The Bile Sequestrant Cholestyramine Increases Survival in a Rabbit Model of Brodifacoum Poisoning.

Patients exposed to long acting anticoagulant rodenticides (LAARs) are typically administered large amounts of oral vitamin K1 (VK1) to counteract life-threatening anticoagulant effects. Although VK1 treatment effectively prevents mortality, additional methods are needed to reduce the long duration of VK1 treatment which can last for months at high expense. We developed a model of brodifacoum (BDF) poisoning, one of the most potent LAARs, in adult male New Zealand White (NZW) rabbits. The LD50 for oral BDF was determined to be 192 µg/kg, similar to that calculated for adult rats. However, in contrast to rats, NZW rabbits exhibited severe internal hemorrhage including in the brain, symptoms which mimic what occurs in cases of human poisoning. Similar to warfarin, BDF and other LAARs undergo enterohepatic recirculation which contributes to their long half-lives. We therefore tested effects of cholestyramine (CSA), an FDA-approved bile sequestrant, on BDF-induced mortality. When given daily (0.67 g/kg, oral) starting the day of BDF administration, CSA reduced mortality from 67% to 11%. At the same CSA prevented the increase in clotting time, and reduced the decrease in core body temperature due to BDF. Given its excellent safety record and that it is approved for children older than 6 years, these findings suggest CSA could be considered as an adjunct to VK1 for treatment of LAAR poisoning.

Superwarfarin poisoning in children: a prospective study.

This prospective study was undertaken to determine the incidence, severity, time of onset, and duration of coagulopathy in children following accidental ingestion of long-acting anticoagulant rodenticides, often called "superwarfarins." Of 110 children, who ingested superwarfarins and in whom one or more prothrombin time values were obtained, 8 had a prothrombin time ratio (patient to control) of greater than or equal to 1.2, indicative of anticoagulation. Prothrombin time values obtained 48 hours after ingestion were more likely to be prolonged (6/34, 17.6%) than values obtained 24 hours after ingestion (2/104, 1.9%) (P less than .005). The occurrence of an abnormal prothrombin time could not be predicted based on the history of amount ingested or on the presence of the characteristic green-blue product dye in or around the child's mouth. Acute toxicity was evidenced by transient abdominal pain, vomiting, and heme positive stools in 2 patients. The duration of prothrombin time prolongation could not be determined because of the few values obtained after 48 hours. To detect all possible abnormal prothrombin time values, 24- and 48-hour determinations are recommended after a child has ingested a superwarfarin.

Superwarfarin and glass ingestion with prolonged coagulopathy requiring high-dose vitamin K1 therapy.

A 23-year-old man was brought to the emergency department after eating four boxes of brodifacoum-containing rodenticide over a 4-day interval and pieces from approximately two bottles of glass over the previous 2 weeks. He was asymptomatic but his prothrombin time was markedly elevated with an international normalized ratio (INR) of 37.8. A plain abdominal film showed diffuse radiopaque foreign bodies, presumably glass, in the large and distal small intestines. Treatment for ingested glass consisted of stool softeners and bulk-forming laxatives. The patient developed mild gingival bleeding and received fresh frozen plasma (FFP) infusions and vitamin K1 orally. At a vitamin K1 dosage of 300 mg/day, the INR corrected to less than 2.0 and the patient was discharged taking that dosage. He returned 26 days later with hematuria and flank pain, and his INR was 189. He was administered FFP and packed red blood cells, and his vitamin K1 dosage was increased to 800 mg/day; his INR returned to baseline. Compliance with taking the vitamin K1, which required ingestion of 60-160 tablets/day, was a serious problem, requiring numerous follow-up calls and visits to the patient at home and work. At 5-month follow he was doing well. Compliance with large daily doses of vitamin K1 for treatment of "superwarfarin" ingestion may be poor because of the duration of treatment and large number of pills required. A more concentrated formulation may be advantageous for management of patients with brodifacoum poisoning.

Prolonged coagulopathy related to coumarin rodenticide in a young patient: superwarfarin poisoning.

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.

Spontaneous hemorrhage associated with accidental brodifacoum poisoning in a child.

A 36-month-old child had spontaneous hemorrhage from her nose, mouth, and urinary tract, and a fall in hemoglobin of 20 gm/L (2 gm/dl). The prothrombin time and partial thromboplastin time were markedly prolonged with a decrease in the vitamin K-dependent factors. The child had ingested brodifacoum, a long-acting rodenticide. Prolonged follow-up and treatment with vitamin K were necessary.