What are the symptoms and treatment options for Deep Vein Thrombosis (DVT)?

From the Guidelines

Deep vein thrombosis (DVT) should be treated with anticoagulation therapy using direct oral anticoagulants (DOACs) such as apixaban, dabigatran, edoxaban, or rivaroxaban over vitamin K antagonist (VKA) for the first 3 months. This recommendation is based on the most recent and highest quality study, which suggests that DOACs have a similar magnitude of benefit to VKA but with a reduced risk of harm 1. The treatment duration is usually 3-6 months for provoked DVT and may be longer or indefinite for unprovoked cases.

Some key points to consider in the management of DVT include:

• Anticoagulation therapy should be initiated promptly to prevent serious complications like pulmonary embolism
• Compression stockings (20-30 mmHg) can help reduce swelling and post-thrombotic syndrome
• Patients should be encouraged to walk and stay active as tolerated, contrary to older advice about bed rest
• Elevation of the affected limb when sitting or lying down can also help reduce swelling

The condition occurs when blood flow is slowed (stasis), the vein wall is damaged, or the blood becomes more prone to clotting (hypercoagulability) - factors collectively known as Virchow's triad. Other studies have also suggested the use of anticoagulation therapy for DVT, including the use of low molecular weight heparin (LMWH) or fondaparinux over IV unfractionated heparin 1. However, the most recent and highest quality study recommends the use of DOACs over VKA for the first 3 months of treatment 1.

In terms of specific treatment regimens, the following options can be considered:

• Apixaban (10mg twice daily for 7 days, then 5mg twice daily)
• Dabigatran (150mg twice daily)
• Edoxaban (60mg daily after initial heparin)
• Rivaroxaban (15mg twice daily for 21 days, then 20mg daily)

It's worth noting that thrombolytic therapy may be considered for patients with limb-threatening DVT or for selected younger patients at low risk for bleeding with symptomatic DVT involving the iliac and common femoral veins 1. However, this should be done on a case-by-case basis and with careful consideration of the potential risks and benefits.

From the FDA Drug Label

In a double-blind design, patients without clinical signs and symptoms of VTE disease were randomized to a post-discharge regimen of either Enoxaparin Sodium Injection 40 mg (n = 131) once a day subcutaneously or to placebo (n = 131) for 3 weeks. A total of 262 patients were randomized in the study double-blind phase and all patients were treated. Patients ranged in age from 44 to 87 years (mean age 68. 5 years) with 43.1% men and 56.9% women. Similar to the first study the incidence of DVT during extended prophylaxis was significantly lower for Enoxaparin Sodium Injection compared to placebo, with a statistically significant difference in both total DVT (Enoxaparin Sodium Injection 21 [16%] versus placebo 45 [34%]; p = 0. 001) and proximal DVT (Enoxaparin Sodium Injection 8 [6%] versus placebo 28 [21%]; p = <0.001).

1. 3 Prophylaxis of Deep Vein Thrombosis in Medical Patients with Severely Restricted Mobility during Acute Illness In a double blind multicenter, parallel group study, Enoxaparin Sodium Injection 20 mg or 40 mg once a day subcutaneously was compared to placebo in the prophylaxis of deep vein thrombosis (DVT) in medical patients with severely restricted mobility during acute illness (defined as walking distance of <10 meters for ≤3 days)

Table 20 Efficacy of Enoxaparin Sodium Injection in Prophylaxis of Deep Vein Thrombosis in Medical Patients with Severely Restricted Mobility During Acute Illness

• Treatment failures during therapy, between Days 1 and 14. † VTE = Venous thromboembolic events which included DVT, PE, and death considered to be thromboembolic in origin ‡ CI = Confidence Interval Dosing Regimen Indication Enoxaparin Sodium Injection 20 mg daily subcutaneously n (%)Enoxaparin Sodium Injection 40 mg daily subcutaneously n (%) Placebo n (%) All Treated Medical Patients During Acute Illness 351 (100) 360 (100) 362 (100) Treatment Failure* Total VTE† (%) 43 (12.3) 16 (4.4) 43 (11.9) Total DVT (%) 43 (12.3)(95% CI‡ 8.8 to 15.7) 16 (4.4)(95% CI 2.3 to 6. 6)41 (11.3)(95% CI 8.1 to 14.6) Proximal DVT (%) 13 (3.7) 5 (1.4)14 (3.9)

1. 4 Treatment of Deep Vein Thrombosis with or without Pulmonary Embolism In a multicenter, parallel group study, 900 patients with acute lower extremity deep vein thrombosis (DVT) with or without pulmonary embolism (PE) were randomized to an inpatient (hospital) treatment of either (i) Enoxaparin Sodium Injection 1. 5 mg/kg once a day subcutaneously, (ii) Enoxaparin Sodium Injection 1 mg/kg every 12 hours subcutaneously, or (iii) heparin intravenous bolus (5000 IU) followed by a continuous infusion (administered to achieve an aPTT of 55 to 85 seconds).

