DVT occurs most commonly in the lower extremities or pelvis (see figure Deep veins of the legs Deep veins of the legs Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more ). It can also develop in deep veins of the upper extremities (4 to 13% of DVT cases).
Deep veins of the legs
Lower extremity DVT is much more likely to cause pulmonary embolism Pulmonary Embolism (PE) Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more (PE), possibly because of the higher clot burden. The superficial femoral and popliteal veins in the thighs and the posterior tibial and peroneal veins in the calves are most commonly affected. Calf vein DVT is less likely to be a source of large emboli but can propagate to the proximal thigh veins and from there cause PE. About 50% of patients with DVT have occult PE, and at least 30% of patients with PE have demonstrable DVT.
Pearls & Pitfalls
Etiology of DVT
Many factors can contribute to DVT (see table Risk Factors for Venous Thrombosis Risk Factors for Venous Thrombosis Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more ). Cancer is a risk factor for DVT, particularly in older patients and in patients with recurrent thrombosis. The association is strongest for mucin-secreting endothelial cell tumors such as bowel or pancreatic cancers. Occult cancers may be present in patients with apparently idiopathic DVT, but extensive workup of patients for tumors is not recommended unless patients have major risk factors for cancer or symptoms suggestive of an occult cancer.
Pathophysiology of DVT
Lower extremity DVT most often results from
Impaired venous return (eg, in immobilized patients)
Endothelial injury or dysfunction (eg, after leg fractures)
Upper extremity DVT most often results from
Endothelial injury due to central venous catheters, pacemakers, or injection drug use
Upper extremity DVT occasionally occurs as part of superior vena cava (SVC) syndrome (compression or invasion of the superior vena cava by a tumor and causing symptoms such as facial swelling, dilated neck veins, and facial flushing) or results from a hypercoagulable state or subclavian vein compression at the thoracic outlet. The compression may be due to a normal or an accessory first rib or fibrous band (thoracic outlet syndrome Thoracic Outlet Compression Syndromes (TOS) Thoracic outlet compression syndromes are a group of poorly defined disorders characterized by pain and paresthesias in a hand, the neck, a shoulder, or an arm. They appear to involve compression... read more ) or occur during strenuous arm activity (effort thrombosis, or Paget-Schroetter syndrome, which accounts for 1 to 4% of upper extremity DVT cases).
Deep venous thrombosis usually begins in venous valve cusps. Thrombi consist of thrombin, fibrin, and red blood cells with relatively few platelets (red thrombi); without treatment, thrombi may propagate proximally or travel to the lungs.
Common complications of deep venous thrombosis include
Much less commonly, acute DVT leads to phlegmasia alba dolens or phlegmasia cerulea dolens, both of which, unless promptly diagnosed and treated, can result in venous gangrene.
In phlegmasia alba dolens, a rare complication of DVT during pregnancy, the leg turns milky white. Pathophysiology is unclear, but edema may increase soft-tissue pressure beyond capillary perfusion pressures, resulting in tissue ischemia and wet gangrene.
In phlegmasia cerulea dolens, massive iliofemoral venous thrombosis causes near-total venous occlusion; the leg becomes ischemic, extremely painful, and cyanotic. Pathophysiology may involve complete stasis of venous and arterial blood flow in the lower extremity because venous return is occluded or massive edema cuts off arterial blood flow. Venous gangrene may result.
Infection rarely develops in venous clots. Jugular vein suppurative thrombophlebitis (Lemierre syndrome), a bacterial (usually anaerobic) infection of the internal jugular vein and surrounding soft tissues, may follow tonsillopharyngitis and is often complicated by bacteremia and sepsis. In septic pelvic thrombophlebitis, pelvic thromboses develop postpartum and become infected, causing intermittent fever. Suppurative (septic) thrombophlebitis, a bacterial infection of a superficial peripheral vein, comprises infection and clotting that usually is caused by venous catheterization.
Symptoms and Signs of DVT
DVT may occur in ambulatory patients or as a complication of surgery or major medical illness. Among high-risk hospitalized patients, most deep vein thrombi occur in the small calf veins, are asymptomatic, and may not be detected.
When present, symptoms and signs of DVT (eg, vague aching pain, tenderness along the distribution of the veins, edema, erythema) are nonspecific, vary in frequency and severity, and are similar in arms and legs. Dilated collateral superficial veins may become visible or palpable. Calf discomfort elicited by ankle dorsiflexion with the knee extended (Homans sign) occasionally occurs with distal leg DVT but is neither sensitive nor specific. Tenderness, swelling of the whole leg, > 3 cm difference in circumference between calves, pitting edema, and collateral superficial veins may be most specific; DVT is likely with a combination of ≥ 3 in the absence of another likely diagnosis (see table Probability of Deep Venous Thrombosis Probability of Deep Venous Thrombosis Based on Clinical Factors Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more ).
