Definition

The formation of a blood clot, most commonly in the deep veins of the leg, but sometimes also in the pelvis or upper extremities (the last discussed separately). In the legs, DVTs are either proximal (thigh) or distal (calf) vein thrombosis. Proximal DVTs are more associated with increased mortality and PE. The treatment of PE and DVT are usually identical, with the exception of PE causing severe hypoxia or hemodynamic instability. Pulmonary emboli are covered in depth in section Pulmonary: Pulmonary Embolism.

Etiology

DVT occurs in the presence of any of the three components of Virchow’s triad: hypercoagulability, stasis, or endothelial injury. DVT can be provoked by a strong trigger such as major surgery, trauma, immobility, cancer, OCP-use, nephrotic syndrome, and inflammatory conditions (e.g., SLE, IBD). Look for it in recent travelers, bedridden patients, patients with chronic indwelling lines, and those with history of prior clot or vascular injury. DVT can also be provoked by a combination of weak triggers, or entirely unprovoked.

Evaluation

• Patients may be risk stratified for DVT using criteria similar to those for PE (Wells’ score for DVT):
  • Give the patient one (1) point for each of the following (if present):
    • Active cancer or cancer treatment within 6 months.
    • Bedridden >3 days or recent surgery requiring general or regional anesthesia (within 12 weeks).
    • Paralysis or paresis.
    • Localized tenderness.
    • Entire leg swelling.
    • Asymmetric >3 cm calf swelling.
    • Pitting edema in symptomatic leg.
    • Collateral superficial veins (non-varicose).
    • Previously documented DVT.
  • Is there an alternative diagnosis (Baker’s cyst, superficial vein thrombosis, inguinal lymphadenoapthy, etc.) that is as likely as or more likely than DVT? If yes, subtract 2 points.
  • Score >3: high probability of DVT, prevalence of DVT 75%.
  • Score 1-2: moderate probability of DVT, prevalence of DVT 17%.
  • Score 0: low probability of DVT, prevalence of 3%.
• D-dimers: useful for ruling out DVT if your hospital has the very sensitive ELISA test. Some labs use the latex agglutination test, which is only 85-90% sensitive. The combination of negative D-dimers and a low probability of DVT obviates the need for further diagnostic testing, including ultrasound. D-dimers have low specificity and are frequently elevated in infection, cancer, systemic inflammation, surgery (within two months), renal disease, and cardiovascular disease, independent of clot. Therefore, D-dimer alone cannot diagnose VTE, and D-dimer elevation is very common in the hospitalized patient. 
• Duplex ultrasound: diagnosis includes lack of compressibility of a vein and abnormal Doppler flow.
• Hypercoagulability work-up: this may be considered in patients without a clear risk factor for DVT (unprovoked cases), young patients with weak provoking factors or strong family history, patients with recurrent DVT, or DVT in an unusual anatomical location.
  • Consider excluding medication-induced hypercoagulability before initiating an extensive work up. Common offenders include estrogen containing oral contraceptives or hormone replacement therapies and anticancer agents such as thalidomide or lenolidamide.
  • After the first event, the hypercoagulable work-up will lead to an etiology in only 30% of patients; after the second DVT only 50% will eventually have an etiology determined. Moreover, only 10-20% of people with an idiopathic DVT will ever have another event.
  • It is not recommended to begin the thrombophilia work up  at the time of the clot or while on anticoagulation: many tests are altered by either therapeutic anticoagulation or the presence of clot, the results won’t change acute management.
  • Choosing Wisely: don’t test for thrombophilia in adult patients with VTE in the setting of major transient risk factors (surgery, trauma, or prolonged immobility).
  • Guidelines for hypercoagulability work-up (if pursued):
    • Draw an extra blue top tube before starting heparin or warfarin if you suspect a hypercoagulable state: heparin will interfere with assays for antithrombin III and the lupus anticoagulant.
    • Protein C, S, anti-cardiolipin antibodies, prothrombin G20210A, and Factor V Leiden can be sent when patients are taking heparin. Note that Proteins C and S are vitamin K dependent factors and will be lowered by warfarin therapy.
    • AT III, Protein C, and Protein S may be transiently depressed during the acute event, and levels should generally not be assessed during this period.
    • Wait to send entire panel until two weeks after warfarin stopped, at least two days after DOAC stopped, and at least 24 hours after heparin stopped.
• Note that there is no consensus that all patients with unprovoked DVT/PE should have a hypercoagulability work-up. The most common defects are not associated with recurrent disease, and the ones that are, are uncommon. A targeted work-up is a more reasonable approach (see Connors et al NEJM 2017; 377:1177-1187).

