Tuesday, October 4, 2011

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Venous thrombo embolism / Pulmonary embolism - Anticoagulation

As soon as a diagnosis of VTE / PE is strongly suspected, anticoagulant therapy should be started unless there are contraindications. Parenteral drugs like unfractionated heparin (standard heparin) and low molecular weight heparin (lovenox) are started and therapy shifted to a long term stable vitamin K antagonist like warfarin.

Unfractionated heparin
The anticoagulant action is by binding to and accelerating the activity of antithrombin III. This inactivates thrombin, factor IXa and Xa and thus prevents further clot formation. The classical regimen for the dosage is a loading dose of 5000 - 10000 units followed by a continuous infusion of 1000 - 1500 units/hour. Unfortunately we all do not have the same weight. So, a more appropriate dosage is a loading dose of 80 units/kg and a continuous infusion of 18 units/kg/hr.

The aim is to achieve a target activated partial thromboplastin time (aPTT) aka partial thromboplastin time with kaolin (PTTK) of 2-3 times the normal laboratory values, the normal values being 30-40 seconds.

The PTTK is checked every 4-6 hours and the infusion is adjusted accordingly.

Low molecular weight heparin
Enoxaparin (lovenox) is given in a dosage of 1 mg/kg twice daily. The advantages over unfractionated heparin is that it binds less to plasma protein and endothelial cells. So the bioavailability is higher and the half life is longer. The dose response is more predictable. No repeated tests are required for monitoring but care must be taken to lower the dosage in patients with renal insufficiency.

Warfarin
This vitamin K antagonist prevents the gamma carboxylation activation of factors II,VII,IX and X, as well as the proteins C and S. The anticoagulant effects appear only after 5 days because factor II has a half life of 5 days.

The dosage to be used initially is between 5 - 10 mg/ day. We should aim for an INR between 2.0 - 3.0.

Warfarin is a difficult drug to dose and monitor as it has multiple drug-drug and drug-food interactions.

Warfarin should be started as soon as the PTTK is within the therapeutic range. The heparin should be continued until a therapeutic INR has overlapped with a therapeutic PTTK for 2 consecutive days. This usually occurs after a minimum of 5 days.

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