a. The main goals of treatment for DVT include relief of symptoms and prevention of PE, CTPH, PTS, and recurrent VTE. Once the diagnosis of DVT is confirmed, anticoagulation should be started immediately unless there is a contraindication. Initial therapy should include heparin, low-molecularweight heparin (LMWH), or fondaparinux followed by an oral anticoagulant (vitamin K antagonist or VKA). LMWH and fondaparinux are renally cleared, and although the LMWHs can be given in patients with renal insufficiency after dose adjustment, both are contraindicated in patients requiring dialysis.

Weight-based dosing of unfractionated heparin (UFH) (80 U/kg bolus followed by 18 U/kg/h intravenous [IV] infusion) has been shown to achieve a therapeutic activated partial thromboplastin time (aPTT) more rapidly than fixed-dose regimens. The target aPTT has traditionally been 1.5 to 2.5 times the control aPTT; however, the actual therapeutic aPTT range varies among laboratories because of their use of different aPTT reagents. The American College of Chest Physicians (ACCP) and the College of American Pathologists now advocate the use of an anti-factor Xa assay to establish a heparin dose-response curve for the aPTT ratio (of each laboratory), using concentrations that correlate to therapeutic heparin levels of 0.3 to 0.7 IU/mL determined by factor Xa inhibition. The aPTT should not be followed in patients with an abnormal baseline aPTT (e.g., in patients with lupus anticoagulant) and in patients who require unusually high doses of heparin such as in AT deficiency. In these situations, the anti-factor Xa assay should be used. UFH can also be administered subcutaneously as an alternative to IV administration, and several dosing nomograms have been recommended. One approach is to give an initial IV bolus of 5,000 U followed by a subcutaneous dose of 17,500 U twice daily on the first day. Blood for an aPTT is drawn 6 hours after
the initiation dose, and subsequent doses are adjusted accordingly to achieve an aPTT 1.5 to 2.5 times the control. Another fixed-dose nomogram recommends a subcutaneous loading dose of 333 U/kg followed by fixed doses of 250 U/kg subcutaneously every 12 hours without the need for aPTT monitoring.

LMWH is administered as a weight-based subcutaneous injection. Enoxaparin, the most commonly used agent in the United States, is given either as a once-daily injection (1.5 mg/kg/d) or twice per day (1 mg/kg every 12 hours). No monitoring is required except in obese, pediatric, or pregnant patients or patients with renal insufficiency. The anti-Xa level using LMWH as a reference standard should be measured 4 hours after an injection. The therapeutic range is 0.5 to 1.0 IU/mL for the 12-hour regimen and ≥ 1.0 IU/mL for the daily dose.

Once anticoagulation with UFH or LMWH is begun, a VKA may be initiated. The overlap should be continued for a minimum of 4 to 5 days and until the international normalized ratio (INR) is within the target range of 2.0 to 3.0 for two consecutive days to permit adequate depletion of vitamin K-dependent coagulation factors.

Fondaparinux, an indirect factor Xa inhibitor, is approved by the US Food and Drug Administration (FDA) for use as DVT prophylaxis in patients undergoing orthopedic procedures (total hip and knee arthroplasty) and abdominal surgery. It is also approved as treatment for acute DVT and PE when used in combination with a VKA. Its efficacy and safety in comparison with LMWH for the treatment of acute DVT and in comparison with IV UFH for the treatment of PE have been shown in large randomized controlled trials. Fondaparinux is administered as a once-daily subcutaneous injection of 2.5 mg for DVT prophylaxis and 5, 7.5, or 10 mg based on body weight (< 50, 50 to 100, and > 100 kg, respectively) for the treatment of DVT or PE. Fondaparinux is contraindicated in patients with severe renal impairment (creatinine clearance < 30 mL/min) and bacterial endocarditis. When used as DVT prophylaxis, fondaparinux is also contraindicated in patients with body weight < 50 kg who are undergoing hip fracture, hip replacement or knee replacement surgery, and abdominal surgery

Thrombolytic therapy for DVT may be beneficial in select individuals and is preferably administered locally via a catheter-directed approach. Systemic lysis is also an option if a catheter-directed approach is not available. Both routes carry an increased risk of systemic hemorrhage compared with standard anticoagulation alone. Although it has been suggested that the use of thrombolytics promotes early recanalization and minimizes the incidence of PTS, their role in DVT treatment in the absence of a threatened limb is still unclear. The current ACCP guidelines recommend against their routine use in patients with DVT, except for those patients (without contraindication) with an extensive acute proximal DVT (ileofemoral DVT) or individuals at risk for limb gangrene secondary to venous occlusion.

Damage to the venous valves from lower extremity DVT and venous hypertension can lead to the development of PTS, a condition characterized by leg edema, skin changes such as hyperpigmentation and lipodermatosclerosis, pain, and, in severe cases, stasis ulceration. The incidence of this complication is drastically reduced with the use of compression stockings, and current guidelines recommend the use of stockings at a pressure of 30 to 40 mm Hg at the ankle for 2 years after an episode of DVT. In addition, early ambulation as tolerated after diagnosis is encouraged, as mobile patients with DVT do not require bed rest. b. Vena caval interruption. Current guidelines recommend against the routine insertion of IVC filters for the treatment of DVT. Indications for placement of IVC filters are as follows: a contraindication to anticoagulation,
a complication from anticoagulation, or recurrent thromboembolization despite adequate anticoagulant therapy. Relative indications for IVC filters are massive PE, iliocaval DVT, free floating proximal DVT, cardiac or pulmonary insufficiency, high risk of complications from anticoagulation (frequent falls and ataxia), or poor compliance. Retrievable filters can be considered for situations in which anticoagulation is temporarily contraindicated or there is a short duration of PE risk. IVC filter alone is not an effective therapy for DVT, and resumption of anticoagulation as soon as risk of bleed is acceptable is recommended.

c. Duration of treatment. The duration of treatment following the diagnosis of DVT is dependent on the risk of recurrence. Risk factors for recurrence include an idiopathic DVT, underlying hypercoagulable states (listed in subsequent text), and malignancy. In addition, placement of a permanent IVC filter, elevated d-dimer levels, advanced age, male sex, and increased BMI also place individuals at a higher risk for recurrence. The risk of recurrence is low while patients are on anticoagulation; however, clinicians must weigh the risk of bleeding against the risk of new thrombosis.

Current guidelines recommend 3 months of anticoagulation with a VKA targeting an INR of 2 to 3 for patients with a first episode of DVT secondary to a transient cause. Anticoagulation with a VKA for at least 6 to 12 months with a target INR of 2 to 3 is recommended for patients with a first episode of idiopathic DVT, although consideration should also be given for indefinite anticoagulation in this situation. Patients with the antiphospholipid syndrome, homozygous for FVL, or doubly heterozygous for FVL and prothrombin gene mutation should be considered for indefinite anticoagulation. Long-term (indefinite) anticoagulation is also recommended in patients with malignancy for as long as the cancer remains active, and in patients who have unexplained recurrent DVTs.