Persistent Coagulopathy After Synthetic Cannabinoid Use.

Synthetic cannabinoids (SCs) are chemical compounds created and manufactured, without quality control standards or requirements, to mimic tetrahydrocannabinol (THC). They are widely available in the USA, and they are sold under various brand names, including "K2" and "spice." Many adverse effects have been attributed to SCs, but most recently, they have also been associated with bleeding. There have been reported cases around the globe of SCs contaminated with long-acting anticoagulant rodenticide (LAAR) or superwarfarins. They are developed from compounds such as bromethalin, brodifacoum (BDF), and dicoumarol. LAAR exhibits their mechanism as a vitamin K antagonist inhibiting vitamin K 2,3-epoxide reductase, preventing activation of vitamin K1 (phytonadione). Therefore, reducing the activation of clotting factors II, VII, IX, and X and proteins C and S. In contrast to warfarin, BDF has an extremely long-acting biological half-life of 90 days due to minimal metabolism and limited clearance. Here, we report a 45-year-old male who presented to the emergency room with a 12-day history of gross hematuria and mucosal bleeding without previous history of coagulopathy and recurrent SCs use.

Chiral liquid chromatography-tandem mass spectrometry analysis of superwarfarin rodenticide stereoisomers - Bromadiolone, difenacoum and brodifacoum - In human plasma.

Superwarfarins are second-generation long-acting anticoagulant rodenticides that can cause unintended human and wildlife toxicity due, in part, to their prolonged half-lives. Commercially available superwarfarin rodenticides are synthesized as racemates with two asymmetric carbons, producing four stereoisomers. To support studies of human plasma half-lives of individual superwarfarin stereoisomers, a method was developed based on LC-MS/MS to separate and quantify stereoisomers of the commercially important superwarfarins bromadiolone, difenacoum and brodifacoum. Human plasma samples were prepared using protein precipitation and centrifugation. Chiral-phase HPLC separation was carried out on-line with tandem mass spectrometric quantitative analysis of the eluting stereoisomers using selected-reaction monitoring with positive ion electrospray on a triple quadrupole mass spectrometer. All four stereoisomers of each superwarfarin were resolved within 12.5 min with calibration curves spanning 2-3 orders of magnitude and lower limits of quantitation between 0.87 and 2.55 ng/mL. This method was used to determine the half-lives of superwarfarin stereoisomers in plasma from patients who had inhaled synthetic cannabinoid products contaminated with superwarfarins. These data may be used to guide the development of safer next generation anticoagulant rodenticides stereoisomers.

Acute toxic encephalopathy following bromadiolone intoxication: a case report.

BACKGROUND: Clinically, bromadiolone poisoning is characterized by severe bleeding complications in various organs and tissues. Bromadiolone-induced toxic encephalopathy is extremely rare. Here, we report a special case of bromadiolone-induced reversible toxic encephalopathy in a patient who had symmetrical lesions in the deep white matter. CASE PRESENTATION: A 23-year-old woman mainly presented with dizziness, fatigue, alalia and unsteady gait after the ingestion of bromadiolone. The laboratory examinations showed normal coagulation levels. Brain magnetic resonance imaging (MRI) showed apparent diffusion restriction in the bilateral deep white matter. The clinical manifestations and MRI alterations were reversible within one month of treatment with vitamin K. The neuropsychological assessment showed no neurodegenerative changes at the 2-year follow-up. CONCLUSION: With the increased use of bromadiolone as a rodenticide, more cases of ingestion have been reported annually over the past several years. Bromadiolone-induced toxic encephalopathy has no special clinical manifestations and is potentially reversible with timely treatment. Because of the reversible restricted diffusion on diffusion-weighted images (DWI) and low apparent diffusion coefficient (ADC) values, transient intramyelinic cytotoxic oedema is thought to be the cause rather than persistent ischaemia. The underlying pathophysiological mechanism is still unknown and may be coagulant-independent. This clinical case extends the current knowledge about neurotoxicity in cases of bromadiolone poisoning and indicates that MRI is useful for the early detection of bromadiolone-induced toxic encephalopathy.

Sudden nasal bleeding and brodifacoum: A case of accidental exposure or attempted homicide?

