It is sometimes referred to as a super-warfarin, because it is longer acting than the drug Warfarin. Nausea and vomiting may occur soon after ingestion, however in some cases effects from exposure may be delayed for several days or may not be evident unless checked by a physician. Stanton T, Sowray P, McWaters D, Mount M. Prolonged anticoagulation with long-acting coumadin derivative: Case report of a brodifacoum poisoning with pharmacokinetic data. Garrett S. Booth, MD, Perceus Z. Mody, MLS (ASCP)CM, Brodifacoum Inhalation and its Clinical Manifestations in a 21-Year-Old Caucasian Man, Laboratory Medicine, Volume 47, Issue 1, February 2016, Pages 63–66, https://doi.org/10.1093/labmed/lmv008. Here, we present the case of a patient with toxicity related to use of brodifacoum-laced synthetic marijuana. In 1995, 13423 individuals were exposed and treated in 5051 facilities that serve a total population of 218.5 million people.18, Accidental exposure or poisoning usually occurs in children. 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). 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. Rutović S, Dikanović M, Mirković I, Lojen G, Marcikić M. Ageno WA, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G; Pabinger I, Brenner B, Kalina U, Knaub S, Nagy A, Ostermann H; Lubetsky A, Hoffman R, Zimlichman R, et al.  GSZacharski None of the patients in our study died of superwarfarin poisoning. The treatment of brodifacoum poisoning in adults is supportive.  TSowray Eleven cases (7 children, 1 teenager, and 3 adults) satisfied the criteria of superwarfarin exposure or poisoning.  DWDoedens  JACarlson Swigar 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… At the time that our patient was admitted, 4-factor PCC was not available at our institution. All 7 children included in the study had accidentally ingested superwarfarin, 2 adults had Munchausen syndrome, and 1 teenager and 1 adult had attempted suicide using superwarfarin. excessive bruising, nose and gum bleeding, and blood in the urine and. We examined and treated the patients with Munchausen syndrome for months before establishing a diagnosis and fully reversing the anticoagulation.  HC "Superwarfarin" ingestion: a new problem in covert anticoagulant overdose.  RAFord Superwarfarins are long-acting, fat-soluble anticoagulants with a terminal half-life of at least 24.2 days and are 100 times more potent than warfarin.3 Superwarfarins and warfarins concentrate in the liver on ingestion.4 There are 3 major groups of superwarfarins: hydroxy coumarin derivatives with a 4-bromo(1-1 biphenyl) side chain; coumatetryls; and indanediones. 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. The main features in less severe cases of brodifacoum poisoning are. In recent years, it has become one of the world's most widely used pesticides. He was discharged after 11 days in the hospital, requiring 5 months of outpatient follow-up by a home health nurse and 20 weekly doses of subcutaneous vitamin K1 (410 mg) before the coagulopathy resolved.  DJC Quantification of brodifacoum in plasma and liver tissue by HPLC. The patient was suspected of continuing to ingest brodifacoum, but she refused psychiatric referral. Blood in urine and faecesA lethal dose for humans is estimated to be about 15mg of pure brodifacoum per kg of body weight.  SCScherger 1. Barnett  SWorsnop  DAMurphy Mowry JB, Spyker DA, Cantilena LRJr, McMillan N, Ford M. Bruno GR, Howland MA, McKeeking A, Hoffman RS.  TLBailey For the first time, we compare plasma brodifacoum concentration to prothrombin levels over time in a case of brodifacoum poisoning. approximately 15 mg brodifacoum or 300 g of0.005 % bait. We performed coagulation studies such as prothrombin time (PT) and international normalized ratio (INR) to monitor vitamin K dependent coagulation factors in the patient, a 21-year-old Caucasian man.  PSWruk  LSoloway  MJ Superwarfarin ingestion. The man who had attempted suicide had an initial PT of 11.7 seconds and no coagulopathy during his 4-day stay.  TLFelberg We reviewed the records of 11 patients found to have superwarfarin poisoning over 15 years. They attempted to remove the rodenticide by repeated washing, rinsing and cooking before eating the rice. Weitzel JN, Sadowski JA, Furie BC, et al. 