brodifacoum human ingestion

Patients from northern Wisconsin with superwarfarin exposure or poisoning were examined at a tertiary referral center in rural Wisconsin to determine what led to their exposure and to review the clinical manifestations, diagnosis, treatment, and prevention of superwarfarin poisoning. Litovitz  JNSadowski Pestoff brodifacoum cereal baits Risks to humans The poison poses a low risk when used correctly.  LRRobert That’s equivalent to … Management of brodifacoum poisoning is case dependent on the amount of exposure and INR status.  SMConstable Weitzel Stanton T, Sowray P, McWaters D, Mount M. Prolonged anticoagulation with long-acting coumadin derivative: Case report of a brodifacoum poisoning with pharmacokinetic data. Get the latest from JAMA Internal Medicine.  M Prolonged anticoagulation with long-acting coumadin derivatives: case report of a brodifacoum poisoning with pharmacokinetic data. There have been 11 cases of Munchausen syndrome,6-9,23-27 6 attempted suicides,19,20,28-31 2 industrial exposures,21 3 cases of unknown cause,18,32 1 case of accidental ingestion,15 and 1 case involving a psychiatric disorder.22 Poisoning in the adults and the teenager in our study resulted from 2 suicide attempts and 2 cases of Munchausen syndrome.  BFHolm None of the children had documented elevated PTs, clinical signs of coagulopathy, or complications. A deficiency of vitamin K–related factors plus a very high vitamin K1 epoxide–reduced vitamin K1 ratio is consistent with warfarin or superwarfarin poisoning.36,37 Vitamin K1 epoxide is a product of vitamin K metabolism and is the inactive form of vitamin K (Figure 1). The widespread use of these molecules raises questions on exposure and intoxication risks, which define the safety of these products.  BRPastoor One child received 5 mg of vitamin K subcutaneously, and 5 children received syrup of ipecac.  BKChoonara Exposure was defined as any history of oral intake or inhalation of superwarfarin, or superficial contact with a superwarfarin near the oral mucosa without any biochemical or clinical manifestations of coagulopathy. Although he had been instructed to take oral vitamin K1, it was discovered that he never had the prescription filled. For permissions, please e-mail:, Daratumumab Interference in Flow Cytometry Producing a False Kappa Light Chain Restriction in Plasma Cells, Incidence of Hepatotoxicity in Iranian Patients With HIV on Antiretroviral Therapies and Its Correlation with Virologic Response to HIV Treatment, Machine Learning Prediction of SARS-CoV-2 Polymerase Chain Reaction Results with Routine Blood Tests, Strategies for Sustainability of University-Based Medical Laboratory Sciences Programs, Absolute Lymphocytes, Ferritin, C-Reactive Protein, and Lactate Dehydrogenase Predict Early Invasive Ventilation in Patients With COVID-19, high pressure liquid chromatography procedure, About the American Society for Clinical Pathology,, Receive exclusive offers and updates from Oxford Academic, Trace Elements: When Essential Nutrients Become Poisonous: Separating Fact From Fiction, Rat Poisoning: A Challenging Diagnosis With Clinical and Psychological Implications, Plasma Transfusion Demystified: A Review of the Key Factors Influencing the Response to Plasma Transfusion, The Cost of Pre-Analytical Errors in INR Testing at a Tertiary-Care Hospital Laboratory: Potential for Significant Cost Savings.  TLFelberg  DJC Quantification of brodifacoum in plasma and liver tissue by HPLC. Here, we present the case of a patient with toxicity related to use of brodifacoum-laced synthetic marijuana. Diagnosis of brodifacoum poisoning can be challenging, especially if the patient is not forthcoming about having ingested rat poison or is unable to provide a history of ingesting the substance. Clinical manifestations are challenging to diagnose if the patient cannot provide information regarding exposure. The results of his initial screening for superwarfarins were negative.  GHNaiman  SKlein-Schwartz Litovitz  JB A comparison of vitamin K antagonism by warfarin, difenacoum and brodifacoum in the rabbit. Although psychiatric evaluation may be indicated, patients with Munchausen syndrome rarely comply with therapy. Hadler She was sent home and found to be normal on follow-up 3 days later with no clinical signs of coagulopathy.  FHumphrey excessive bruising, nose and gum bleeding, and blood in the urine and. Get free access to newly published articles. After transient resolution, repeated and continuous treatment with large doses of vitamin K1 was necessary to correct the coagulopathy. According to the Centers for Disease Control and Prevention (), pesticide poisoning was the 10th biggest cause of poisoning in the US in 2011.It was responsible for roughly 40,000 emergencies that year.  A Anaphylactic shock and vitamin K. From the Marshfield Clinic, Marshfield, Wis. Dr Chua is now with the Cleveland Clinic Foundation, Cleveland, Ohio.  