Warfarin Hypersensitivity in a Patient with Mechanical Valve: A Real Challenge for the Management of Life-Long Anticoagulant Treatment

Bleeding is the most common adverse effect of vitamin K antagonist (VKA) therapy. We describe the case of a patient who reported severe spontaneous bleeding episodes after starting treatment with warfarin-based anticoagulants following a mechanical mitral valve implant, although the international normalized ratio was within the therapeutic range. Exhaustive coagulation testing detected very low plasma factor IX (FIX) activity (FIX:C= 5 IU/dL) that increased to normal values(89 IU/dL) upon warfarin withdrawal. F9 gene sequencing revealed the presence of the p.Ala37Thr missense variation in the pro-peptide coding region. This substitution was previously associated with FIX hypersensitivity to warfarin. Patients with this variation are usually switched from VKA to direct oral anticoagulants or heparin. However, the current guidelines recommend warfarin for all patients with mechanical valves. Therefore, we determined the target plasma FIX levels in this patient to monitor warfarin therapy and allow effective anticoagulation without bleeding complications.