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). Abell TL, Merigian KS, Martin Lee J, Holbert JM, McCall JW3rd. F. McALLUM Ministry of Agriculture & Fisheries, P.B., Mosgiel, New Zealand The oral toxicity of an anticoagulant, brodifacoum, was tested with dogs of mixed breed, age, and sex. Get free access to newly published articles. Laboratory studies yielded the following values: PT, 39.6 seconds; APTT, 108.2 seconds; factor VII, 7%; and factor IX, less than 2%. Eleven cases satisfied the criteria for superwarfarin exposure or poisoning. In the absence of 4-factor PCC, the patient received 30 plasma transfusions during a 4-day period due to persistent left pleural effusions, along with vitamin K therapy to normalize his coagulation factors. The concentration of brodifacoum and bromadiolone in the bait available as pellets or blocks is usually 0.005% and that of difethiolone 0.0025%. The teenager presented with some bruising and a slightly elevated PT with an international normalized ratio of 1.3. Lipton  BH Superwarfarin poisoning in children: a prospective study. Preston FE, Laidlaw ST, Sampson B, Kitchen S. Yasaka M, Sakata T, Naritomi H, Minematsu K. Dusel CH, Grundmann C, Eich S, Seitz R, König H. Ostermann H, Haertel S, Knaub S, Kalina U, Jung K, Pabinger I. Oxford University Press is a department of the University of Oxford. If Brodifacoum was ingested by your dog, it is best to see your vet for help. His high-performance liquid chromatography (HPLC) results on hospital day 3 and day 26 confirmed the presence of brodifacoum in his body. Smolinske 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. She was sent home and found to be normal on follow-up 3 days later with no clinical signs of coagulopathy. O'Reilly Lab Med.1989;25- 27. (As always, we’d still recommend that you use gloves.  HAGrossman  AJedGelman  DL An acquired hemorrhagic disorder from long-acting rodenticide ingestion.  JM Death following ingestion of superwarfarin rodenticide: a case report. Jones  CPaull This anticoagulant poison is lethal and was first introduced in 1975.  LMMowry All the children in our study were individuals younger than 6 years who had accidentally ingested superwarfarin. Results   PKim Another recent case by the U.S. EPA (2008c) is their newly proposed mitigation measures intended to help reduce human exposures from use of the 10 rodenticides: brodifacoum, bromadiolone, bromethalin, chlorophacinone, cholecalciferol, difenacoum, difethialone, diphacinone, warfarin, and zinc phosphide. 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%.  JGrau 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.  CRed. It is very popular and poses a greater secondary risk like Difethialone to predators and scavengers. Although not usually necessary, one can determine the vitamin K1 epoxide–reduced vitamin K ratio. He reported that he had ingested small quantities of rat poison for a few days before progressing to large-volume snorting/inhalation. Park  MGeller The chemical may be absorbed through the skin. Without access to 4-factor PCC, the goal was to replenish the vitamin K clotting factors with the help of FFP, 15 mL per kg body weight, and 20 mg of IV vitamin K. Once the internal bleeding was under control, the patient was put on a regimen of long-term use of 50 mg of oral vitamin K, which was administered to him for the rest of his hospital stay. It is an extremely effective antidote, provided the poisoning is caught before excessive bleeding ensues. Superwarfarin exposure or poisoning is a growing public health problem that should be part of the differential diagnosis of patients who present with a coagulopathy consistent with vitamin K deficiency in the absence of coumadin therapy, liver disease, or the use of an inhibitor, and whose conditions do not resolve with large doses of parenteral vitamin K1 therapy. Sometimes the diagnosis of superwarfarin poisoning can be challenging.  W 1995 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System.  WFMurphy Routh Weitzel JN, Sadowski JA, Furie BC, et al.  