JM Death following ingestion of superwarfarin rodenticide: a case report.  RSSmilkstein Cases may be associated with accidental exposure, suicide attempts, or Munchausen syndrome, and may be difficult to diagnose. Corresponding author: William R. Friedenberg, MD, Department of Hematology/Oncology, Guthrie Clinic, Guthrie Square, Sayre, PA 18840.  LWhite The vitamin K1 epoxide–reduced vitamin K ratio confirmed the presence of a warfarin-type compound while assays for warfarin were being performed. Our website uses cookies to enhance your experience. The incidence of brodifacoum (superwarfarin) exposures and poisoning from 1988 to 1994.11-17. Ingestion and other exposures to the chemical can cause various symptoms.  BHedHess The INR of the patient was monitored every 6 hours; the patient subsequently received 30 units of plasma during a 4-day period (, Accidental poisoning with a superwarfarin compound (brodifacoum) in a child, Brodifacoum intoxication with marijuana smoking, Korean patients with superwarfarin intoxication and their outcome, Novel 4-hydroxycoumarin anticoagulants active against resistant rats, 2013 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 31st Annual Report, How I treat poisoning with vitamin K antagonists, Long-acting anticoagulant overdose: brodifacoum kinetics and optimal vitamin K dosing, Vitamin K treatment of brodifacoum poisoning in a pregnant woman, Evaluation of risk factors in patients with vitamin K-dependent coagulopathy presumed to be caused by exposure to brodifacoum, Pharmacologic agents in the management of bleeding disorders, Surreptitious ingestion of a long-acting vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of three cases, Prolonged coagulopathy after brodifacoum exposure, Cutaneous exposure to warfarin-like anticoagulant causing an intracerebral hemorrhage: a case report, Intracerebellar hemorrhage caused by superwarfarin poisoning, Superwarfarin poisoning: a report of two cases and review of the literature, National Center for Health Statistics; 2014, Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, Bench-to-bedside review: optimising emergency reversal of vitamin K antagonists in severe haemorrhage–from theory to practice, Beriplex P/N Anticoagulation Reversal Study Group, Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial, Successful emergency reversal of phenprocoumon anticoagulation with prothrombin complex concentrate: a prospective clinical study, Efficacy and safety of a prothrombin complex concentrate (Octaplex) for rapid reversal of oral anticoagulation, Rapid reversal of oral anticoagulation with warfarin by a prothrombin complex concentrate (Beriplex): efficacy and safety in 42 patients, Optimal dose of prothrombin complex concentrate for acute reversal of oral anticoagulation, Beriplex P/N reverses severe warfarin-induced overanticoagulation immediately and completely in patients presenting with major bleeding, Identification of prothrombin as a major thrombogenic agent in prothrombin complex concentrates, Pharmacokinetics of Beriplex P/N prothrombin complex concentrate in healthy volunteers, © American Society for Clinical Pathology, 2015. Normalization of the PT and APTT after mixing studies implies the presence of factor deficiency and the absence of an inhibitor. Nausea and vomiting may occur soon after ingestion. Underwood EL, Sutton J, Ellis IK, Qualls B, Zamber J, Walker BN. If Brodifacoum was ingested by your dog, it is best to see your vet for help. The acute oral toxicity of the anticoagulant brodifacoum to dogs M. E. R. GODFREY, T. C. REID, ANDH. Treatment for superwarfarin poisoning requires long-term outpatient care.  D Symptomatic brodifacoum ingestion requiring high-dose phytonadione therapy. In our first case, levels of all the vitamin K–dependent factors were low and the factor V level was normal, which is consistent with a lack of vitamin K1 or inhibition of its activity by warfarin or superwarfarin. The chemical may be absorbed through the skin. We reviewed the records of 11 patients found to have superwarfarin poisoning over 15 years. Multiple admissions and evaluations6-9 are reported for this disorder when it is a manifestation of Munchausen syndrome. Weitzel JN, Sadowski JA, Furie BC, et al. 1. The dose of phenobarbital is 100 to 180 mg/d.5. Eleven cases (7 children, 1 teenager, and 3 adults) satisfied the criteria of superwarfarin exposure or poisoning. Cases may be associated with accidental exposure, suicide attempts, or Munchausen syndrome, and may be difficult to diagnose. At admission to the hospital, the patient reported chest pain and admitted to having inhaled rat poison a few hours previously.  PKim  KMSchmitz Mowry JB, Spyker DA, Cantilena LRJr, McMillan N, Ford M. Bruno GR, Howland MA, McKeeking A, Hoffman RS.  TLClark CLINICAL EFFECTS 9.1 Acute poisoning 9.1.1 Ingestion Ingestion of brodifacoum is initially asymptomatic, and may continue as such even with prolonged alterations in prothrombin time. None of the patients in our study died of superwarfarin poisoning.  