The major risk associated with the use of vitamin K antagonists (VKA) is haemorrhage, which might be severe or even life-threatening. In clinical studies where anticoagulation intensity was carefully monitored, treatment with VKA increases the risk of major bleeding by 0.3-0.5% per year when compared to controls [1]. In randomized trials including patients with mechanical heart valves, VKA treatment was associated with a risk of major bleeding ranging between 1 and 8.3% [1]. However, in clinical practice, the rates are less consistent [1]. The major determinants of VKA-induced bleeding are the intensity of the anticoagulant effect, the patient characteristics, the concomitant use of drugs that interfere with hemostasis, and the length of therapy [1]. Here, we report a case of a rare hypersensitivity to VKA due to a mutation of factor IX (FIX) propeptide in the context of a prosthetic mechanical heart valve. In November, 2008, a 62-year-old man presented with an obstructive laryngeal hematoma (Fig. la, b) after tongue biting requiring intratracheal intubation. His medical history revealed prosthetic mechanical aortic valve replacement in July 2008 (Bentall procedure, Cardiomedic prosthesis). Oral anticoagulation with VKA (acenocoumarol) was initiated post-operatively. When the laryngeal hematoma appeared, the patient's International Normalized Ratio (INR) was 3.5. In December, 2008, the patient was admitted to the intensive care unit with a massive hemothorax (Fig. 1c) occurring 10 days after a reintervention to cure a paraprosthetic leak, and requiring surgical drainage. INR was 1.3. The patient's and his relatives reported no history of bleeding. Aspirin, the only patient's medication favoring bleeding, had been stopped 4 days before the first bleeding episode. Before the introduction of acenocoumarol, blood count, prothrombin time (PT) and activated partial thromboplastin time (APTT) were within the normal range. Coagulation tests are listed in Fig. 1d. Both major bleeding episodes were accompanied by INR values within or even below the therapeutic range (therapeutic range for a mechanical valve carrier: 2.5-3.5) [2]. However, APTT was abnormally prolonged because FIX was exaggeratedly lower than the other vitamin K dependant factors (II, VII, X). Factor V, VIII, XI and XII were within the normal range during both bleeding episodes. APTT and FIX both normalized after vitamin K supplementation and bleeding did not recur. Genomic DNA was purified from the patient whole blood, and FIX exon 2 was amplified using the forward primer 5'-catgccctaaagagaaattggct-3' and the reverse primer 5'-tgcatctgaagggtattatgtgg-3'. The thermocycling conditions of the PCR were 30 s 94°C, 1 min 53°C, and 1 min 72°C, for 40 cycles. Direct sequencing of the PCR product showed a single guanosine-to-adenosine transition at nucleotide 109 (numbered from genBank accession gi180552) causing the substitution of alanine at locus-10 (Ala-10) by threonine in the FIX propeptide (Fig. 2a).