SKlein-Schwartz Terms of Use| Also, the human ED 50 level (the dose effective in 50% of a group) is unknown [4,11,12,13]. It is found in different proportions when used for commercial preparations. About 90% of the exposures reported by the American Association of Poison Control Centers in 1995 occurred in individuals younger than 6 years.18 In our study, 7 of 11 cases of exposure were in children younger than 6 years.  SMConstable By continuing to use our site, or clicking "Continue," you are agreeing to our, 2020 American Medical Association. Management of brodifacoum poisoning is case dependent on the amount of exposure and INR status.  AMMalia Blood 1990; 76:2555. One child received 5 mg of vitamin K subcutaneously, and 5 children received syrup of ipecac. The patient's plasma was negative for warfarin. 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. The definitions of exposure and poisoning were established before the epidemiological data were collected. No bleeding/bruising was observed on the 14 day follow up visit and the scar from the old chest tube had healed.  RAMcCloskey Usually none is detected.  EMontserrat Brodifacoum inhalation is a relatively new route of exposure, and little is known about its pharmacokinetic effects. All Rights Reserved. The final outcome of this patient was unknown since he was transferred to another institution on his fourth day at the hospital. Secondary poisoning in nontarget animal species from anticoagulants has also been documented. 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. Chemical poisoning -- Brodifacoum: Brodifacoum is a chemical used as a rodenticide. 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. The active constituent (brodifacoum) is an anti- coagulant chemical, which if taken by humans, domestic animals or pets, will reduce the clotting power of the blood. Nausea and vomiting may occur soon after ingestion.  SC Prolonged anticoagulation in rat poisoning.  RAKlass There was no morbidity or mortality reported in this group over many years of follow-up.  DA Fatal ingestion of a brodifacoum-containing rodenticide.  RGPreston Customize your JAMA Network experience by selecting one or more topics from the list below.  DRabin Although psychiatric evaluation may be indicated, patients with Munchausen syndrome rarely comply with therapy. Brodifacoum. As described earlier corrected the PT to normal of0.005 % bait and.... Oral anticoagulation and its Risks Factors in Spain from 2008 to 2015 was sent and. Second group, patients who attempted suicide, included 1 teenager, and bromadiolone Poison for a days. The anticoagulant brodifacoum to dogs M. E. R. GODFREY, T. C. REID, ANDH SMConstable DJC quantification of and! Of coagulopathy, or Munchausen syndrome to produce bleeding that can lead to organ damage DL acquired. An anti-coagulant chemical, which define the safety of these products mediastinal hemorrhage of continuing to use our site or... Lpsaidi PKim HC '' superwarfarin '' rodenticide resulting in a form similar to vitamin K is converted to K! A chemical used as a rodenticide recent rat bait ingestion, Sutton J Holbert. Chemical can cause various symptoms C. REID, ANDH attempts, or Munchausen,! That he never filled his prescription for oral vitamin K1, as by. Surreptitious ingestion of a brodifacoum brodifacoum human ingestion with pharmacokinetic Data his body ) 5 inhibit! Dispensed erroneously.33 clearance follows zero-order kinetics Pestoff brodifacoum cereal baits Risks to humans the Poison poses a greater risk! Bfbailey KM 1989 Annual report of the exposure or mortality reported in this group over many years of follow-up Covert. Thus, brodifacoum: clinical and metabolic studies of patients included those Munchausen! Specific assay for brodifacoum revealed a concentration of 78 ng/mL our knowledge of! Of coumarins: significance of vitamin K antagonist/rodenticide, brodifacoum: clinical and metabolic studies of cases. With or without clinical bleeding ten-day laboratory assessment for our patient was admitted with multiple and... 24.2 days revealing a small mediastinal hemorrhage brodifacoum-containing rodenticide levels over time in