Treatment experience of a case of brodifacoum poisoning / 中国职业医学

OBJECTIVE: To analyze the experience of diagnosis and treatment of a case of brodifacoum poisoning. METHODS: The clinical data of a case of unexplained brodifacoum poisoning was retrospectively analyzed. RESULTS: The patient went to the doctor for unexplained bleeding. The bleeding symptoms included nasal o blood ozing, blood in saliva and skin ecchymosis. Blood anticoagulative rodenticide test showed positive with brodifacoum. The results of coagulative function tests showed that the indexes of partial prothrombin time, prothrombin time and fibrinogen were increased. The patient was diagnosed as brodifacoum poisoning based on the clinical symptoms and laboratory test results. The combined use of 40 mg/d of vitamin K_1 and frozen plasma improved the clotting time and quickly alleviated the bleeding symptoms of the patient. However, the patient′s bleeding symptoms recurred when vitamin K_1 was discontinued. The patient was hospitalized for 62 days and then discharged. With follow-up one month after discharge, the patient showed no bleeding symptoms, but brodifacoum could still be detected in the blood. CONCLUSION: The symptoms of brodifacoum poisoning may relapse and the treatment course is long. Vitamin K_1 could be used as the first-choice medicine for the treatment of brodifacoum poisoning, but its usage needs to be optimized.

Evaluation of Brodifacoum-induced Toxicity by Metabonomics Approach Based on HPLC-TOF-MS / 法医学杂志

OBJECTIVES@#To analyse the metabolic changes in urine of rats with brodifacoum intoxication, and to reveal the molecular mechanism of brodifacoum-induced toxicity on rats.@*METHODS@#By establishing a brodifacoum poisoning rats model, the urine metabolic profiling data of rats were acquired using high performance liquid chromatography-time of flight mass spectrometry （HPLC-TOF-MS）. The orthogonal partial least squares analysis-discrimination analysis （OPLS-DA） was applied for the multivariate statistics and the discovery of differential metabolites closely related to toxicity of brodifacoum.@*RESULTS@#OPLS-DA score plot showed that the urinary metabolic at different time points before and after drug administration had good similarity within time period and presented clustering phenomenon. Comparing the urine samples of rats before drug administration with which after drug administration, twenty-two metabolites related to brodifacoum-induced toxicity were selected.@*CONCLUSIONS@#The toxic effect of brodifacoum worked by disturbing the metabolic pathways in rats such as tricarboxylic cycle, glycolysis, sphingolipid metabolism and tryptophan metabolism, and the toxicity of brodifacoum is characterized of accumulation effect. The metabonomic method based on urine HPLC-TOF-MS can provide a novel insight into the study on molecular mechanism of brodifacoum-induced toxicity.

Evaluation of Brodifacoum-induced Toxicity by Metabonomics Approach Based on HPLC-TOF-MS / 法医学杂志

Objective T o analyse the m etabolic changes in urine of rats w ith brodifacoum intoxication, and to reveal the m olecular m echanism of brodifacoum-induced toxicity on rats. Methods B y establish-ing a brodifacoum poisoning rats m odel, the urine m etabolic profiling data of rats w ere acquired using high performance liquid chromatography-timeofflightmassspectrometry (HPLC-TOF-M S).The orthogo-nal partial least squares analysis-discrim ination analysis (O PLS-D A ) w as applied for the m ultivariate statistics and the discovery of differential m etabolites closely related to toxicity of brodifacoum . Results O PLS-D A score plot show ed that the urinary m etabolic at different tim e points before and after drug adm inistration had good sim ilarity w ithin tim e period and presented clustering phenom enon. C om paring the urine sam ples of rats before drug adm inistration w ith w hich after drug adm inistration, tw enty-tw o m etabolites related to brodifacoum-induced toxicity w ere selected. Conclusion T he toxic effect of brodi-facoum w orked by disturbing the m etabolic pathw ays in rats such as tricarboxylic cycle, glycolysis, sphin-golipid m etabolism and tryptophan m etabolism , and the toxicity of brodifacoum is characterized of accu-m ulation effect. The m etabonom ic m ethod based on urine H PLC-TO F-M S can provide a novel insight into the study on m olecular m echanism of brodifacoum-induced toxicity.