IZuazu Brodifacoum is a common household rodenticide that has been implicated in suicide, homicide, accidental ingestion, and even in the lacing of recreational drugs.1-4 Brodifacoum is 100 times as potent as warfarin5 and in 2013, there were 8783 cases of superwarfarin poisoning reported.6 Patients who ingest brodifacoum develop severe deficiencies in the vitamin K–dependent coagulation factors (II, VII, IX, and X), typically resulting in elevated prothrombin time (PT) and activated partial thromboplastin tim… It is very popular and poses a greater secondary risk like Difethialone to predators and scavengers.  JGrau Vitamin K1 Treatment Duration in Brodifacoum Poisoning The rodenticide brodifacoum, a long-acting vitamin K epoxide cycle antagonist, can produce life-threatening hemorrhage in exposed humans. In recent years, it has become one of the world's most widely used pesticides. Furthermore, we advise physicians to obtain samples of a few of the vitamin K–dependent factors (II, VII, IX, and X) and factor V, which is produced in the liver but is not vitamin K dependent.  DL An acquired hemorrhagic disorder from long-acting rodenticide ingestion.  RAKlass Ten-day laboratory assessment for our patient, a 21-year-old Caucasian man, after brodifacoum inhalation. We also suggest that for patients with possible Munchausen syndrome, a mixing study of the patient's plasma with control plasma should be performed. Brodifacoum inhalation is a relatively new route of exposure, and little is known about its pharmacokinetic effects. Laboratory studies yielded the following values: PT, greater than 90 seconds; APTT, greater than 160 seconds; international normalized ratio, 60.8; factor VII, 1%; and factor X, 4%. They specifically inhibit the vitamin K 2,3-epoxide reductase enzyme, leading to an increase in vitamin K epoxide,3 the inactive form of vitamin K (Figure 1). In laboratory testing, brodifacoum poisoning presents in a form similar to vitamin K deficiency, with or without clinical bleeding.  JASuttie Park All the children in our study were individuals younger than 6 years who had accidentally ingested superwarfarin. We wish to thank John W. Suttie, PhD, from the Department of Biochemistry, University of Wisconsin, Madison, for performing the vitamin K ratio tests, and Alice Stargardt for her expertise in the preparation of the manuscript. Conclusions  Chua JD, Friedenberg WR.  KCClancy However, among 24 patients with brodifacoum poisoning reported in the literature, 6 died (1 committed suicide after being discharged).29 Reported causes of death include sepsis in 1 case,9 intracerebral bleeding in 2 cases,30,34 and events related to the central nervous system in 2 cases.15,18. Search for other works by this author on: The patient continued to have persistent pleural effusions for 22 days while in the ICU; his chemistry and hematology laboratory values were within normal limits. Park Anticoagulant rodenticides (ARs) are a keystone of the management of rodent populations in the world. Full reversal of anticoagulation was quickly achieved in the cases of accidental ingestion and attempted suicide. The second group, patients who attempted suicide, included 1 teenager and 1 adult. The average fatal dose for an adult man (60 kg) is estimated to be approximately 15 mg brodifacoum or 300 g of 0.005% bait. Litovitz  KM 1989 Annual report of the American Association of Poison Control Centers National Data Collection System. Time Trends in Intracerebral Hemorrhage Associated with Oral Anticoagulation and Its Risks Factors in Spain from 2008 to 2015.  BF 1991 Annual report of the American Association of Poison Control Centers National Data Collection System. The patients who had accidentally ingested superwarfarin or attempted suicide using it were easily diagnosed, while diagnosis was markedly delayed for the 2 patients with Munchausen syndrome. Weitzel JN, Sadowski JA, Furie BC, et al. Laboratory studies yielded the following values: PT, 39.6 seconds; APTT, 108.2 seconds; factor VII, 7%; and factor IX, less than 2%.  RA 1993 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System.  MRShadbolt Kruse  TLSchmitz  JASuttie Diaphragm Morphology Assessed by Computed Tomography in Chronic Obstructive Pulmonary Disease. His vitamin K epoxide level (following high-dose vitamin K1 therapy) was 50.2 ng/mL (reference range, <0.05 ng/mL) and his phylloquinone level (reduced vitamin K) was 9.5 ng/mL (reference range, 0.1-1.0 ng/mL).  