidelines recommend an initial IV bolus (80 U/kg or 5,000 U), followed by a continuous infusion (initially at a dose of 18 U/kg/h or 1,300 U/h). The dose is then adjusted to achieve and maintain an APPT prolongation that corresponds to therapeutic heparin levels.

Sc Unfractionated Heparin

If monitored SC UFH is chosen, the guidelines recommend an initial dose of 17,500 U, or a weight-adjusted dose of approximately 250U/kg bid. The dose is then adjusted to achieve and maintain an activated partial thromboplastin time (APTT) prolongation corresponding to therapeutic heparin levels (Grade 1C).

If fixed-dose unmonitored SC UFH is selected, the guidelines recommend an initial dose of 333 U/kg followed by a twice-daily dose of 250 U/kg instead of nonweight-based dosing (Grade 1C).

Fondaparinux

Fondaparinux is a synthetic pentasaccharide. Like LMWH, it can be administered SC without monitoring and has been shown to be effective in the treatment of acute DVT (Grade 1A). The disadvantage of fondaparinux is a prolonged half-life (17 hours) and the absence of an antidote.

Treatment Strategies of Thrombus Removal for Acute DVT

Actively removing the thrombi has the potential to decrease acute symptoms and the risk for PTS, and can be limb-saving in phlegmasia cerulea dolens. By removing the thrombus, venous obstruction is reversed and valvular function is restored that may prevent late development of venous valvular incompetence. The guidelines further speculate that thrombus removal and subsequent relief of venous obstruction may reduce the risk of recurrent VTE.

Catheter-Directed Thrombolysis

The guidelines state CDT may be beneficial in select patients: those with symptoms present for less than 14 days, iliofemoral DVT, life expectancy ≥1 year, and good functional status demonstrate a low risk of bleeding. They suggest CT can be utilized to reduce acute symptoms and postthrombotic morbidity at institutions with the appropriate expertise and resources available (Grade 2B). Following successful CDT, the guidelines suggest utilizing balloon angioplasty and stents to correct underlying venous lesions (Grade 2C). If expertise and resources are available, pharmacomechanical thrombolysis (e.g., with inclusion of thrombus fragmentation and/or aspiration) is preferred to CDT alone as it shortens treatment time (Grade 2C). Patients who have undergone successful CDT are still recommended the same intensity and duration of anticoagulant therapy as recommended for those patients who do not receive CDT (Grade 1C).

Systemic Thrombolytic Therapy

For patients with a low risk of bleeding, extensive proximal DVT, symptoms present for less than 14 days, life expectancy ≥1 year, and a good functional status, the guidelines suggest if CDT is not available, systemic thrombolytic therapy may be used to reduce acute symptoms and postthrombotic morbidity (Grade 2C).

Operative Venous Thrombectomy

Operative venous thrombectomy is typically reserved for iliofemoral DVT. For patients with acute iliofemoral DVT, good functional status, life expectancy ≥1 year, and symptoms present for less than 7 days, the guidelines suggest operative venous thrombectomy to decrease acute symptoms as well as postthrombotic morbidity at institutions with appropriate expertise and resources (Grade 2B). However, if patients do not have a high risk of bleeding, the guidelines suggest that CDT is generally preferable to operative venous thrombectomy (Grade 2C). After undergoing operative venous thrombectomy, the guidelines recommend the same intensity and duration of anticoagulant therapy as for those not undergoing venous thrombectomy (Grade 1C).

Vena Caval Filters for the Patient with a DVT

The placement of an IVC filter is not without risk. IVC thrombosis can occur in up to 5% of patients after placement of the filter.40 Currently, no randomized trial has evaluated the efficacy of IVC filters alone (without concurrent anticoagulation) in preventing PE in those with an acute DVT. The guidelines differentiate their recommendations for vena cava filter placement based on the ability to utilize anticoagulation. They recommend against the routine use of a vena cava filter in addition to anticoagulants (Grade 1A). For patients with VTE who cannot receive anticoagulation due to a risk of bleeding, the placement of an IVC filter is recommended (Grade 1C). In addition, for those patients in whom an IVC filter was inserted as an alternative to anticoagulation, the guidelines recommend that that they should subsequently be given a standard course of anticoagulant therapy if their risk of bleeding resolved (Grade 1C).

Duration of Anticoagulant Therapy

In determining the duration of anticoagulant therapy, the ACCP guidelines differentiate acute episode of VTE provoked by a reversible risk factor from those episodes of VTE that are unprovoked (idiopathic VTE). Reversible provoking risk factors include major factors such as surgery, hospitalization, or plaster case immobilization, all within 1 month; and minor factors such as estrogen therapy, pregnancy, prolonged travel (>8 hours), or the previously noted major factors if their occurrence was 1–3 months prior to the diagnosis of VTE. Additional factors considered were if the DVT was confined to the distal veins (isolated calf DVT) and whether the DVT was a first episode of VTE.