A 50-year-old man was admitted to the emergency department with abrupt massive epistaxis. An accurate anamnesis and physical evaluation could not reveal any other anomalies, while coagulation tests showed potentially life threatening prolonged prothrombin time, with activated partial thromboplastin and thrombin time, with fibrinogen and antithrombin III within limits. Despite the prompt pharmacological and compressive local treatment, bleeding continued and the patient was therefore hospitalized. Highly specific coagulation and toxicological testing-among others high-performance liquid chromatography assessment on plasma-were performed, leading to the unexpected identification of brodifacoum. Police and criminal justice authorities revealed the source of exposure to brodifacoum after several months of investigation, residing in his everyday life. Brodifacoum is a long-lasting anticoagulant, acting as a vitamin K antagonist, and belongs to the family of superwarfarins. Brodifacoum use is authorized as rodenticide in many countries worldwide, but has been reported as cause of severe coagulopathies in humans, both intentional or involuntary, even consumed as a contaminant of herbal drugs, such as cannabis. The original contribution of this case to the knowledges of human brodifacoum intoxication resides in the multidisciplinary approach and the collaborative interplay of clinical and toxicology experts as well as judicial authorities.

In silico evaluation of pesticides as potential modulators of human DNA methyltransferases.

DNA methylations are carried out by DNA methyltransferases (DNMTs) that are key enzymes during gene expression. Many chemicals, including pesticides, have shown modulation of epigenetic functions by inhibiting DNMTs. In this work, human DNMTs were evaluated as a potential target for pesticides through virtual screening of 1038 pesticides on DNMT1 (3SWR) and DNMT3A (2QRV). Molecular docking calculations for DNMTs-pesticide complexes were performed using AutoDock Vina. Binding-affinity values and contact patterns were employed as selection criteria of pesticides as virtual hits for DNMTs. The best three DNMT-pesticides complexes selected according to their high absolute affinity values (kcal/mol), for both DNMT1 and DNMT3A, were flocoumafen (-12.5; -9.9), brodifacoum (-12.4; -8.4) and difenacoum (-12.1; -8.7). These chemicals belong to second-generation rodenticides. The most frequent predicted interacting residues for DNMT1-pesticide complexes were Trp1170A, Phe1145A, Asn1578A, Arg1574A and Pro1225A; whereas for DNMT3A those were Arg271B, Lys740A, and Glu303B. These results suggest that rodenticides used for pest control are potential DNMT ligands and therefore, may modulate DNA methylations. This finding has important environmental and clinical implications, as epigenetic pathways are critical in many biochemical processes leading to diseases.

Brodifacoum does not modulate human cannabinoid receptor-mediated hyperpolarization of AtT20 cells or inhibition of adenylyl cyclase in HEK 293 cells.

BACKGROUND: Synthetic cannabinoids are a commonly used class of recreational drugs that can have significant adverse effects. There have been sporadic reports of co-consumption of illicit drugs with rodenticides such as warfarin and brodifacoum (BFC) over the past 20 years but recently, hundreds of people have been reported to have been poisoned with a mixture of synthetic cannabinoids and BFC. We have sought to establish whether BFC directly affects cannabinoid receptors, or their activation by the synthetic cannabinoid CP55940 or the phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC). METHODS: The effects of BFC on the hyperpolarization of wild type AtT20 cells, or AtT20 cells stably expressing human CB1- or CB2- receptors, were studied using a fluorescent assay of membrane potential. The effect of BFC on CB1- and CB2-mediated inhibition of forskolin-stimulated adenylyl cyclase (AC) activation was measured using a BRET assay of cAMP levels in HEK 293 cells stably expressing human CB1 or CB2. RESULTS: BFC did not activate CB1 or CB2 receptors, or affect the hyperpolarization of wild type AtT20 cells produced by somatostatin. BFC (1 µM) did not affect the hyperpolarization of AtT20-CB1 or AtT20-CB2 cells produced by CP55940 or Δ9-THC. BFC (1 µM) did not affect the inhibition of forskolin-stimulated AC activity by CP55940 in HEK 293 cells expressing CB1 or CB2. BFC (1 µM) also failed to affect the desensitization of CB1 and CB2 signaling produced by prolonged (30 min) application of CP55940 or Δ9-THC to AtT20 cells. DISCUSSION: BFC is not a cannabinoid receptor agonist, and appeared not to affect cannabinoid receptor activation. Our data suggests there is no pharmacodynamic rationale for mixing BFC with synthetic cannabinoids; however, it does not speak to whether BFC may affect synthetic cannabinoid metabolism or biodistribution. The reasons underlying the mixing of BFC with synthetic cannabinoids are unknown, and it remains to be established whether the "contamination" was deliberate or accidental. However, the consequences for people who ingested the mixture were often serious, and sometimes fatal, but this seems unlikely to be due to BFC action at cannabinoid receptors.