Table 21 Efficacy of Enoxaparin Sodium Injection in Treatment of Deep Vein Thrombosis with or without Pulmonary Embolism IndicationDosing Regimen* Enoxaparin Sodium Injection 1. 5 mg/kg dailysubcutaneouslyn (%)Enoxaparin Sodium Injection 1 mg/kg q12hsubcutaneouslyn (%)Heparin aPTT AdjustedIntravenous Therapyn (%)

• All patients were also treated with warfarin sodium commencing within 72 hours of Enoxaparin Sodium Injection or standard heparin therapy † VTE = venous thromboembolic event (DVT and/or PE) ‡ The 95% Confidence Intervals for the treatment differences for total VTE were: Enoxaparin Sodium Injection once a day versus heparin (-3.0 to 3.5) Enoxaparin Sodium Injection every 12 hours versus heparin (-4.2 to 1.7) All Treated DVT Patients with or without PE298 (100)312 (100)290 (100) Patient OutcomeTotal VTE† (%)13 (4.4)‡9 (2.9)‡12 (4. 1) DVT Only (%)11 (3.7)7 (2.2)8 (2.8) Proximal DVT (%)9 (3.0)6 (1.9)7 (2.4) PE (%)2 (0.7)2 (0.6)4 (1. 4)

DVT Treatment and Prevention:

• Enoxaparin Sodium Injection significantly reduced the incidence of DVT compared to placebo in medical patients with severely restricted mobility during acute illness.
• Enoxaparin Sodium Injection was equivalent to standard heparin therapy in reducing the risk of recurrent venous thromboembolism (DVT and/or PE) in patients with acute lower extremity deep vein thrombosis (DVT) with or without pulmonary embolism (PE).
• Dabigatran etexilate capsules were demonstrated to be non-inferior to warfarin in the treatment and reduction in the risk of recurrence of deep venous thrombosis and pulmonary embolism in adult patients. Key points:
• Enoxaparin Sodium Injection is effective in preventing DVT in medical patients with severely restricted mobility during acute illness.
• Enoxaparin Sodium Injection is equivalent to standard heparin therapy in treating DVT with or without PE.
• Dabigatran etexilate capsules are non-inferior to warfarin in treating and reducing the risk of recurrence of DVT and PE. 2

From the Research

Diagnosis and Treatment of DVT

• Diagnosis of deep vein thrombosis (DVT) requires a multifaceted approach that includes clinical assessment, evaluation of pre-test probability, and objective diagnostic testing 3
• Common symptoms and signs of DVT are pain, swelling, erythema and dilated veins in the affected limb 3
• Anticoagulation is indicated to control symptoms, prevent progression and reduce the risk of post-thrombotic syndrome and pulmonary embolism 3

Anticoagulation Therapy

• Intravenous (IV) infusion of unfractionated heparin (UFH) followed by oral administration of warfarin remains the cornerstone of clinical treatment of DVT 4
• Subcutaneously administered low-molecular-weight heparin (LMWH) is at least as effective and as safe as IV UFH 4
• Direct oral anticoagulants (DOACs) are the preferred treatment for DVT because they are at least as effective, safer and more convenient than warfarin 3
• DOACs may require dose reduction or avoidance in patients with renal dysfunction, and should be avoided in pregnancy 3

Duration of Anticoagulant Therapy

• The optimal duration of anticoagulant therapy after DVT is still debated, as it depends on an individual patient's potential risk for recurrence or treatment-associated complications 4
• Patients are usually risk stratified on the basis of multiple clinical characteristics, including the location of thromboemboli, the presence or absence of cancer, and the presence of certain thrombophilic conditions 4
• High-risk patients often receive inpatient treatment with UFH or LMWH and are candidates for long-term (> or = 6 months) oral anticoagulation, whereas short-term anticoagulation (3 to 6 months) is usually indicated for patients who are at lower risk of recurrence or therapeutic complications 4

Special Considerations

• Cancer patients should receive low molecular-weight heparin over warfarin in the long-term treatment of VTE, and should be considered for extended anticoagulation at least until resolution of underlying disease 5
• Enoxaparin may be as safe and effective as UFH for VTE prophylaxis in medically ill patients receiving hemodialysis 6
• The risk of recurrent venous thromboembolism can be estimated through a two-step algorithm, including the features of the patient, the initial event, and associated conditions, as well as D-dimer levels and residual thrombosis at time of anticoagulant treatment discontinuation 5