Superwarfarin intoxication of unknown etiology accompanying hemoperitoneum in a patient on fluconazole therapy.

We report a case of brodifacoum (superwarfarin) intoxication of unknown etiology presenting as hemoperitoneum after fluconazole administration for one week before the onset of symptoms. The initial prothrombin time (PT) and partial thromboplastin time (PTT) were markedly prolonged, although a mixing study with normal plasma showed that the corrected PT and PTT were in the normal range. Vitamin K-dependent coagulation factors (Factors II (5%), VII (8%), IX (4%), and X (6%)), and Protein C (16%) and Protein S (19%) activities were reduced. Although the patient denied ingesting rodenticides or medications other than an antifungal drug, fluconazole, superwarfarin toxicity was suspected; subsequently, his serum brodifacoum level was found to be positive. After administration of fresh frozen plasma (FFP) and oral vitamin K(1) for five days and following drainage of the hemoperitoneum, the patient's bleeding tendency stopped, with slow decreases in PT and PTT. Compared to previous reports of superwarfarin intoxication of unknown exposure, this case is distinct in that the severe bleeding tendency needed surgical management and involved a suspected drug interaction with fluconazole. Therefore, superwarfarin intoxication should be suspected in subjects with markedly prolonged PT and PTT of unknown etiology, since a drug interaction could amplify the toxicity from a small exposure to superwarfarin.