Surgeon General's Workshop on Deep Vein Thrombosis

Panel 4: Treatment

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SLIDE 1: Panel 4: Treatment

Kenneth A Bauer, MD

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SLIDE 2: Timeline of Anticoagulation Options

1916

• Heparin

1950s

• Warfarin

1970s

1990s

• LMWH

2002

• Selective factor Xa inhibitor
• Direct thrombin inhibitors

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SLIDE 3: Current Anticoagulants

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SLIDE 4: Current antithrombotic agents: multi-targeted

Graphic of multi-targeted antithrombotic agents

Current therapies have multiple actions on the coagulation cascade

Limitations linked to difficulties in controlling efficacy/safety balance

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SLIDE 5: Advantages of LMWH over UFH

Better bioavailability and predictable pharmacokinetics

• VTE treatment using weight-based dosing with no need for laboratory monitoring

Longer half-life

• twice or once daily subcutaneous dosing

Lower rate of heparin-induced thrombocytopenia

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SLIDE 6: Selective Indirect Factor Xa inhibition

Graphic of Selective Indirect Factor Xa inhibition

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SLIDE 7: Fondaparinux

• Synthetic pentasaccharide
• Longer half-life than LMWH
• No laboratory monitoring required
• No reactivity with HIT antibodies
• Approved for prophylaxis of VTE following major orthopedic and abdominal surgery and for treatment of VTE

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SLIDE 8: Limitations of Warfarin

(Vitamin K Antagonists)

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SLIDE 9: Direct Factor Xa Inhibition

Graphic of Direct Factor Xa Inhibition

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SLIDE 10: Direct Thrombin Inhibition

Graphic of Direct Thrombin Inhibition.

First click: To appear "intrinsic and extrinsic activation and the arrows including factor IX and VII leading to factor X"

Second click: Arrow from factor X to factor Xa and all downward reactions leding to fibrin. Please delete "32 U"

Third click: The three arrows on the right side (TFPI and antithrombin). Please delete "1 ug" and "1000 ug".

Fourth click: The orange text on the left side and simultaneously orange circles around II, VII, IX and X

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SLIDE 11: Anticoagulant Treatment of Venous Thromboembolism

1. Initial treatment with adequate doses of heparin is important.
2. Warfarin can be initiated early.
3. Antithrombotic effect of warfarin requires reduction of prothrombin levels: this effect requires at least 4 days of treatment and the need for overlap with heparin.
4. DVT can be treated at home with LMWH/fondaparinux.
5. Unprovoked ("idiopathic") VTE is a chronic disease.
6. What is the optimal duration of initial treatment? Which patients require long term anticoagulant therapy and what should the INR intensity be?

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SLIDE 12: Recurrent Venous Thrombosis is Common Following a First Episode of Symptomatic DVT

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SLIDE 13: Duration of Anticoagulant Therapy

• First event with reversible or time limited risk factor
  • 3-6 months at INR 2-3
• Unprovoked VTE, first or second event
  • 6-12 months at INR 2-3, then consider
  • indefinite anticoagulation at INR 2-3 weighing recurrence versus bleeding risk (? INR 1.5-2)

• Special Situations - indefinite anticoagulation
  • First event with
    • Cancer until resolved (consider chronic LMWH)
    • Antiphospholipid antibody syndrome
    • Antithrombin deficiency or multiple genetic defects,
    • ? deficiencies of protein C or protein S

The American College of Chest Physicians (ACCP) published guidelines on the topic of duration of therapy in 2001. They suggested that patients be treated for 3 to 6 months for the first event if they have had a reversible or time-limited risk factor. Anticoagulation therapy should be continued for more than 6 months in patients presenting with first episode of idiopathic VTE. The 12-month to lifetime group is the most critical. This group includes the patient who develops DVT and has cancer that is unresolved or anticardiolipin antibody or antithrombin III deficiency. In addition, patients who develop a recurrent event, idiopathic or with thrombophilia, require 12 months to lifetime management.

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