Determination of five anticoagulant rodenticides in whole blood by high-performance liquid chromatography / 中国职业医学

OBJECTIVE: To establish a method for simultaneous detection of 5 anticoagulant rodenticides including brodifacoum, bromadiolone, flocoumafen, warfarin and difenacoum in whole blood by high-performance liquid chromatogarphy. METHODS: The 0. 5 m L of blood sample was extracted by 2. 0 m L ethyl acetate,then separated by Diamonsil C18 column( 250. 0 mm × 4. 6 mm × 5. 0 μm) using acid-ammonium acetate( 20. 0 mmol / L,p H = 5. 5) /methyl alcohol( 2∶ 8,V / V) as a mobile phase and detected by diode-array detector under the ultraviolet spectrum of 310 nm through high-performance liquid chromatogarphy. RESULTS: The good linear range of the 5 anticoagulant rodenticides was0. 50-10. 00 mg / L,and the correlation coefficients were > 0. 999 00. The detection limits of brodifacoum,bromadiolone,flocoumafen,warfarin and difenacoum were 0. 08,0. 06,0. 09,0. 04 and 0. 10 mg / L and the lower limits of quantitation were 0. 79,0. 58,0. 92,0. 45 and 0. 96 mg / L,respectively. The recovery rate was 98. 40%-104. 00%. The within-run relative standard deviation( RSD) was 0. 61%-7. 84%,and the between-run RSD was 1. 10%-9. 62%. The samples can be stored for 14 days in the refrigerator at 4 ℃. CONCLUSION: The method has advantages of simple operation,good separating effect,high sensitivity,precision and accuracy,which is suitable for detection of whole blood samples in rodenticide poisoning patients.

Evaluation of risk factors in patients with vitamin K-dependent coagulopathy presumed to be caused by exposure to brodifacoum

BACKGROUND/AIMS: Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin intoxication. METHODS: Seven patients with suspected superwarfarin intoxication who lacked any definitive history of rodenticide ingestion were included. Thirty-one patients initially diagnosed with rodenticide poisoning were also included. We performed a retrospective chart review of all subjects and examined clinical data including patient demographics and medical histories. RESULTS: Patients initially diagnosed with rodenticide poisoning were divided into two groups, one of which had a laboratory abnormality (prothrombin time [PT] > 13 seconds) and another group with PTs in the normal range. There was no significant difference between the two groups in any of age, gender, the extent of chronic alcohol consumption, the causative rodenticide, psychiatric problems, ingestion of drugs interacting with warfarin, the extent of intoxication, or the type of ingestion attempt. The albumin level of the former group was significantly lower than that of the latter group (p = 0.014). Furthermore, a significant difference between the two groups was evident in terms of simultaneous ingestion of rodenticide and alcohol (p = 0.023). CONCLUSIONS: Most patients with superwarfarin poisoning did not exhibit any complication. When such complications were evident, they were associated with serum albumin level and coingestion of rodenticide and alcohol.

Ingestão acidental de brodifacoum por um cão / Brodifacoum accidental ingestion by a dog

Produtos utilizados para controle de roedores ocupam a terceira posição entre as causas mais comuns de exposições a agentes tóxicos em cães. Cerca de 20% dessas exposições resultam em intoxicação (OSWEILER, 1998). A terapêutica adequada e o tempo decorrido entre a ingestão e os primeiros procedimentos são os principais fatores determinantes do sucesso do tratamento, o qual pode ocasionar distúrbios de coagulação e morte do paciente, se não for bem conduzido. Este trabalho relata um caso de ingestão acidental de brodifacoum por um cão e a subsequente abordagem terapêutica emergencial.

Korean Patients with Superwarfarin Intoxication and Their Outcome

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.

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

Superwarfarin intoxications that induce profound and prolonged coagulopathy are being increasingly reported, to such an extent that it is becoming a comparatively common intoxication. However, there have been few reported cases of superwarfarin intoxication with an inadvertent cause or an unknown origin. A 58-year-old man with recurrent painless hematuria was found to have an acquired deficiency of vitamin K dependent clotting factors, and a large amount of vitamin K was required to correct the coagulopathy. He had no history of warfarin use or any exposure to rodenticides, but brodifacoum was detected in his serum. It is important for physicians to be aware that significant coagulopathy can occur secondary to superwarfarin intoxication, without any known exposure to substances that might induce this.