Deep venous thrombosis (DVT) is a condition in which a deep vein – most commonly in the lower limb, but can also affect the upper limbs – has it`s flow obstructed by a blood clot. It is caused due to a dysfunction in factors that affect the coagulation, particularly the Virchow`s triad. The Virchow`s triad is composed by:
Vascular endothelial injury
Many situations can predispose an individual to DVT:
Hospital admission (previous or current)
IV drug use
Medications (oral contraceptives, hormone replacement therapy, tamoxifen, glucocorticoids).
Nephropathies (CKD, nephrotic syndrome)
Inflammatory bowel disease
Paroxysmal nocturnal hemoglobinuria
Superficial vein thrombosis
Hypercoagulable states (Factor V Leiden, Prothrombin G20210A mutation, S or C protein deficiencis, AT-III deficiency)
The term venous thromboembolism (VTE) includes DVT and pulmonary embolism (PE). PE is a serious condition and it will be discussed in a different moment.
CLINICAL FEATURES OF DVT:
Depending on the affected veins, lower extremity DVT can be classified as distal (calf) or proximal (popliteal, femoral or iliac). Most cases of DVT that cause PE (90%) are proximal.
Physical examination in lower extremity DVT may reveal edema, dilated superficial veins, pain and warm skin. Patients with phlegmasia may have in addition to the edema reduction in pulses and changes in the color of the limb (blanching).
Upper extremity DVT presents as severe and sudden arm swelling.
If pulmonary embolism (PE) develops, patients may present with shortness of breath, tachycardia, tachypnea, chest pain, lightheadedness, syncope or cardiac arrest.
In addition to the history and physical examination, many tools can be used to help in the diagnosis of DVT. Contrast venography and magnet resonance venography are very good for diagnosing, but are invasive (regular contrast venography) and not readily available (MR venography). Since these tests are not readily available in a practical manner, an approach that takes in consideration the pretest probability PLUS additional exams (D-Dimer, duplex ultrasound or plethysmography) becomes a good way to diagnose DVT.
The pretest probability can be calculated using the Wells score for DVT:
|Active cancer (Treatment or palliation within 6 months)||1|
|Bedridden recently >3 days or major surgery within four weeks||1|
|Calf swelling >3 cm compared to the other leg|
Measured 10cm below tibial tuberosity
|Collateral (nonvaricose) superficial veins present||1|
|Paralysis, paresis, or recent plaster immobilization of the lower extremity||1|
|Entire leg swollen||1|
|Localized tenderness along the deep venous system||1|
|Pitting edema, confined to symptomatic leg||1|
|Previously documented DVT||1|
|Alternative diagnosis to DVT as likely or more likely||-2|
|Result||Score (Add points)|
|High probability||3 or more|
|Low probability||0 or less|
The modified Wells score adds an extra feature: previously documented DVT (+1 point). In the modified score, DVT is likely if the score is 2 or greater and unlikely if it is 1 or less.
Patients with low pretest probability should have the D-dimer measured. If they have low pretest probability and normal D-dimer (<500 mg/mL) they may not need further testing since they are not likely to have DVT (negative D-dimer and low pretest probability has high negative predictive value).
Patients with intermediate or high pretest probability (likely DVT) should be evaluated by compression ultrasonography, which is the noninvasive method of choice. In rare cases in which USG is not available, plethysmography may be an alternative.
In cases which the noninvasive test is negative but the clinical suspicion is high, another noninvasive test can be repeated in 5-7 days. If the results are dubious, venography is indicated.
After diagnosis is established, every patient with DVT should have at least some tests ordered: CBC, coagulation studies, CMP, liver function tests, urinalysis ESR. Other tests such as imaging studies and occult blood on stools may be needed if a particular condition is suspected (such as malignancy).
In general, patients should not be screened for hereditary disorders in their first episode of VTE. An exception can be made for patients with a family history of a first degree relative with VTE – these patients should be screened for inherited hypercoagulable states (protein C and S deficiencies, favor V Leiden, AT-III deficiency and prothrombin gene mutation). Patients with recurrent thrombosis or thrombosis of unusual veins (visceral veins) should be tested for the inherited disorders mentioned plus antiphospholipid syndrome and malignancy.