Sugar, Spice, and Bleeding.

Brodifacoum (BDF), otherwise known as superwarfarin, is a long-acting anticoagulant rodenticide (LAAR) which acts as a vitamin K antagonist. Much like warfarin, BDF's mechanism of action is to irreversibly inhibit the enzyme vitamin K epoxide reductase, thus reducing the recycling of vitamin K and, therefore, reducing the activation of clotting factors two, seven, nine, and 10. Although BDF is usually found in rodenticides, it has been recently used as an additive in synthetic cannabinoids. We present a case of a young male with a history of synthetic cannabinoid use who presented with hematuria and epistaxis and was ultimately found to have BDF poisoning.

Superwarfarin Exposure: An Important Uncommon Cause of Painless Bleeding.

Painless bleeding in a patient presenting from the community with elevated coagulation studies rarely makes the physicians suspect superwarfarin or rodenticide poisoning. Although a significant number of superwarfarin exposure cases are diagnosed every year, we believe there appears to be delay in diagnosis and confusion in determining what is the ideal way to treat and monitor these patients during the management. This is the first thorough literature review of all the reported cases of superwarfarin poisoning which also studied the clinical presentation, management and follow-up patterns. We present a 70-year-old man who presented to the emergency room with epistaxis, melena, cola-colored urine with elevated prothrombin time (PT), activated partial thromboplastin time (aPTT) and international normalized ratio (INR). Mixing studies showed complete correction of coagulopathy indicative of factor deficiency. Additional history revealed that the patient had arguments with family member at home and made us suspect superwarfarin exposure. Qualitative brodifacoum testing was positive and was managed with fresh frozen plasma and high doses of vitamin K1 (phytomenadione) with serial monitoring of INR and clinical symptoms. Superwarfarin poisoning should be considered in the differential diagnosis of a patient who presents with above clinical and laboratory profile especially in the absence of any history of coagulopathy or anticoagulant use. We want to raise public and especially physician awareness that history taking, early diagnosis and managing in right clinical setting play a significant role in survival of these patients.

Treatment for long acting anticoagulant rodenticide poisoning - beyond INR monitoring?

Poisoning by long acting anti-coagulant rodenticides (LAARs) requires long-term treatment with oral vitamin K1 (VK1). However, discontinuing treatment based on normalization of INR, may leave some patients with serum LAAR concentrations above a level considered safe. To address this, we carried out a retrospective analysis of 21 case reports of LAAR poisoning having at least two serum LAAR concentrations quantified during treatment with oral VK1. We identified the case reports by survey of existing peer-reviewed literature in which a patient presented to emergency department exhibiting bleeding or elevated INRs, and had quantitative measurements of serum LAAR concentrations. Of 21 case reports, measurement of serum LAAR concentrations following VK1 treatment showed that over half (n=11) had serum LAAR concentrations that were above a concentration considered to be safe (10 ng/mL), despite having received higher daily and total VK1 dosing, over an equivalent treatment duration. Since residual amounts of serum and tissue LAAR could contribute to symptom recurrence and repeated hospitalization, these results indicate that normalization of INR is not a sufficient criterion to discontinue VK1 treatment and that measurements of serum LAAR concentrations should be included to help guide decisions to continue or discontinue VK treatment.

Effects of bromadiolone poisoning on the central nervous system.