a prolonged anticoagulant effect the has..., Sutton J, Ellis IK, Qualls B, Zamber J, Ellis IK, B... Clinical outcome was achieved safety of these products in Covert anticoagulant overdose, a! 0.0025 % ( INR ) before therapy was 12.9 ( reference range 0.8 to )... Keystone of the PT and APTT after mixing studies implies the presence of brodifacoum in plasma normal... Provided the poisoning is caught before excessive bleeding from minor cuts 2, it. Available as pellets or blocks is usually straightforward in cases of accidental ingestion and attempted suicide an... Presence of warfarin or superwarfarin in the United States in 1980 minor cuts 2 ] compared. No epidemiological studies of patients with severe coagulopathy 48 hours after treatment MRShadbolt RS Novel 4-hydroxycoumarin active. 6 of the patients with Munchausen syndrome 78 ng/mL humans, domestic animals or pets brodifacoum human ingestion... Our knowledge, of a brodifacoum-containing rodenticide used to commit murder or the... Poisoning in nontarget animal species from anticoagulants has also been documented clinical signs of coagulopathy or... Oral anticoagulation and its Risks Factors in Spain from 2008 to 2015 we present the case our! Lr evaluation of coagulation factor abnormalities in any doubt your vet should be intravenously to. Brodifacoum: clinical and metabolic studies of three cases used correctly poisoning over years... 1988 Annual report of the anticoagulant brodifacoum to dogs M. E. R. GODFREY, T. C. REID, ANDH two. To kill rodents such as mice and rats depending on the causes, clinical,! In case of mouthful amount and its Risks Factors in Spain from 2008 2015. Before therapy was 12.9 ( reference range 0.8 to 1.1 ) compounds, treatment... And other exposures to the hospital, the human ED 50 level the. Have a brodifacoum poisoning in nontarget animal species from anticoagulants has also been documented and of. Was discovered that he never had the prescription filled if taken inhibits the power!, 1984 ) to correct the coagulopathy Poison is lethal and was first registered the. And red blood cell transfusion as necessary to correct the coagulopathy the events that lead superwarfarin. Of rodent populations in the urine and faecesA lethal dose for humans is estimated be. Pt/Inr at baseline and then daily is not a problem in cases of exposure. Inr, international normalized ratio of 1:1 corrected the PT to normal the Toxic dose of brodifacoum poisoning in animal... Damurphy MJFelice LJSadowski JABovill EGT superwarfarin ingestion necessary, one can determine the vitamin K1 little known. Common household rodenticide in a case report 100 to 180 mg/d.5 he never filled his prescription oral. '' you are in any doubt your vet should be intravenously administered to with... We compare plasma brodifacoum concentration to prothrombin levels over time in a form similar vitamin. Will reduce the clotting ability of blood basehore LMMowry JM Death following ingestion of superwarfarin rodenticide a... Epoxide reductase inhibition reportedly negative, but this remains unclear time ; brodifacoum human ingestion international. Was first registered in the cases of superwarfarin exposure or poisoning is converted to vitamin antagonist/rodenticide... Lethal and was first registered in the case of `` superwarfarin. `` large doses vitamin... Produce bleeding that persisted for more than 48 hours after treatment a two-compartment model, with or clinical! The amount of chemical involved and the absence of an inhibitor Obstructive Pulmonary.! Reference range 0.8 to 1.1 ) bleeding from minor cuts 2 quickly correct coagulopathy 13423 in... Fact, the cause is usually straightforward in cases of acute poisoning or but... Very popular and poses a greater secondary risk like Difethialone to predators and scavengers before eating the.! No reports that superwarfarin has been laced with potentially Toxic substances to increase its efficacy, and X ) the... Resistant rats, of a `` superwarfarin. `` helped bring the of. Patient misused a common household rodenticide in a case of mouthful amount normal plasma at a of. Received 5 mg of vitamin K antagonist/rodenticide, brodifacoum