Topic Editor: Grant E. Fraser, M.D., FRACGP, FACRRM, ASTEM
Review Date: 10/2/2012
Definition
Deep vein thrombosis (DVT) is a thrombus in the deep veins, most commonly in the lower extremities (thigh or leg) or pelvis. Other sites of DVT include neck, arm, chest or abdominal veins. Migration of thrombus from a deep vein to the pulmonary arteries results in pulmonary embolism, which is a potential life threat. Local long term complications include venous valvular dysfunction with secondary chronic limb edema.
Description
- DVT results from conditions which impair venous return, thus leading to endothelial injury or dysfunction, or causing hypercoagulability
- DVT is common in patients with prolonged bed rest, chronic debilitating disease, limb immobilization, inherited hypercoagulable states, or malignancy
- DVT may be asymptomatic or may have relatively rapid onset of pain and/or swelling of the affected limb
- It is common for the affected limb to have swelling, erythema, and tenderness
- Diagnosis is based on history, physical examination, risk factor analysis (Well's score), and duplex ultrasonography (rarely venogram)
- Some recommendations favor quantitative D-Dimer testing as an effective rule out of this diagnosis before performing duplex ultrasonography
- The major complications of DVT are pulmonary embolism (PE), and post-phlebitic syndrome
Epidemiology
Incidence/prevalence
- Incidence of venous thrombosis exceeds 0.1% annually. Each year, over 200,000 new cases occur in the U.S.
- Patients who have thromboembolism from a DVT have a 10-30% mortality by 30 days
- There is a 4-5 fold increased risk of thromboembolism in women during pregnancy and the postpartum period. The incidence of DVT during pregnancy and the postpartum period is approximately 1 case/1000 live births
Age
- DVT incidence increases with age from 2-3/100,000/year aged 20-30 years to 500/100,000/year aged 85 years or older
Gender
- Slight female predominance of DVT in those aged < 35 years
Risk factors
- Active malignancy, especially abdominal or pelvic, metastatic disease or recent chemotherapy
- Advanced age
- Antiphospholipid antibody (APLA) syndrome (autoimmune hypercoagulable state that causes thrombosis in both veins and arteries, and also leads to pregnancy related complications)
- Antithrombin deficiency
- Bechet's disease
- Central venous catheter/transvenous pacemaker
- Co-morbid conditions such as inflammation conditions, infection, or immobility
- Disability with immobility (such as severe congestive heart failure or chronic obstructive pulmonary disease)
- Elevated levels of coagulation factor VIIIc
- Exogenous estrogens
- Factor V Leiden carriers have increased risk of thrombosis
- HIV
- Hospitalized patients or nursing home residents
- Inflammatory bowel disease
- Lower extremity trauma
- Major surgery within prior 3 months
- Myeloproliferative diseases
- Myocardial infarction
- Obesity
- Neurologic disease with extremity paresis
- Pregnancy
- Previous history of proven DVT or PE
- Primary pulmonary hypertension
- Prior superficial vein thrombosis or varicose veins
- Protein C or S deficiency
- Prothrombin gene mutation G20210A
- Recent long distance travel
- Recent stroke or spinal cord injury
- Rheumatoid arthritis
- Sickle cell anemia
- Systemic lupus erythematosis
Etiology
The 3 important factors that alone or in combination lead to the majority of venous thrombosis are:
- Blood vessel injury
- Venous stasis
- Activation of the clotting system
The majority of patients with DVT have a triggering factor which leads to hypercoagulability (see risk factors) [e.g. cancer activating thrombin directly, infection directly over a deep vein, lower extremity trauma leading to vessel injury, or imbalance in the coagulation system such as genetic mutation in factor V or other members of the coagulation pathway]
History
- Patients with DVT commonly present with vague aches, erythema, tenderness along the distribution of the veins, and edema of the affected limb. However, these are nonspecific and vary in frequency and severity, with similar findings in both upper and lower extremity DVTs
- Patients may present with visible or palpable dilated collateral superficial veins
- Patients may present with low grade fever, especially in postoperative cases
- When pulmonary embolism occurs, symptoms can include shortness of breath, pleuritic chest pain, and in substantial PE hypotension, hypoxia, tachycardia and signs of right heart strain
