<Internation Circulation>:What are the problems that are remaining unresolved with anticoagulation therapy in clinical practice?

Suzanne Hughes:It is well known that Wafarin is a very effective medication that has been around for a long time.  But unfortunately Warfarin is far from being a perfect drug.  One of the several drawbacks about Warfarin is that it has what we call a ‘narrow therapeutic index’ (NTI).  This means there is less than a two-fold difference in the median lethal dose and the median effective dose.  Put another way: there is less than a two-fold difference between the minimum toxic concentration and the minimum effective concentration of Warfarin in the blood.  So when you have an agent that has NTI it means that safe and effective use of this product requires very careful titration and patient monitoring.   When we have a patient on oral anticoagulation， for most indications， the target International Normalised Ratio (INR) range is somewhere between 2 and 3.  Anytime the INR range gets above three， we see an increase in the risk of hemorrhagic complications， the most devastating being intracranial bleeding.   But when we get below an INR of 2， we see an increased risk of thrombotic issues， namely ischemic stroke.  In fact， even at an INR level as close to 2 as 1.8， we see almost a doubling of the risk of thrombosis.  So it is very clear that with Warfarin a very narrow tightrope must be walked to keep the patient exactly where they should be to minimize bleeding risk but also to prevent thrombosis.