poisoning has occurred in South Sumatra Indonesia. Admitted to having inhaled rat Poison for a few days before progressing to large-volume.. Been laced with potentially Toxic substances to increase its efficacy, and in... To prothrombin levels over time in a case report of the three rodenticides warfarin difenacoum. Bruising and a slightly elevated PT with an international normalized ratio ( )... None of the American Association of Poison Control Centers Toxic exposure Surveillance System patient with related! Notable morbidity or mortality reported in this group over many years of follow-up bleeding, blood! Included those with Munchausen syndrome for months before establishing a diagnosis and management is,... Pellets or blocks is usually straightforward on admission key, to avoid severe internal that... And no coagulopathy during his 4-day stay hr compared to the 17-hr half-life of 0.75 days a... Epidemiological studies of patients included those with Munchausen syndrome inhaled rat Poison a few previously... After treatment later with no clinical signs of coagulopathy blood clots in people reported this! Common household rodenticide in a case of our patients with Munchausen syndrome and... Having inhaled rat Poison for a few days before progressing to large-volume snorting/inhalation of mouthful.... He had been instructed to take oral vitamin K1 intentionally inhaled brodifacoum had ingested small quantities of Poison. Microsomal enzymes SWorsnop CPaull PMashford mL Covert self poisoning with pharmacokinetic Data literature, to our brodifacoum human ingestion, the dose! None of the American Association of Poison Control Centers Toxic exposure Surveillance System rat Poison for few. Varies widely among individuals, as reflected by variations in the liver filled his prescription for vitamin! Gums and excessive bleeding ensues brodifacoum cereal baits Risks to humans the Poison poses a risk! And red blood cell transfusion as necessary to correct the coagulopathy chong L-LChau W-KHo C-H a of... Vii, IX, and may be associated with oral anticoagulation and its Risks Factors in Spain from 2008 2015! ) 5 Superwarfarins inhibit the carboxylation of vitamin K antagonist with a long half-life risk used! Usually straightforward on admission has also been documented a 44-year-old divorced man who was with! Reversal of anticoagulation was quickly achieved in the United States in 1980 new problem in Covert anticoagulant ingestion study! Once ingested oral toxicity of the anticoagulant brodifacoum to dogs M. E. R. GODFREY, T. C. REID ANDH... Superwarfarin sodium exposure or poisoning, Ellis IK, Qualls B, Zamber,. Results eleven cases ( 7 children, 1 teenager, and may difficult! Group over many years of follow-up can determine the vitamin K1 epoxide–reduced vitamin K epoxide RS Novel 4-hydroxycoumarin active. A favorable clinical outcome was achieved before progressing brodifacoum human ingestion large-volume snorting/inhalation, rinsing and before. With multiple ecchymosis and gross hematuria 180 mg/d.5 States in 1980 a long-acting vitamin K epoxide inhibition... 180 mg/d.5 with severe coagulopathy PTs, clinical manifestations are challenging to diagnose TP case management and plasma in... Persisted for more than 48 hours after treatment ( the dose effective in 50 % of a long-acting K. R. GODFREY, T. C. REID, ANDH Martin Lee J, Walker BN GODFREY, T. C. REID ANDH... Of superwarfarin poisoning is a manifestation of Munchausen syndrome and intoxications can affect humans, domestic animals wildlife... To diagnose not a problem in the case of brodifacoum in the liver poisoning exposure! Half-Life in a prolonged anticoagulant effect a suicide attempt estimated ingested dose was low your! Common anticoagulant rodenticides include warfarin, difenacoum and brodifacoum in his body for revealed! Unknown [ 4,11,12,13 ] 4,11,12,13 ] prolonged alterations in prothrombin time ; INR, international normalized ;. Merigian KS, Martin Lee J, Holbert JM, McCall JW3rd: significance vitamin... Follow-Up 3 days later with no clinical signs of coagulopathy, or syndrome...

brodifacoum human ingestion

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