Physical findings on examination
- Clinical diagnosis of DVT is inaccurate. Clinical prediction rules such as Wells prediction rules Wells Criteria (DVT)
can be used to establish pretest probability of DVT - Findings may include:
- Calf discomfort elicited by ankle dorsiflexion with the knee extended (Homan's sign); occasionally occurs with calf DVT; however, this sign is neither sensitive nor specific for DVT
- Calf swelling: If on measurement, the circumference of both legs below the tibial tuberosity have a difference of >3 cm, DVT is more likely
- Many DVT's present with phlegmasia cerulea dolens, which is a cold, tender, swollen and blue leg secondary to arterial insufficiency. This is caused by the swelling as a result of the DVT
- Increased skin temperature
- Palpable cord
- Swelling below knee in distal DVT and up to groin in proximal DVT
- Swelling with pitting edema of the affected extremity
Blood test findings
- Recommendations in a clinical practice guideline from the American Academy of Family Physicians and the American College of Physicians for the workup of patients with probable DVT:
- Use of validated clinical prediction rules to estimate the pretest probability of VTE and interpret test results (Wells prediction rule for DVT)
- Obtain a quantitative D-dimer in appropriately selected patients with low pretest probability of DVT. Negative results indicate a low likelihood of VTE; Positive results should receive a duplex ultrasonography of the symptomatic limb
- Ultrasonography (Doppler/Duplex) or venography recommended in patients with an intermediate to high pretest probability of lower-extremity DVT
- In provoked DVT (e.g. caused by a malignancy, immobilization, etc): There is generally little reason to perform a thrombophilia screen for inherited hypercoagulable states
- In unprovoked DVT (e.g. no good reason why the DVT happened): An evaluation for thrombophilia (underlying hypercoagulable state) is indicated. Potential items that can be tested include:
- Many centers have their own thrombophilia screening protocol. The most cost effective thrombophilia screen includes the following:
- Antiphospholipid antibodies
- Factor V Leiden mutation
- Homocysteine
- Prothrombin G20210A mutation
- In both provoked and unprovoked DVT, CBC, Comprehensive Panel, and if indicated B-HCG are reasonable laboratory testing. Additionally, in cases of liver disease, a baseline INR is indicated. Generally aPTT is obtained when IV non-fractionated heparin is used to treat DVT
Radiographic findings
- Imaging in deep venous thrombosis:
- Current first line imaging examination for DVT is duplex ultrasonography due to its relative ease of use, and high sensitivity and specificity
- Contrast venography is the gold standard for evaluation of DVT of the lower extremity, but is rarely if ever used
- Impedance plethysmography: As accurate as duplex ultrasound, less operator dependency, but poor at detecting venous thrombosis in the calf; not widely available
- MRI is the diagnostic test of choice for suspected iliac vein or inferior vena cava thrombosis when CT venography is contraindicated or technically inadequate. Current limitations are cost and lack of widespread availability
Other diagnostic test findings
- D-dimer testing: Indicated if the pretest probability of DVT is low (Wells score 2). Elevated levels are highly sensitive but non-specific. If D-dimer is normal, DVT is excluded in low-probability patients. In the case of elevated D-Dimer in a patient with a Wells score of
2, an ultrasound is indicated for further investigation
General treatment items
- Primary objective of treatment is to prevent pulmonary embolism (PE), reduce morbidity and prevent or minimize the risk of developing post-thrombotic syndrome (PTS). In cases of phlegmasia cerulea dolens, obtaining IV access, apply low flow oxygen, and obtain surgical or vascular consult
- General supportive measures include pain control with analgesics other than aspirin and NSAIDs (because of their anti-platelet effects) and, during periods of inactivity, the legs should be elevated, with the support of a pillow or similar device to avoid venous compression
- Acute Treatment:
- Low-Molecular-Weight Heparin (LMWH), such as enoxaparin, is the initial treatment of choice. The patient remains on LWMH for at least 5 days and until the INR is therapeutic (2.0-3.0) for at least 2 days in a row. Warfarin is usually started the evening of the diagnosis being made and always after LWMH has already been initiated (warfarin can cause a hypercoagulable state)
- IV non-fractionated heparin can also be utilized; but generally is only used in patients who might need a procedure (such that the heparin can be shut off)
- Warfarin therapy should be initiated when appropriate (usually within 72 hours of initiation of heparin or LMWH). A 5 mg daily dose is recommended in most patients. Higher doses tend to create a hypercoagulable state due to a precipitous decrease in protein C during the first 36 hours of warfarin therapy, and tend to result in more erratic changes in the INR
- Long-term LMWH may be preferable to warfarin in patients with cancer or those whose INR is difficult to stabilize
- Oral Direct Thrombin Inhibitors (DTI's): Dabigatran (Pradaxa) and Rivaroxaban (Xarelto) are DTIs which are effective for treatment of DVT without need for LMWH or Warfarin. FDA approval is likely forthcoming for rivaroxaban for this indication. The advantage is a single oral agent without need for injectable agents or blood test based monitoring of therapy
- Outpatient DVT treatment is recommended in patients without prior DVT, thrombophilia, or substantial comorbidity, but not for those who are pregnant or unlikely to adhere to therapy. In cases of very large proximal DVT, especially involving the iliac veins or IVC, admission is indicated, as embolism would likely be rapidly fatal without intervention
- Exclusions from outpatient treatment of DVT include patients who are at higher risk of complications (e.g., hemoglobin 7 g/dL, platelet count 75,000, guaiac-positive stool, recent cerebrovascular accident or noncutaneous surgery, noncompliance)
- Compression stockings are effective in reducing the incidence of post thrombotic syndrome and should be used within 1 month of proximal DVT and for at least 1 year after diagnosis
- Insertion of an inferior vena cava filter is indicated, to prevent pulmonary embolism, in patients who have contraindications to anticoagulation or who have a thromboembolic event while on adequate anticoagulation
- Thrombolytic therapy (alteplase, streptokinase, reteplase, tenecteplase) is not FDA approved, but has been used in patients with extensive iliofemoral DVT who are at a low bleeding risk
- Thrombectomy is occasionally recommended for patients with extensive disease, in consultation with a vascular surgeon
- Chronic Treatment:
- Warfarin is an effective long term therapy, with INR goal of 2.0-3.0 preventing further DVTs in most cases
- The reason why the DVT occurred, and the patient's risk factors determines optimal duration of anticoagulant therapy
- Therapy for 3 to 6 months is generally satisfactory in patients with reversible risk factors (low-risk group)
- A high D-dimer level measured after 3 months of anticoagulation therapy in patients with unprovoked DVT should favor a longer duration of therapy
- Anticoagulation for at least 6 months is recommended for patients with DVT of unclear cause, or with medical risk factors for DVT (intermediate-risk group)
- Lifelong anticoagulation is indicated in patients who have DVT and active cancer, and in patients with thrombophilia [e.g., protein C or S deficiency, antiphospholipid antibody, factor V leiden, and others; and those with recurrent episodes of idiopathic DVT (high-risk group)]
Medications indicated with specific doses
Antithrombotics
- Dalteparin
- Enoxaparin
- Fondaparinux
- Heparin
- Rivaroxaban
- Tinzaparin
- Warfarin
Dietary or Activity restrictions
- Patients taking warfarin must be aware that foods high in vitamin K can affect INR
Disposition
Admission Criteria
- Ileofemoral or IVC thrombus
- Patients with concomitant PE or other significant co-morbitidities
- Patients unable to receive LMWH as an outpatient
- Patient's unlikely or unable to follow the treatment plan
- Patients with high bleeding risk
- Patients with phlegmasia
- Pregnancy
- Severe Anemia (Hb7.0)
- Thrombocytopenia
Discharge Criteria - Outpatient therapy with LMWH:
- No serious concomitant disease that needs hospitalization
- Family member or patient is willing and trained to inject the medication
- Note that heparin-induced thrombocytopenia, although less common with LMWH, can still occur
- Patients with distal or superficial thrombophlebitis can be discharged with close follow up
