A Case of Superwarfarin Intoxication without a Definitive History of Brodifacoum Exposure

Kim, Hyun; Han, Hye‐Suk; Lee, Ki Hyeong; Kim, Seung Taik

doi:10.5045/kjh.2009.44.1.53

Cited by 3 publications

(6 citation statements)

References 14 publications

(9 reference statements)

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“…Intoxication with superwarfarin rodenticides have to be considered for any patient with prolonged PT, aPTT, INR and decreased Vitamin K-dependent coagulation factors especially when INR fluctuates on Vitamin K therapy. [ 8 ] Liver dysfunction as a major cause of increased PT and INR and decreased Vitamin K-dependent coagulation factors was ruled out in our patient by normal liver enzymes, serum albumin concentration, and especially normal serum Factor V level as another coagulation factor that is synthesized by the liver. High consumption of coagulation factors (as seen in disseminated intravascular coagulopathy) was ruled out in our patient by high concentration of serum Factor VIII activity.…”

Section: Discussionmentioning

confidence: 92%

“…However, INR fluctuation on Vitamin K therapy as seen in our patient is well-reported in superwarfarin rodenticide intoxication even after a long-time after their consumption. [ 8 ] This case highlights the importance of caring old-aged patients especially who suffer dementia and cannot identify what they eat. They may be at risk for unaware intoxication.…”

Section: Discussionmentioning

confidence: 99%

“…[ 4 5 6 7 ] There is also a possible case of superwarfarin intoxication without a definite history of its exposure. [ 8 ] Here, we report a middle age man with dementia who was referred with epistaxis, epigastric pain and generalized ecchymosis. Whose family denied use of any drug or other substances by the patient, but health-care team was suspicious for intoxication with an anticoagulant agent.…”

Section: Introductionmentioning

confidence: 99%

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Possible unaware intoxication by anticoagulant rodenticide

et al. 2014

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Superwarfarin toxicity may be a serious problem. It needs high clinical suspicious in patients with bleeding diathesis without hematologic or liver diseases even in patients with apparent negative history of warfarin or other anticoagulant accessibility. Here we reported a patient with a negative history of any medical diseases or drug administration who was referred with generalized ecchymosis. Increased international normalized ratio and decreased vitamin K-dependent coagulation factors were detected in this patient. His hematologic and liver evaluations were normal. Clinical pharmacist emphasis in taking history revealed using anticoagulant rodenticide all over the farm the patient lived in that might result in unaware intoxication in this patient who suffered dementia.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Possible unaware intoxication by anticoagulant rodenticide

et al. 2014

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“…Only one patient (patient 6) lived in a metropolitan city, and outbreaks were nationwide. Most of the cases occurred since 2009, except for a male patient who diagnosed in 2007 ( 4 ). Two of them have been previously published as a case report ( 4 , 5 ).…”

Section: Resultsmentioning

confidence: 99%

Korean Patients with Superwarfarin Intoxication and Their Outcome

et al. 2010

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This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested.

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“…Brodifacoum has been widely used for the control of rodents since the mid-1970s (5,(14)(15)(16)(17)(18), and has a longer half-life in tissues than warfarin (19). The LD 50 for brodifacoum is 1 mg kg -1 or less in mammals (20), and only a single dose is needed for a lethal effect on rodents (21).…”

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confidence: 99%

Comparison of the effects of difenacoum and brodifacoum on the ultrastructure of rat liver cells

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et al. 2016

Archives of Industrial Hygiene and Toxicology

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We used transmission electron microscopy to examine the cytotoxic effects of the second-generation anticoagulant rodenticides difenacoum and brodifacoum on rat liver. A single dose of difenacoum or brodifacoum was administered to rats by gastric gavage and liver samples were taken after 24 h, four days or seven days. In the livers of rats treated with difenacoum for 24 h, hepatocytes typically showed increased numbers of lysosomes, as well as enlargement of both the perinuclear space and the cisternae of the rough endoplasmic reticulum (RER), while sinusoids were irregularly shaped and contained Kupffer cells. Similar irregularities occurred in brodifacoum-treated rats at the same time point, but additionally increased numbers of vacuoles, damaged mitochondrial cristae, and clumping of chromatin were observed in hepatocytes, and hemolysed erythrocytes were noted in the sinusoids. Comparable findings were made in each group of rats after four days. After seven days of difenacoum treatment, hepatocytes suffered loss of cytoplasmic material and mitochondrial shrinkage, while RER cisternae became discontinuous. In contrast, exposure to brodifacoum for seven days caused the formation of numerous vacuoles and lipid droplets, disordered mitochondrial morphology, chromatin clumping and invagination of the nuclear envelope in hepatocytes. Sinusoids in the livers of rodenticide-treated rats contained an accumulation of dense material, lipid droplets, cells with pycnotic nuclei and hemolysed erythrocytes. Overall, our results show that brodifacoum causes more severe effects in liver cells than difenacoum. Thus our microscopic data along with additional biochemical assays point to a severe effect of rodenticide on vertebrates.

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A Case of Superwarfarin Intoxication without a Definitive History of Brodifacoum Exposure

Cited by 3 publications

References 14 publications

Possible unaware intoxication by anticoagulant rodenticide

Possible unaware intoxication by anticoagulant rodenticide

Korean Patients with Superwarfarin Intoxication and Their Outcome

Comparison of the effects of difenacoum and brodifacoum on the ultrastructure of rat liver cells

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