• For patients with a DVT secondary to a transient (reversible) risk factor, the recommended treatment is with a VKA for 3 months over treatment for shorter periods (Grade 1A).
• For patients with an unprovoked DVT, the recommended treatment is with a VKA for at least 3 months (Grade 1A). The guidelines further recommend that all patients with unprovoked DVT be evaluated for the risk-to-benefit ratio of long-term therapy (Grade 1C). Long-term treatment is recommended for those patients who have a first unprovoked VTE that is a proximal DVT, do not have risk factors for bleeding, and can adhere to good anticoagulant monitoring (Grade 1A). Long-term treatment is also recommended for patients with a second episode of unprovoked DVT (Grade 2B).
• For patients with DVT and cancer, LMWH is recommended for the first 3–6 months of long-term anticoagulation (Grade 1A). Subsequent anticoagulant therapy with VKA or LMWH is recommended indefinitely or until the cancer has resolved (Grade 1C).
• In those patients who are receiving long-term anticoagulation therapy, the risk-to-benefit ratio of continuing treatment for the individual patient should be reassessed at periodic intervals (Grade 1C).
• In patients who are unexpectedly found to have an asymptomatic DVT, the same initial and long-term anticoagulation is recommended as that for comparable patients with a symptomatic DVT (Grade 1C).

Intensity of Anticoagulant Effect

• The guidelines recommend that the dose of VKA should be adjusted to maintain a target INR of 2.5 (range 2.0–3.0) for all durations of treatment (Grade 1A).
• The guidelines recommend against high-intensity VKA therapy (INR range 3.1–4.0) in comparison to an INR range of 2.0–3.0 (Grade 1A).

Treatment of Acute Ue DVT

Patients with acute UE DVT are recommended the same initial treatment with therapeutic doses of LMWH, UFH, or fondaparinux as described for lower extremity DVT. The recommendation is against the routine use of systemic or catheter-directed thrombolytic therapy for the majority of patients with acute UE DVT (Grade 1C). In select patients with acute UE DVT (recent onset of severe symptoms and a low risk of bleeding), the recommendations do suggest that CDT may be used for initial treatment if available expertise and resources are present (Grade 2C). The majority of patients with acute UE DVT are recommended against the routine use of surgical thrombectomy, transluminal angioplasty, catheter extraction, stent placement, staged approach to lysis followed by interventional or surgical procedure, or superior vena cava (SVC) filter placement (Grade 1C). However, in select patients (having a primary UE DVT, failing anticoagulant or thrombolytic treatment, and having severe persistent symptoms), the above interventions are recommended if available (Grade 2C). In patients with acute UE DVT, the placement of an SVC filter is suggested when anticoagulant treatment is contraindicated and clear evidence of DVT progression or clinically significant PE is present (Grade 2C). The recommended treatment for an acute UE DVT is VKA for ≥3 months (Grade 1C). For a UE DVT that is associated with an indwelling central venous catheter, the guidelines recommend against catheter removal if it is functional and an ongoing need for the catheter is present (Grade 2C). If a UE DVT is associated with an indwelling catheter that has been removed, the guidelines recommend against shortening the duration of long-term anticoagulant treatment to less than 3 months (Grade 2C).

Home versus in-Patient Treatment for DVT

A recent Cochrane review concluded home management is both cost-effective and preferred by patients.42 Six randomized controlled trials (RCTs) involving 1,708 patients compared home (LMWH) with hospital (LMWH or UFH) treatment for DVT. Patients treated at home with LMWH were less likely to have recurrence of VTE, and had lower mortality and fewer major bleeds. However, the home treatment patients were more likely to have minor bleeding than those treated in the hospital.

The PTS is a frequent complication of DVT. Patients complain of pain, swelling, heaviness, cramps, and itching or tingling of the affected leg. Ulcerations can occur. Standing and walking usually aggravate symptoms, whereas rest and elevation of the leg improve symptoms. Ipsilateral recurrent venous thrombosis is strongly associated with subsequent development of moderate or severe postthrombotic symptoms.43 Therefore, prevention of recurrent thrombi likely reduces PTS. Utilization of a properly fitted compression stocking at the time of diagnosis and continued for at least 2 years can be effective in the reduction of postthrombotic symptoms.44 Stockings that are fitted to the patient with a specific pressure gradient may be prescribed.

The grading system used in the ACCP Evidence-Based Clinical Practice Guidelines (8th Edition) are as follows: Grade 1 recommendations are strong, indicating the benefits do or do not outweigh risks, burden, and cost. Grade 2 recommendations are weaker and made when there is less certainty regarding the magnitude of the benefits, risks, burden, and cost. With a Grade 2 recommendation, individual patient values and preferences may become more important. An A, B, or C label is also given to all recommendations signifying the quality of evidence on which a given recommendation is based: A is the highest quality (e.g., multiple, well-designed RCTs with concordant results); B is of intermediate quality (e.g., one RCT or multiple trials without concordant results); and C is the lowest quality (e.g., small, observational study with significant potential for selection or reporting bias).45