Acquired coagulopathy caused by intoxication with the superwarfarin-type anticoagulant rodenticide flocoumafen.
A 28 year-old heretofore healthy woman was transferred to our hospital with a two-month history of recurring episodes of bleeding. Administration of vitamin K and prothrombin complex concentrates in the transferring hospital had only temporarily corrected both the markedly elevated international normalized ratio (INR) and the prolonged activated partial thromboplastin time (aPTT). The patient's medical and family history revealed no reason for these abnormalities. Our laboratory analyses revealed a sustained deficiency of vitamin K-dependent clotting factors. Presence of an acquired inhibitor of clotting factors was excluded. Thus we suspected, intoxication with an anticoagulant rodenticide. Liquid chromatography-mass spectrometry (LC-MS/MS) revealed pharmacologically active concentrations of flocoumafen, a rodenticide belonging to the superwarfarin family, in the patient's serum. While the long elimination half-life of superwarfarins is well described in rodents, information on pharmacokinetics in humans is not yet available. Therefore, patient management was not limited to prolonged administration of vitamin K, but also included repeated measurements of flocoumafen serum levels. During follow-up visits, clotting tests remained normal and flocoumafen levels gradually decreased, reaching the limit of quantification after 48 days. Based on the repeated measurements of flocoumafen serum levels, a half-life of 6.7 days was estimated in our patient, which is in clear contrast to the 220 days reported in rodents. Thus, monitoring flocoumafen serum concentrations in affected patients may provide a rational basis for the duration of vitamin K substitution and adequate follow-up intervals.
Department of Hematology/Oncology, University of Tuebingen Medical School, Otfried-Mueller-Strasse 10, Tuebingen, Germany.
Steffen
S
Boettcher
Alexander
A
Wacker
Klaus
K
Moerike
Hans-Georg
HG
Kopp
Karl
K
Jaschonek
Thomas
T
Grobosch
Lothar
L
Kanz
Helmut R
HR
Salih
D015110:4-Hydroxycoumarins / Q000506:poisoning*; D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods; D004211:Disseminated Intravascular Coagulation / Q000175:diagnosis* / Q000209:etiology*; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D013058:Mass Spectrometry / Q000379:methods; D010314:Partial Thromboplastin Time; D012378:Rodenticides / Q000506:poisoning*; D014812:Vitamin K / Q000627:therapeutic use; D014859:Warfarin / Q000506:poisoning*
D015110:4-Hydroxycoumarins; D012378:Rodenticides; D014812:Vitamin K; C048069:flocoumafen; D014859:Warfarin