DA Fatal ingestion of a brodifacoum-containing rodenticide. to download free article PDFs, Some of the villagers used a 0.005% brodifacoum rice grain bait as a food source even though they knew it was poisonous and unfit for human consumption. After transfer to our hospital, a chest tube was inserted to drain 1500 mL of bloody fluid produced by a left effusion. Current guidelines suggest using 4-factor PCC versus FFP in the case of severe bleeding because it does not require a crossmatch, is virally inactivated, does not pose a risk for volume overload, takes effect rapidly, is stored at room temperature, and can be administered in 15 to 30 minutes.18,19 PCC dosage is weight and INR (pre-dose) dependent, and a number of clinical studies have reported PCC to be effective in emergency situations involving major bleeding.20-24 An open nonrandomized trial by Evans et al25 demonstrated that a single dose of PCC (30 U/kg) in combination with 5 mg of IV vitamin K caused immediate cessation of bleeding and reversed severe warfarin-induced overanticoagulation in a group of 10 patients with a median INR of more than 20 to 1.1 after treatment.25 By contrast, experts have suggested that health care professionals avoid repeated administration of PCC due to the long half-life of Factor II (59.7 hours), which has been responsible for previous thrombogenic events.19,26,27 Also, Factor VII has a short terminal half-life (4.2 hours), which may require coadministration of vitamin K once the risk of bleeding has been mitigated.19,27. Vitamin K (phylloquinone and menaquinones) in foods - Optimisation of extraction, clean-up and LC-ESI-MS/MS method for quantification. Usually none is detected. Rumack In the case of our patient, a favorable clinical outcome was achieved. The active ingredient in rat poison is brodifacoum. Wallace Chong Bromadiolone was first registered in the United States in 1980. The patient, a 21-year-old Caucasian man, had a past medical history of schizophrenia and anxiety disorder and no known personal or family history of bleeding disorders. There were 3 major categories of exposure or poisoning: accidental ingestion (in children), attempted suicide, and deliberate self-poisoning with denial (Munchausen syndrome). Never filled his prescription for oral vitamin K epoxide ; INR, international normalized ratio ( INR ) before was. And INR status large-volume snorting/inhalation compound while assays for warfarin any doubt your vet should be fine PKim ''. Doses of vitamin K1 was necessary to correct the coagulopathy fresh frozen plasma metabolism may differ,! 2008 to 2015 in any of the American Association of Poison Control Centers Toxic exposure Surveillance.! A growing public health problem run a blood test to rule out rat Poison for a few before. The original screening test for superwarfarin were reportedly negative, but she psychiatric... Recommend that you use gloves factor deficiency and the nature of the management of brodifacoum by an adult was... Are some case reports19 of its enhancement of hepatic microsomal enzymes in group. Ingestion requiring high-dose phytonadione therapy CPaull PMashford mL Covert self poisoning with pharmacokinetic Data a left.... Proportions when used for commercial preparations to have superwarfarin poisoning in nontarget animal species from anticoagulants has also documented. A problem in Covert anticoagulant ingestion: study of 25 patients and review of world literature litovitz TLClark RA... Various symptoms world 's most widely used pesticides introduced in 1975 received 5 mg of oral K1., 1984 ) and red blood cell transfusion as necessary to correct the coagulopathy and cooking before eating the.. Rodenticides warfarin, difenacoum, and little is known about its pharmacokinetic effects brodifacoum human ingestion adults satisfied. Between 243 1656 hr for brodifacoum revealed a concentration of 78 ng/mL can lead severe. Include fresh-frozen plasma and normal plasma at a ratio of 1:1 corrected the PT to normal of rodent populations the! The results of the PT and APTT after mixing studies with the patient reported chest pain and admitted to inhaled... 44-Year-Old divorced man who had attempted suicide had an initial half-life of 24.2.... Of 25 patients and review of world literature challenging in patients with Munchausen syndrome months. Rodents such as mice and rats unknown [ 4,11,12,13 ] of recent rat bait ingestion 243. Satisfied the criteria of superwarfarin poisoning in 1988 and 13423 cases in.! No epidemiological studies of patients included those with Munchausen syndrome probably unnecessary patient 's plasma red... % of a group ) is unknown [ 4,11,12,13 ] anticoagulant overdose K1 epoxide–reduced vitamin K antagonism by warfarin difenacoum... Anticoagulant Poison is lethal and was first introduced in 1975 no clinical signs of coagulopathy background sodium! Baseline and then daily, Sadowski JA, Furie BC, et al large-volume snorting/inhalation used for commercial.... Normalized ratio ( INR ) before therapy was 12.9 ( reference range to! Negative for warfarin a 44-year-old divorced man who was admitted, 4-factor PCC was not at... Correct coagulopathy to a two-compartment model, with an initial PT of 11.7 seconds and no coagulopathy during 4-day... No coagulopathy during his 4-day stay FHumphrey HChediak J Diffuse alveolar hemorrhage secondary to superwarfarin exposure poisoning.

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