Covert poisoning with difenacoum: clinical and toxicological observations.
1. The coumarin anticoagulant difenacoum was detected by high performance liquid chromatography (HPLC) with multi-wavelength UV detection in plasma from a 41 years old man who presented with a severe deficiency of vitamin K-dependent clotting factors of unknown aetiology. A longitudinal toxicological study of the consequent coagulopathy is described. 2. Plasma concentrations of difenacoum declined from 0.97 to 0.11 mgl-1 in 47 days with a terminal half life of 11.7 days. Rifampacin (300 mg bd) had no apparent effect on the terminal half life of the drug. Subsequently plasma concentrations of difenacoum and descarboxyprothrombin (DCP) unexpectedly increased. 3. Seven months after exposure clotting times were prolonged. The patient continued to have episodes of epistaxis, haematoma, purpurae and bruising and he required frequent treatment with Fresh Frozen Plasma in additional to oral phylloquinone (200 mg day-1). 4. Intermittent and unexpected increases in plasma concentrations of difenacoum and descarboxypro-thrombin suggested that covert, repeated ingestion of the anticoagulant was the most likely cause of the poisoning. The measurement of low concentrations of plasma phylloquinone except following supervised ingestion of the vitamin indicated that as an outpatient, the subject was not compliant with treatment despite his protestations to the contrary. He continued to deny this even when confronted by laboratory findings and at no time did he ever admit to self-poisoning.
McCarthy
P T
PT
Haemophilia Centre, St. Thomas' Hospital, London, UK.
Cox
A D
AD
Harrington
D J
DJ
Evely
R S
RS
Hampton
E
E
al-Sabah
A I
AI
Massey
E
E
Jackson
H
H
Ferguson
T
T
D015110:4-Hydroxycoumarins / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000494:pharmacology; D000925:Anticoagulants / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers; D001779:Blood Coagulation Factors / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006207:Half-Life; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010949:Plasma; D011498:Protein Precursors; D011516:Prothrombin / Q000031:analogs & derivatives / Q000378:metabolism; D012293:Rifampin / Q000008:administration & dosage / Q000494:pharmacology; D012378:Rodenticides / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D013056:Spectrophotometry, Ultraviolet; D010837:Vitamin K 1 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D015110:4-Hydroxycoumarins; D000904:Antibiotics, Antitubercular; D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D015415:Biomarkers; D001779:Blood Coagulation Factors; D011498:Protein Precursors; D012378:Rodenticides; C008208:acarboxyprothrombin; D010837:Vitamin K 1; D011516:Prothrombin; C012903:difenacoum; D012293:Rifampin