Treatment

Typically involves unfractionated or low molecular weight heparin (e.g. enoxaparin) and warfarin or a direct oral anticoagulant (DOAC). Patients should be therapeutically anticoagulated as soon as possible. Thus, in most cases it is better to overshoot and risk bleeding than to undershoot and risk further embolic/thrombotic events. If using warfarin, start heparin and warfarin on day 1, and overlap for at least 5 days and until INR therapeutic. Dabigatran should be preceded by 5 days of heparin. Rivaroxaban and apixaban do not require concomitant parenteral anticoagulation. Duration of therapy is typically 3 months for provoked DVT, i.e. those where a cause can be readily identified. Indefinite anticoagulation may be considered for unprovoked DVT, particularly if associated with hemodynamically significant PE. This is because patients with an unprovoked VTE have a significantly increased risk of recurrence, as compared with patients who have provoked DVT. These patients have a 10% risk of recurrence in the first year after stopping anticoagulation and a cumulative risk of 40% at 5 years and more than 50% at 10 years. Choosing Wisely: don’t treat for more than 3 months in a person with a first VTE occurring in the setting of a major transient risk factor.

• Initial therapy: enoxaparin (1 mg/kg SQ q12h) plus warfarin (5 mg PO qnight). Continue enoxaparin until patient has received a minimum of five days of enoxaparin and has two consecutive INR >2 separated by 24 hours. Check PT/INR daily and adjust warfarin dose based on the results of these checks until a stable warfarin dose is achieved. Alternatively, consider initiation of a DOAC (see “DOACs”).
  • Dabigatran: 150mg PO BID after 5 days of UFH/LMWH.
  • Rivaroxaban: 15mg PO BID for 21 days, followed by 20mg daily.
  • Apixiban: 10mg BID for 7 days, then 5mg BID for 6 months.
• VTE + cancer: LMWH better than warfarin. Rivaroxaban and apixaban ok for non-GI cancers.
• Inpatient vs. outpatient care: clinically stable patients with DVT or PE may be considered for outpatient therapy at time of diagnosis if motivated and willing to have home self-injection and frequent follow-up.
• Consider hospitalization in patients with active peptic ulcer disease, bleeding in last 14 days, brain metastases, CVA in last 10 days, blindness, CNS or cord injury/surgery in last 10 days, family bleeding diathesis, patient weight <35 kg, platelets <80K or fall of >40%, if patient has had spinal or epidural anesthesia in past 3 days, or prior sensitivity to heparin or concomitant thrombolytic therapy. Careful attention must be paid to patients with reduced health literacy, including inability to maintain diary, inject medications, reliably follow medication schedules, recognize change in health status, or understand directions from home health team.
• Vena cava filters: the goal of a filter is to prevent embolization of DVTs into the lungs. Indications include active bleeding or a high risk of anticoagulant-associated bleeding. Lesser indications include PE despite appropriate anticoagulation or patients with massive PE and poor cardiopulmonary reserve. Studies have shown filters decrease incidence of pulmonary emboli. This benefit is offset by an increased recurrence rate of DVTs with permanent filter use and a lack of improved survival. Choosing Wisely: don’t use IVC filters routinely in patients with acute VTE. Retrievable filters are recommended over permanent filters when the risk for PE has resolved and/or when anticoagulation can be safely resumed.
• DVT prophylaxis should be addressed in all inpatients. Encourage early ambulation and order physical therapy when indicated. For those meeting criteria, initiate prophylaxis with low dose unfractionated heparin or low molecular weight heparin (e.g., enoxaparin). See section Medical Consultation: DVT/PE prophylaxis.

Key Points

• Patients should be risk stratified to assess the pre-test probability for DVT, just as they are for PE.
• In deciding whether or not to admit a patient for initiation of anticoagulation, consider the impact of acute pulmonary embolism on cardiac stability and oxygenation, as well as the patient’s ability to adhere to an anticoagulation regimen.
• It is essential to arrange close follow up as patients initiate anticoagulation.

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