Low-grade fever may be present; DVT may be the cause of fever without an obvious source, especially in postoperative patients. Symptoms of pulmonary embolism Symptoms and Signs Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more , if it occurs, may include shortness of breath and pleuritic chest pain.
Common causes of asymmetric leg swelling that mimic DVT are
Obstruction of a pelvic vein
Obstruction of a lymphatic vessel in the pelvis
Popliteal bursitis (Baker cyst) that obstructs venous return
Less common causes include
Abdominal or pelvic tumors that obstruct venous or lymphatic return
Symmetric bilateral leg swelling is the typical result of use of drugs that cause dependent edema (eg, dihydropyridine calcium channel blockers, estrogen, high-dose opioids), venous hypertension (usually due to right heart failure), and hypoalbuminemia; however, such swelling may be asymmetric if venous insufficiency coexists and is worse in one leg.
Common causes of calf pain that mimic acute DVT include
Venous insufficiency and postphlebitic syndrome Chronic Venous Insufficiency and Postphlebitic Syndrome Chronic venous insufficiency is impaired venous return, sometimes causing lower extremity discomfort, edema, and skin changes. Postphlebitic (postthrombotic) syndrome is symptomatic chronic... read more
Ruptured popliteal (Baker) cyst (pseudo-DVT), which causes calf swelling, pain, and sometimes bruising in the region of the medial malleolus
Partial or complete tears of the calf muscles or tendons
Diagnosis of DVT
Sometimes D-dimer testing
History and physical examination help determine probability of DVT before testing (see table Probability of Deep Venous Thrombosis Probability of Deep Venous Thrombosis Based on Clinical Factors Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more ). Diagnosis is typically by ultrasonography with Doppler flow studies (duplex ultrasonography). The need for additional tests (eg, D-dimer testing) and their choice and sequence depend on pretest probability and sometimes ultrasonography results. No single testing protocol is best; one approach is described in the figure One Approach to testing for suspected DVT One approach to testing for suspected deep venous thrombosis Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more .
One approach to testing for suspected deep venous thrombosis
Ultrasonography identifies thrombi by directly visualizing the venous lining and by demonstrating abnormal vein compressibility or, with Doppler flow studies, impaired venous flow. The test is > 90% sensitive and > 95% specific for femoral and popliteal vein thrombosis but is less accurate for iliac or calf vein thrombosis.
D-Dimer is a byproduct of fibrinolysis; elevated levels suggest recent presence and lysis of thrombi. D-Dimer assays vary in sensitivity and specificity; however, most are sensitive and not specific. Only the most accurate tests should be used. For example, a highly sensitive test is enzyme-linked immunosorbent assay (ELISA), which has a sensitivity of about 95%.
If pretest probability of DVT is low, DVT can be safely excluded in patients with a normal D-dimer level on a sensitive test. Thus, a negative D-dimer test can identify patients who have a low probability of DVT and do not require ultrasonography. However, a positive test result is nonspecific; because levels can be elevated by other conditions (eg, liver disease, trauma, pregnancy, positive rheumatoid factor, inflammation, recent surgery, cancer), further testing is necessary.
If pretest probability of DVT is moderate or high, D-dimer testing can be done at the same time as duplex ultrasonography. A positive ultrasound result confirms the diagnosis regardless of the D-dimer level. If ultrasonography does not reveal evidence of DVT, a normal D-dimer level helps exclude DVT. Patients with an elevated D-dimer level should have repeat ultrasonography in a few days or additional imaging, such as venography, depending on clinical suspicion.
Contrast venography was the definitive test for the diagnosis of DVT but has been largely replaced by ultrasonography, which is noninvasive, more readily available, and almost equally accurate for detecting DVT. Venography may be indicated when ultrasonography results are normal but pretest suspicion for DVT is high. The complication rate is 2%, mostly because of contrast agent allergy.
Noninvasive alternatives to contrast venography are being studied. They include MRI venography using an intravenous contrast agent and direct MRI of thrombi using T1-weighted gradient-echo sequencing and a water-excitation radiofrequency pulse; theoretically, the latter test can provide simultaneous views of thrombi in deep veins and subsegmental pulmonary arteries (for diagnosis of pulmonary embolism).
