Bound to bleed: How altered albumin binding may dictate warfarin treatment outcome

Although non-vitamin-K anticoagulants are now the preferred option for stroke prevention in atrial fibrillation (AF), warfarin is still used in a significant number of patients. Warfarin dosing requirements are susceptible to drug interactions and genetic polymorphisms in metabolising enzymes. Human serum albumin (HSA) is a candidate modifier of warfarin pharmacokinetics, with hypoalbuminemia now shown to correlate with supratherapeutic INR levels and annual bleeding risk. Warfarin is highly bound to HSA, and a relatively small shift, resulting from displacement by other xenobiotics, hypoalbuminemia or reduced binding capacity, can potentially lead to marked alterations in the free warfarin fraction. Precisely how this relates to the actual concentration of free, pharmacodynamically active, warfarin, is not clear, since measurement of this critical moiety remains an unsolved caveat. Yet awareness how disease, nutrition and polypharmacy affect warfarin binding to HAS and how this may impact (or not) on bioavailability and outcome, is essential for optimal treatment.