Cases of rodenticide poisoning (second-generation long-acting dicoumarin rodenticide, superwarfarin) have occasionally been reported. The main symptoms of bromadiolone poisoning are skin mucosa hemorrhage, digestive tract hemorrhage, and hematuresis. However, the symptoms of central nervous system toxicity have rarely been reported. Our case reports on a 41-year-old male who had no contact with bromadiolone. His main symptoms were dizziness, unsteady gait, and abnormal behavior. Laboratory test results revealed the presence of bromadiolone in his blood and urine, a longer prothrombin time, activated partial thromboplastin time, and a high international normalized ratio. Magnetic resonance imaging of the brain showed that the bilateral posterior limb of the internal capsule, splenium of corporis callosum, and bilateral centrum semiovale formed symmetrical patch distribution. The patient gradually recovered after treated with vitamin K1 and plasma transfusion. Our clinical study could pave the way to improve the detection of bromadiolone poisoning and avoid misdiagnosis.

Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment courses averaged 168 days. Adjunctive hemostatic therapy with recombinant factor VIIa and prothrombin complex concentrate has been reported, and phenobarbital has been used to expedite LAAR metabolism.

Intoxicaciones con rodenticidas superwarfarínicos / Superwarfarin rodenticide poisoning

Introducción: en la actualidad existe utilización masiva de rodenticidas y su venta no está restringida al público. Las etiologías de intoxicación por estos agentes son variadas pudiendo ser de tipo intencional o accidental. Objetivo: analizar estudios realizados en torno a intoxicaciones con rodenticidas superwarfarínicos en humanos con el propósito de reunir información que oriente a un adecuado tratamiento. Metodología: se realizó una revisión integradora en las bases de datos electrónicas PubMed, TripDataBase, Cochrane, además de Google Scholar y SciELO, libros de divulgación científica, documentos de convenciones, páginas web de instituciones públicas, privadas y artículos vinculados a efectos, cuadro clínico y tratamiento de exposiciones a rodenticidas en seres humanos. Se analizaron los documentos y la información se organizó en tres temáticas: toxicidad de los rodenticidas superwarfarínicos, cuadro clínico y tratamiento médico, y rodenticidas no anticoagulantes disponibles en Chile. Resultados: la dosis tóxica mínima reportada en adultos es de 1 mg de principio activo; en pacientes pediátricos ingestas accidentales rara vez producen síntomas. Los síntomas se observan de forma tardía y su toxicidad es variable. El examen de elección es el International Normalized Ratio (INR) y se realiza en todo paciente con factores de riesgo presentes. El antídoto no se administra de forma profiláctica y la dosis se ajusta individualmente. Conclusión: en niños las ingestas accidentales no son riesgosas por lo que pueden ser observados en el hogar. Pacientes con ingestas masivas requieren controles de INR por meses por lo que es importante que posterior al alta médica exista una óptima coordinación con nivel primario de atención.(AU)

Introduction: Currently there is a widespread use of rodenticides, unrestricted to the public. The exposure to these agents may varied being intentional or accidental. Objective: To analyze studies about superwarfarin poisoning in humans, with the purpose of gathering information to guide proper treatment. Methodology: It was conducted an integrative review in the electronic databases PubMed, TripDataBase, Cochrane, Google Scholar and SciELO, science books (reference textbooks), convention documents, websites from public and private institutions and articles about the effects, clinical manifestations and treatment of human exposures to rodenticides. Documents were analyzed and the information organized into three themes: superwarfarin toxicity, clinical features and medical treatment, and non-anticoagulant rodenticides available in Chile. Results: In adults, the minimum dose reported to cause toxicity is 1 mg of active ingredient. In pediatric patients, accidental intakes rarely produce symptoms. The symptoms of poisoning are usually delayed and its toxicity is variable. The test of choice is International Normalized Ratio (INR) and it is performed in all patients with risk factors. The antidote must not be administered prophylactically and the dose is adjusted individually. Conclusions: Accidental intakes in children are not risky and they can be observed at home. Patients with massive intakes require INR monitoring for months so, it is important that an optimal coordination with primary care facilities still exists after medical discharge.(AU)

Intoxicaciones con rodenticidas superwarfarínicos / Superwarfarin rodenticide poisoning