If symptoms and signs suggest PE, additional imaging (eg, CT pulmonary angiography or, less often, ventilation/perfusion [V/Q] scanning) is required.
Determination of cause
Patients with confirmed DVT and an obvious cause (eg, immobilization, surgical procedure, leg trauma) need no further testing. Testing to detect hypercoagulability Diagnosis In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces. Numerous genetic, acquired, and environmental factors can tip... read more is controversial but is sometimes done in patients who have idiopathic (or unprovoked) DVT or recurrent DVT, in patients who have a personal or family history of other thromboses, and in young patients with no obvious predisposing factors. Some evidence suggests that presence of hypercoagulability does not predict DVT recurrence as well as clinical risk factors.
Screening patients with DVT for cancer has a low yield. Selective testing guided by complete history and physical examination and basic "routine" tests (complete blood count, chest x-ray, urinalysis, liver enzymes, and serum electrolytes, blood urea nitrogen [BUN], creatinine) aimed at detecting cancer is probably adequate. In addition, patients should have any age- and gender-appropriate cancer screening (eg, mammography, colonoscopy) that is due.
Prognosis for DVT
Without adequate treatment, lower extremity DVT has a 3% risk of fatal PE; death due to upper extremity DVT is very rare. Risk of recurrent DVT is lowest for patients with transient risk factors (eg, surgery, trauma, temporary immobility) and greatest for patients with persistent risk factors (eg, cancer), idiopathic DVT, or incomplete resolution of past DVT (residual thrombus). A normal D-dimer level obtained after warfarin is stopped may help predict a relatively low risk of DVT or PE recurrence. Risk of venous insufficiency is difficult to predict. Risk factors for postphlebitic syndrome include proximal thrombosis, recurrent ipsilateral DVT, and body mass index (BMI) ≥ 22 kg/m2.
Treatment of DVT
Sometimes inferior vena cava filter, thrombolytic drugs, or surgery
Treatment is aimed primarily at PE prevention Prevention Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more and secondarily at symptom relief and prevention of DVT recurrence, chronic venous insufficiency Chronic Venous Insufficiency and Postphlebitic Syndrome Chronic venous insufficiency is impaired venous return, sometimes causing lower extremity discomfort, edema, and skin changes. Postphlebitic (postthrombotic) syndrome is symptomatic chronic... read more , and postphlebitic syndrome. Treatment of lower and upper extremity DVT is generally the same.
General supportive measures include pain control with analgesics, which may include short (3- to 5-day) courses of a nonsteroidal anti-inflammatory drug (NSAID). Extended treatment with NSAIDs and aspirin should be avoided because their antiplatelet effects may increase the risk of bleeding complications. In addition, elevation of legs (supported by a pillow or other soft surface to avoid venous compression) is recommended during periods of inactivity. Patients may be as physically active as they can tolerate; there is no evidence that early activity increases risk of clot dislodgement and PE and may help to reduce the risk of the postphlebitic syndrome (1 Treatment reference Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more ).
(For details on drugs and their complications, see Drugs for Deep Venous Thrombosis Drugs for Deep Venous Thrombosis All patients with deep venous thrombosis (DVT) are given anticoagulants and in rare cases thrombolytics. A number of anticoagulants are effective for management of deep venous thrombosis (see... read more )
All patients with DVT are given anticoagulants. Typically, patients are initially given an injectable heparin (unfractionated or low molecular weight) for 5 to 7 days, followed by longer term treatment with an oral drug. For patients who are to start warfarin, warfarin is started within 24 to 48 hours after the start of the injectable heparin. For patients who are to start an oral factor Xa inhibitor (edoxaban) or dabigatran etexilate, the oral agent is started on the day after the 5 to 7 days of injectable heparin is completed. The reason for this different approach is that when starting warfarin, it takes about 5 days to attain a therapeutic effect; hence, the need to overlap with rapidly acting heparin for 5 to 7 days. On the other hand, oral factor Xa inhibitors and dabigatran attain a therapeutic effect within 2 to 3 hours of intake and there is no need to overlap these drugs with an injectable heparin. Select patients may continue treatment with a low-molecular-weight heparin rather than switching to an oral drug, eg, patients with extensive iliofemoral DVT or selected patients with cancer. Alternatively, anticoagulation may be initiated with selected direct oral anticoagulants (rivaroxaban or apixaban) without first giving an injectable heparin; however, use of these drugs may be limited due to higher cost compared to warfarin. (See also the American College of Chest Physicians recommendation, Antithrombotic Therapy for VTE Disease.)
