Deep vein thrombosis medical therapy

Editors-in-Chief: C. Michael Gibson, M.S., M.D. Associate Editor-In-Chief: Ujjwal Rastogi, MBBS [1]

Deep Vein Thrombosis Microchapters
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Overview

The primary purpose of treatment is to prevent the following:

• Further clot extension,
• Acute Pulmonary embolism,
• Recurrence of thrombosis,
• Prevention of late complications such as:
  • the post-thrombotic syndrome
  • chronic thromboembolic pulmonary hypertension.

Anticoagulation

Main article: Anticoagulation

Anticoagulation is the usual treatment for DVT. In general, patients are initiated on a brief course (less than a week) of low molecular weight heparin, before they are started on a chronic (3 to 6 month) course of warfarin (or related vitamin K inhibitors).

An abnormal D-dimer level at the end of treatment, signals the need for continued treatment, in patients with first unprovoked proximal deep-vein thrombosis.

Anticoagulant therapy is indicated for patients with symptomatic proximal lower extremity DVT, since PE is a fatal complication occurring in half of the untreated patients within few days to weeks.

Five options are available for the initial treatment of DVT:

1. Low-molecular-weight heparin (LMWH) administered subcutaneous (SC), without monitoring.
2. IV unfractionated heparin (UFH), with monitoring.
3. SC UFH, with monitoring
4. Weight-based SC UFH, without monitoring.
5. SC fondaparinux, without monitoring

After diagnosis, the current approach is to start both heparin and warfarin (VKA) , and to discontinue heparin after 5 days provided the international normalized ratio (INR) is ≥ 2.0 for at least 24 h.

Parenteral Anticoagulants

Heparin

• Heparin binds to antithrombin and inactivates thrombin, factors IIa, Xa, IXa, XIa and XIIa; binds to heparin cofactor II and inactivates factor IIa; and binds to factor IXa and inhibits factor X activation.
• Unfractionated heparin is mainly used in patients with known renal insufficiency or those who need close monitoring for bleeding, as activated partial thromboplastin time can be checked every 2 hours and doses adjusted.
• The apparent biologic half-life of heparin increases from approximately 30 min after an IV bolus of 25 units/kg, to 60 min with an IV bolus of 100 units/kg, to 150 min with a bolus of 400 units/kg.
• Efficacy of heparin in the initial treatment of DVT or PE is highly dependent on dosage.
• Initial dosing of IV heparin for VTE is either weight-based (80 units/kg bolus and 18 units/kg/h infusion) or administered as a bolus of 5,000 units followed by an infusion of at least 32,000 units/d, to achieve aPTT value of 1.5-2.5 of the normal value.
• If heparin is given subcutaneously for treatment of VTE, there are at least two options: (1) an initial IV bolus of 5,000 units followed by 250 units/kg twice daily; or (2) an initial subcutaneous dose of 333 units/kg followed by 250 units/kg twice daily thereafter.
• The dose for acute coronary syndrome is lower as compared to the treatment of DVT
• The main side effects are heparin-induce thrombocytopenia and osteoporosis.
• One major advantage of heparin is that the anticoagulant effects can be reversed with IV protamine sulfate.

Low molecular weight heparin

• LMWH is administered subcutaneously and is available in various forms like Bemiparin, Dalteparin, Danaparoid, Enoxaparin, Nadroparin, or Tinzaparin.
• The recommended doses for treatment of PE/DVT are:
  • Enoxaparin : 1 mg/Kg body weight (twice daily). Dose is 30 mg daily for VTE prophylaxis.
  • Tinzaparin : 175 U/Kg body weight (once daily).
• The doses in case of renal insufficiency are not clear, except Enoxaparin. It is recommended that the dose of Enoxaparin should be reduced to 50% of the usual dose in patients with a creatinine clearance of <30 mL/min.

Factor Xa Inhibitor

• Fondaparinux binds to antithrombin and inhibits factor Xa.
• A fixed dose of 2.5 mg daily is used for thromboprophylaxis. In patients with moderate renal insufficiency (creatinine clearance of 30-50 mL/min), dose should be reduced by 50%.
• Recommended dosages for treatment of DVT or PE are:
  • Patient weighing <50 Kg (110 lb): 5 mg (once daily).
  • Patient weighing 50 Kg (110 lb) to 110 Kg (220 lb): 7.5 mg (once daily).
  • Patient weighing >100 Kg (220 lb): 10 mg (once daily).

Direct thrombin inhibitors

• Direct thrombin inhibitors bind to thrombin and block its activity. These include Hirudin, bivalurudin, and argatroban.

Hirudin

• The recommended dose of IV lepirudin for heparin induced thrombocytopenia is 0.15 mg/kg/h with or without an initial bolus of 0.4 mg/kg.
• The anticoagulant effect of lepirudin in this setting is monitored by using the aPTT, and the dose is adjusted to achieve a target aPTT ratio of 1.5 to 2.5 times control.
• When given for thromboprophylaxis after elective hip replacement surgery, desirudin is given subcutaneously at a dose of 15 mg twice daily without monitoring.

Bivalirudin

• Recommended dose of Bivalirudin is a bolus of 0.75 mg/kg followed by an infusion of 1.75 mg/kg/h for the duration of the procedure.
• Dose reduction should be considered in patients with moderate to severe renal impairment.

Argatroban

• Argatroban is used for the treatment and prevention of heparin-induced thrombocytopenia associated thrombosis and for anticoagulation during percutaneous coronary interventions when heparin is contraindicated because of a recent history of heparin-induced thrombocytopenia.
• Argatroban is given as a continuous IV infusion with an initial dose of 1 to 2 m g/kg/min and the dose is adjusted to maintain the aPTT ratio in the 1.5 to 2.5 range.

Warfarin

Main article: Warfarin

• The recommended therapeutic INR during the treatment of DVT or PE with warfarin is 2.0-3.0.

Direct factor Xa inhibitor

Rivaroxaban (orally active direct factor Xa inhibitor) has been studied in phase III clinical trials for prevention of VTE in hospitalized medically ill patients (MAGELLAN), treatment and secondary prevention of VTE (EINSTEIN). More than 8,000 patients were enrolled in the rivaroxaban clinical development program overall. The study showed that taking rivaroxaban once daily for 35 days was associated with a reduction in the risk of venous thrombosis, compared with standard 10-day treatment with enoxaparin by subcutaneous injection, in acutely ill medical patients. However, bleeding rates were significantly increased with rivaroxaban.

Compression stockings

Elastic compression stockings should be routinely applied "beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis". The stockings in almost all trials were stronger than routine anti-embolism stockings and created either 20-30 mm Hg or 30-40 mm Hg. Most trials used knee-high stockings. A meta-analysis of randomized controlled trials by the Cochrane Collaboration showed reduced incidence of post-phlebitic syndrome. The number needed to treat is quite potent at 4 to 5 patients need to prevent one case of post-phlebitic syndrome.