Introducción: en la actualidad existe utilización masiva de rodenticidas y su venta no está restringida al público. Las etiologías de intoxicación por estos agentes son variadas pudiendo ser de tipo intencional o accidental. Objetivo: analizar estudios realizados en torno a intoxicaciones con rodenticidas superwarfarínicos en humanos con el propósito de reunir información que oriente a un adecuado tratamiento. Metodología: se realizó una revisión integradora en las bases de datos electrónicas PubMed, TripDataBase, Cochrane, además de Google Scholar y SciELO, libros de divulgación científica, documentos de convenciones, páginas web de instituciones públicas, privadas y artículos vinculados a efectos, cuadro clínico y tratamiento de exposiciones a rodenticidas en seres humanos. Se analizaron los documentos y la información se organizó en tres temáticas: toxicidad de los rodenticidas superwarfarínicos, cuadro clínico y tratamiento médico, y rodenticidas no anticoagulantes disponibles en Chile. Resultados: la dosis tóxica mínima reportada en adultos es de 1 mg de principio activo; en pacientes pediátricos ingestas accidentales rara vez producen síntomas. Los síntomas se observan de forma tardía y su toxicidad es variable. El examen de elección es el International Normalized Ratio (INR) y se realiza en todo paciente con factores de riesgo presentes. El antídoto no se administra de forma profiláctica y la dosis se ajusta individualmente. Conclusión: en niños las ingestas accidentales no son riesgosas por lo que pueden ser observados en el hogar. Pacientes con ingestas masivas requieren controles de INR por meses por lo que es importante que posterior al alta médica exista una óptima coordinación con nivel primario de atención.

Introduction: Currently there is a widespread use of rodenticides, unrestricted to the public. The exposure to these agents may varied being intentional or accidental. Objective: To analyze studies about superwarfarin poisoning in humans, with the purpose of gathering information to guide proper treatment. Methodology: It was conducted an integrative review in the electronic databases PubMed, TripDataBase, Cochrane, Google Scholar and SciELO, science books (reference textbooks), convention documents, websites from public and private institutions and articles about the effects, clinical manifestations and treatment of human exposures to rodenticides. Documents were analyzed and the information organized into three themes: superwarfarin toxicity, clinical features and medical treatment, and non-anticoagulant rodenticides available in Chile. Results: In adults, the minimum dose reported to cause toxicity is 1 mg of active ingredient. In pediatric patients, accidental intakes rarely produce symptoms. The symptoms of poisoning are usually delayed and its toxicity is variable. The test of choice is International Normalized Ratio (INR) and it is performed in all patients with risk factors. The antidote must not be administered prophylactically and the dose is adjusted individually. Conclusions: Accidental intakes in children are not risky and they can be observed at home. Patients with massive intakes require INR monitoring for months so, it is important that an optimal coordination with primary care facilities still exists after medical discharge.

Possible unaware intoxication by anticoagulant rodenticide.

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.

Outcomes of patients with rodenticide poisoning at a far east poison center.

BACKGROUND: Rodenticide poisoning remains a major public health problem in Asian countries. Nevertheless, very few data are available in world literature regarding the outcomes of these patients. Therefore, the purpose of this study was to investigate the clinical outcomes of rodenticide poisonings in our hospital and to compare these data with published reports from other international poison centers. FINDINGS: We retrospectively examined the records of 20 patients with rodenticide poisoning (8 brodifacoum, 12 bromadiolone) who were referred to Chang Gung Memorial Hospital between 2000 and 2011. It was found that most of the rodenticide patients were middle-aged adults. Both genders were equally affected and many patients had a past history of major depressive disorder or schizophrenia. Nevertheless, patients with bromadiolone were referred significantly sooner than patients with brodifacoum poisoning (0.1 ± 0.1 versus 5.5 ± 10.5, P < 0.001). Furthermore, it was found that patients with brodifacoum suffered higher incidences of ecchymosis (50.0% versus 0%, P = 0.006) and hematuria (50.0% versus 0%, P = 0.006) than patients with bromadiolone poisoning. Laboratory analysis also demonstrated a poorer hemostatic profile of patients with brodifacoum [prothrombin time (PT), international normalized ratio (INR), 4.3 ± 4.8 versus 1.0 ± 0.1, P = 0.032; PT prolongation, 50.0% versus 0%, P = 0.006; activated partial thromboplastin time (aPTT) prolongation, 50.0% versus 0%, P = 0.006] than patients with bromadiolone poisoning. At the end of analysis, no patient died of the poisoning. CONCLUSION: The favorable outcome (zero mortality rate) is comparable to the published reports from other international poison centers. Further studies are warranted.

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.

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.