Prolonged coagulopathy related to coumarin rodenticide in a young patient : superwarfarin poisoning : case report - online article

Abstract

Superwarfarins (brodifacoum, difenacoum, bromodialone and chlorphacinone) are anticoagulant rodenticides that were developed in 1970s to overcome resistance to warfarin in rats. A 26-year-old previously healthy man was admitted to the emergency department with epigastric pain, severe upper and lower gastrointestinal haemorrhage, gingival bleeding and melena. The patient stated that he had been healthy with no prior hospital admissions and no personal or family history of bleeding diathesis. The patient, who later admitted attempted suicide, stated that he had taken 400 g rodenticide including brodifacoum orally for five days prior to admission to hospital. He had oral mucosal bleeding, numerous bruises over the arms, legs and abdomen, and an abdominal tenderness, together with melena. Laboratory tests revealed a haemoglobin level of 12.3 g/dl, leucocyte count of 9.1 × 10(9) /l, haematocrit of 28% and platelet count of 280 × 10(9) /l. The prothrombin time (PT) was > 200 s (normal range 10.5-15.2 s) and the activated partial thromboplastin time (aPTT) was 91 s (normal range 20-45 s). The INR (International normalised ratio) was reported to be > 17 (normal range 0.8-1.2). The thrombin time and plasma fibrinogen levels were in the normal range. The results showed the presence of brodifacoum at a concentration of 61 ng/ml, detected by reversed-phase liquid chromatography.

Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management

“…In addition, warfarin had the supreme advantage of having an antidote. If any nontarget exposures occurred, the effects could be reversed by vitamin K [2,12]. Through the 1950s to 1960s, additional rodenticide agents were developed with increased potency and length of action compared with warfarin.…”

“…With more severe degrees of VKOR inhibition, γ-carboxylation may become completely dependent on exogenous vitamin K [2,21,22].…”

“…Of note, 10 (71%) of the 14 deaths from case report data were associated with intracranial hemorrhage, and of the 10 reported cases of intracranial hemorrhage, only 1 (10%) survived. Within this closer review of LAAR exposures, brodifacoum was the most common offending agent-brodifacoum, 83/174 (48%); chlorophacinone, 24/174 (14%); LAAR not otherwise 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 specified, 67/174 (38%) [2][3][4][5][6][7][8]13,17,20,27,32,33,[38][39][40][41]43,[49][50][51]53,.…”

“…Most clinicians are familiar with the treatment of supratherapeutic INRs during warfarin anticoagulation. In contrast to warfarin, LAARs possess significantly longer durations of activity (see Table 5); therefore, prolonged and repeated vitamin K treatment is typically needed [2,13,22,61].…”

“…Never intended for human use, cases of human poisoning can be dramatic and yet difficult to recognize. Longacting anticoagulant rodenticide poisoning is a global health issue with cases reported in Turkey, Croatia, Taiwan, China, Australia, Argentina, and the United States [2][3][4][5][6][7][8]. This review will provide the reader with a comprehensive understanding of LAAR poisoning by presenting the historical development of vitamin K antagonists, epidemiology, pharmacology, and clinical aspects of LAAR poisoning and its diagnosis and clinical management.…”