bromfenacoum and Drug-Overdose

The increased prevalence of rodents resistant to warfarin led to the development of the hydroxycoumarin anticoagulant brodifacoum. A 25-year-old man attempted suicide by consuming four boxes of d-CON Mouse-Prufe II; each box contains 42 g of bait that is 0.005% brodifacoum. He presented to a hospital nine days later with syncope, hematochezia, gross hematuria, epistaxis, anemia, and a severe coagulopathy. Radiographic studies were consistent with pleural, pericardial, and mediastinal hemorrhages. Vitamin K and fresh frozen plasma were given, and he was later discharged on oral phytonadione (vitamin K1). The patient's coagulopathy recurred, necessitating multiple plasma transfusions and prolonged treatment with oral phytonadione. Fifteen weeks after hospital discharge, he presented again with a history of additional brodifacoum ingestion. Neurologic status was initially normal, but in the emergency department he suddenly became comatose soon after emesis was induced with syrup of ipecac. Computed tomography of the brain revealed a subarachnoid hemorrhage that led to brain death less than 24 hours later. This case demonstrates the severe and prolonged coagulopathy that can result from ingestion of brodifacoum, a compound that has a toxic potency about 200-fold that of warfarin and a half-life as much as 60 times longer.

Topics: 4-Hydroxycoumarins; Adult; Blood Coagulation Disorders; Blood Transfusion; Drug Overdose; Emergency Service, Hospital; Humans; Ipecac; Male; Partial Thromboplastin Time; Patient Readmission; Phenobarbital; Plasma; Poisoning; Prothrombin Time; Rodenticides; Subarachnoid Hemorrhage; Suicide; Tomography, X-Ray Computed; Vitamin K

A case of brodifacoum overdose and its treatment with prothrombin complex concentrate (PCC) are reported.. A 44-year-old Caucasian woman weighing 62 kg arrived at the emergency department with a chief complaint of lower left leg pain for two days. A computed tomography (CT) scan of the abdomen revealed perihepatic fluid collection (likely a hematoma), a small-bowel intramural hematoma, and blood in the paracolic gutter. A CT scan of the patient's left foot showed soft tissue swelling without evidence of fracture or dislocation. The patient was diagnosed with left extremity compartment syndrome secondary to hematoma and trauma. The patient had a history of depression and anxiety and eventually admitted to ingesting large doses of brodifacoum the week prior with suicidal intentions. The patient was treated with phytonadione 20 mg i.v., 1 unit of fresh frozen plasma (FFP), and 1 unit of packed red blood cells. Laboratory test values measured in the intensive care unit revealed an International Normalized Ratio (INR) of 15, a prothrombin time of >120 seconds, and a partial prothromboplastin time of >180 seconds. After consulting with a local poison center, phytonadione 50 mg i.v., PCC 3100 units, and 4 units of FFP were immediately administered to reverse the patient's coagulopathy. The dose of oral phytonadione was lowered based on INR stability. Once the coagulopathy was stabilized, the patient was transferred to an inpatient psychiatric facility on phytonadione 10 mg daily orally to maintain a stable INR.. A 44-year-old woman who intentionally ingested brodifacoum was successfully treated with phytonadione, PCC, and FFP.

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Blood Coagulation Factors; Drug Overdose; Female; Humans; Prothrombin Time; Treatment Outcome

The use of second-generation anticoagulants termed "superwarfarins" as rodenticides, although widespread, is poorly controlled. Products containing superwarfarin have been marketed in over-the-counter rodenticides and can be easily purchased. Poor control potentiates the risk of accidental or intentional poisoning, but clinicians may underestimate the incidence of superwarfarin toxicity. Therefore, when cases of unexplained acquired coagulopathy and selective deficiency of vitamin K-dependent clotting factors occur in patients in the absence of liver disease or inhibitors, physicians should consider the possibility of superwarfarin poisoning as a cause. According to our own experience, recombinant activated factor VII (NovoSeven; Novo Nordisk, Bagsvaerd, Denmark) appears to be a safe and effective therapy for acute bleeding caused by superwarfarin poisoning. Due to the extended half-life of the second-generation rodenticides, follow-up therapy with oral vitamin K1 should be of long-term duration.

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Blood Coagulation Tests; Diagnosis, Differential; Drug Overdose; Factor VII; Factor VIIa; Female; Hemorrhage; Humans; Male; Recombinant Proteins; Rodenticides

Ingestion of long-acting anticoagulant rodenticides such as brodifacoum can lead to prolonged and life-threatening coagulopathy. A paucity of conflicting information is available on brodifacoum's half-life and elimination pharmacokinetics. In addition, the optimal dose, duration, and route of administration of vitamin K(1) therapy are unknown. We report the case of a 52-year-old man who ingested eight 43-g boxes of a rodenticide (d-Con Mouse-Prufe II; 0.005% brodifacoum; Reckitt & Colman, Wayne, NJ). This case demonstrates that after stabilization with fresh frozen plasma, high-dose oral vitamin K(1) therapy ( congruent with 7 mg/kg per 24 hours divided every 6 hours) was effective in treating brodifacoum-induced coagulopathy. The concentration of vitamin K(1) required for normal coagulation in this case was less than the accepted value of 1 microg/mL, which is derived from a rabbit model. In this case, brodifacoum appears to follow zero-order elimination pharmacokinetics. In future cases of patients with ingestions of long-acting anticoagulants who present with coagulopathy, it may be useful to obtain serial brodifacoum concentrations to determine elimination curves to help predict the duration of oral vitamin K(1) therapy.

Topics: 4-Hydroxycoumarins; Administration, Oral; Drug Overdose; Follow-Up Studies; Half-Life; Hemorrhage; Humans; Male; Metabolic Clearance Rate; Middle Aged; Plasma; Rodenticides; Suicide, Attempted; Vitamin K

Brodifacoum is a 4-hydroxycoumarin derivative that is commonly used as a rodenticide. Human exposures have produced severe coagulopathies resulting in hematuria, gastrointestinal bleeding, intracranial hemorrhage, and death. This is the first report of spontaneous hemoperitoneum secondary to brodifacoum ingestion. The patient was successfully managed with fresh frozen plasma, packed red blood cells, and vitamin K1. No surgical intervention was performed. The patient required ongoing daily vitamin K1 therapy for longer than 6 months.

Topics: 4-Hydroxycoumarins; Adult; Blood Component Transfusion; Drug Overdose; Erythrocyte Transfusion; Female; Hemoperitoneum; Humans; Plasma; Poisoning; Rodenticides; Vitamin K

Topics: 4-Hydroxycoumarins; Adult; Drug Overdose; Factitious Disorders; Female; Humans; Prothrombin Time; Vitamin K 1