Inadequate anticoagulation in the first 24 to 48 hours may increase risk of recurrence or PE. Acute DVT can be treated on an outpatient basis unless severe symptoms require parenteral analgesics, other disorders preclude safe outpatient discharge, or other factors (eg, functional, socioeconomic) might prevent the patient from adhering to prescribed treatments.
Inferior vena cava (IVC) filter
An IVC filter may help prevent pulmonary embolism in patients with lower extremity DVT who have contraindications to anticoagulant therapy or in patients with recurrent DVT (or emboli) despite adequate anticoagulation. An IVC filter is placed in the inferior vena cava just below the renal veins via catheterization of an internal jugular or femoral vein. Some IVC filters are removable and can be used temporarily (eg, until contraindications to anticoagulation subside or resolve).
IVC filters reduce risk of acute embolic complications but can have longer-term complications (venous collaterals can develop, providing a pathway for emboli to circumvent the filter, and there is also an increased risk of recurrent DVT). Also, IVC filters can dislodge or become obstructed by a clot. Thus, patients with recurrent DVT or nonmodifiable risk factors for DVT may still require anticoagulation despite the presence of an IVC filter. A clotted filter may cause bilateral lower extremity venous congestion (including acute phlegmasia cerulea dolens), lower body ischemia, and acute kidney injury Acute Kidney Injury (AKI) Acute kidney injury is a rapid decrease in renal function over days to weeks, causing an accumulation of nitrogenous products in the blood (azotemia) with or without reduction in amount of urine... read more . Treatment for a dislodged filter is removal, using angiographic or, if necessary, surgical methods. Despite widespread use of IVC filters, efficacy in preventing PE is understudied and unproved. IVC filters should be removed whenever possible.
Thrombolytic (fibrinolytic) drugs
Thrombolytic drugs, which include alteplase, tenecteplase, and streptokinase, lyse clots and may be more effective than anticoagulation alone in selected patients, but the risk of bleeding is higher than with heparin. Consequently, thrombolytics should be considered only in highly selected patients with DVT. Patients who may benefit from thrombolytics include those < 60 years with extensive iliofemoral DVT who have evolving or existing limb ischemia (eg, phlegmasia cerulea dolens) and do not have risk factors for bleeding.
Surgery is rarely needed. However, thrombectomy, fasciotomy, or both are mandatory for phlegmasia alba dolens or phlegmasia cerulea dolens unresponsive to thrombolytics to try to prevent limb-threatening gangrene.
Prevention of DVT
It is preferable and safer to prevent DVT than to treat it, particularly in high-risk patients. The following modalities are used (for a more complete discussion, see DVT Prevention Deep Venous Thrombosis (DVT) Prevention It is preferable and safer to prevent deep venous thrombosis (DVT) than to treat it, particularly in high-risk patients. DVT prophylaxis begins with risk assessment. Risk, along with other factors... read more ).
Prevention of immobility
Anticoagulation (eg, low molecular weight heparin, fondaparinux, adjusted-dose warfarin, direct oral anticoagulant)
Intermittent pneumatic compression
Inferior vena cava (IVC) filters Inferior vena cava (IVC) filter Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more do not prevent DVT but are sometimes placed in an attempt to prevent pulmonary embolism (PE). An IVC filter may help prevent PE in patients with lower extremity DVT who have contraindications to anticoagulant therapy or in patients with recurrent DVT (or emboli) despite adequate anticoagulation. IVC filters are sometimes used in situations where efficacy is not proven, for example, for the primary prevention of PE in patients after certain types of surgery or in patients with multiple severe injuries.
Symptoms and signs are nonspecific, so clinicians must be alert, particularly in high-risk patients.
Low-risk patients may have D-dimer testing, as a normal result essentially excludes deep venous thrombosis (DVT); others should have ultrasonography.
Treatment initially is with an injectable heparin (unfractionated or low molecular weight heparin [LMWH]) followed by an oral anticoagulant (warfarin, dabigatran, or a factor Xa inhibitor) or perhaps a LMWH; alternatively, the oral factor Xa inhibitors rivaroxaban and apixaban may be used for initial and ongoing treatment.
Duration of treatment is typically 3 or 6 months, depending on the presence and nature of risk factors; certain patients require lifelong treatment.
Preventive treatment is required for bedbound patients with major illness and/or those undergoing certain surgical procedures.
Early mobilization, leg elevation, and an anticoagulant are the recommended preventive measures; patients who should not receive anticoagulants may benefit from intermittent pneumatic compression devices, elastic stockings, or both.