Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis

In reply: We thank Blacker for his constructive and helpful comments. Our recommendations on bridging therapy in patients with atrial fibrillation were for patients with chronic atrial fibrillation who had not previously had a thromboembolic event.1 We do agree with Blacker that extreme care needs to be exercised in patients with atrial fibrillation and a previous thromboembolism. These patients should be managed along the same lines as patients who are at relatively high risk of recurrent thromboembolism. We also wish to emphasise that it is extremely important to assess each individual patient carefully, and to use the consensus guidelines as guiding principles, and not apply them blindly.

Dear and his colleagues correctly point out that there are several published studies that have confirmed increased warfarin sensitivity in allelic variants of the cytochrome P450 2C9 (CYP2C9) enzyme. Polymorphisms associated with reduced enzymatic activity have been reported to be associated with increased warfarin sensitivity. They suggest that determining the genotype of individuals before commencing warfarin therapy may be of benefit in reducing the incidence of over-anticoagulation in a select group of patients. We do not believe that this approach is currently practical or possible. From a practical point of view we recognise several reasons why patients become over-anticoagulated when treated with warfarin. In our article we discussed several important modifiers that contribute to an individual’s sensitivity to warfarin. While we agree that polymorphisms of the CYP2C9 gene on its own have been linked with increased sensitivity to warfarin, we are not aware of any studies showing a synergistic interaction of the polymorphism with other clinically recognised causes of increased warfarin sensitivity. Furthermore, we are not aware of any properly conducted studies that have attempted to address the clinical or economic viability of screening for CYP2C9 polymorphisms in patients for whom warfarin therapy is planned. Finally, the time required to obtain the results of this investigation would preclude its application in the routine management of patients who require warfarin therapy.

The letter by Lubicz highlights the difficulties encountered in bridging anticoagulant therapy in patients with prosthetic valves. As pointed out in our article, the management of these patients is controversial and mostly anecdotal.1 We believe that the recommendations in our article are useful for most patients, but would like to emphasise the need to consult with the relevant experts in order to avoid bleeding or thrombosis. We would not recommend routine full therapeutic anticoagulation therapy with heparin immediately after surgery, or the combined use of warfarin at any international normalised ratio (INR) with subcutaneous heparin before surgery. Such approaches are more likely to cause confusion and predispose the patients to either bleeding or the risk of thrombosis. Patients with prosthetic valves require careful handling, and involving experts in their management is critical.

Kamien’s comments are important and illustrate the difficulties in changing entrenched practices. We hope that our recommendations will go some way to improving the way we manage patients on warfarin therapy who are about to undergo surgery.