Initial treatment of lower extremity DVT with anticoagulation should be started as soon as possible. Different agents may be used for anticoagulation such as unfractioned heparin, low molecular weight heparin, fondaparinux or modern oral anticoagulants. Warfarin cannot be started as monotherapy right at the beginning, it must be used (if at all) together with a different anticoagulant for the first 3-5 days.
Doses for Treatment:
Enoxaparin (LOVENOX): 1mg/kg/dose SC q12hr OR 1.5mg/kg/day.
Fondaparinux (ARIXTRA): <50kg – 5mg SC qDay; 50 to 100kg – 7.5mg qDay; >100kg 10mg qDay.
Warfarin: Start with 2 to 5mg qDay and monitor INR, adjusting accordingly (target INR 2-3).
Rivaroxaban (XARELTO): 15mg PO BID with food for 21 days followed by 20mg qDay with food.
Apixaban (ELIQUIS): 10mg PO BID for 7 days. After that 5mg BID.
Dabigatran (PRADAXA): 150mg PO BID (after 5-10 days of therapy with a parenteral anticoagulant)
Edoxaban (SAVAYSA): > 60kg – 60mg PO qDay (after 5-10 days of therapy with a parenteral anticoagulant). <60kg -30mg PO qDay.
Anticoagulation should be maintained usually for 3 months. It may be extended indefinitely in particular cases (very high risk patients, unprovoked proximal DVT, recurrent DVTs or PEs).
Some patients may have contraindication to anticoagulation (active bleeding, platelets <50.000/microL, high-risk bleeding procedure recent or planned, major trauma, history of intracranial hemorrhage). These patients can receive an inferior vena cava filter (IVC filter). However, after (and if) the contraindication is resolved, even individuals with the IVC filter should receive anticoagulation. IVC filter may also play a role in patients with recurring events despite anticoagulation, or patients with comorbidities that would make a PE even harder to tolerate (cardiopulmonary diseases for instance).
Patients with massive iliofemoral DVTs or phlegmasia cerulea dolens may need aggressive intervention due to the risk of gangrene. Thrombectomy (by catheter or surgical) or thrombolytics (by catheter or systemic) may be considered for these patients.
In patients with limited distal DVTs observation with weekly ultrasounds may be an acceptable choice. If the lesion starts to extend towards proximal veins anticoagulation should be started.
A great number of patients (20-80%) may develop post-thrombotic syndrome after DVT. This syndrome is characterized by chronic venous insufficiency that can manifest with edema, pain, pigmentation, skin changes or ulcers. Management is similar to other causes of chronic venous disease and include limb elevation, compression therapy, exercise, and medication (horse chestnut seed extract HCE/Escin 300mg (=50mg of escin)) if needed. Aspirin therapy (300mg/day) may help in the healing of venous ulcers. Surgical intervention (traditional or endovascular) may be beneficial for some patients with obstruction or reflux.
Regarding upper extremity DVT, if it presents with mild symptoms it may be treated with anticoagulation for at least three months. In those with moderate to severe symptoms catheter-directed alteplase can be used. Patients with primary upper extremity DVT may benefit from surgery (thoracic outlet decompression or first rib resection) since the thoracic outlet obstruction is a common cause of spontaneous upper extremity DVT. Surgery should be conducted in the same admission if possible. Even after thrombolytics and surgery, upper extremity DVT should be anticoagulated for at least three months.
SOURCES & FURTHER READING:
- Streiff MB et al. Guidance for the treatment of deep vein thrombosis and pulmonary embolism. J Thromb Thrombolysis. 2016; 41: 32–67.
- Damlo S. AAFP and ACP Publish Recommendations on Diagnosis and Management of VTE. Am Fam Physician. 2007 Oct 15;76(8):1225-1229.
- Hirsh J, Hoak J. Management of Deep Vein Thrombosis and Pulmonary Embolism. Circulation. 1996;93:2212-2245.
- Kearon C et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-352. doi:10.1016/j.chest.2015.11.026.
- Heit JA et al. Risk Factors for Deep Vein Thrombosis and Pulmonary EmbolismA Population-Based Case-Control Study. Arch Intern Med. 2000;160(6):809-815. doi:10.1001/archinte.160.6.809.
- Subramaniam RM et al. Diagnosis of lower limb deep venous thrombosis in emergency department patients: performance of Hamilton and modified Wells scores. Ann Emerg Med. 2006;48(6):678.
- Kearon C, Akl EA. Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood 2014 123:1794-1801; doi: https://doi.org/10.1182/blood-2013-12-512681