bromfenacoum and Hemorrhage

Rodenticide (RD) application is the most effective chemical procedure against rodents. RDs containing indirect-action anticoagulants have received currently wide acceptance. When the recommended standards for handling these agents and precautionary measures in their use are violated, there may be poisoning, the main manifestation of which is hemorrhagic coagulation. The paper provides a literature review on poisoning by RDs having anticoagulant properties. This communication gives a detailed description of a clinical case of poisoning with brodifacoum contained in the ready-to-use Nutcracker bait due to long-term exposure to the rat poison that has a cumulative effect. Careful history data collection and coagulogram analysis make it possible to establish a correct clinical diagnosis and to use appropriate therapy that leads to patient recovery.

Topics: 4-Hydroxycoumarins; Adult; Animals; Anticoagulants; Blood Coagulation Disorders; Female; Hemorrhage; Humans; Male; Middle Aged; Rats; Rodenticides

We determine the incidence of clinically important bleeding in children with superwarfarin rodenticide ingestions not treated with gastrointestinal decontamination or prophylactic vitamin K.. We prospectively studied patients younger than 6 years of age who reported to our poison center with acute unintentional superwarfarin ingestions. Patients who received gastrointestinal decontamination or prophylactic vitamin K were excluded. Forty-eight- to 96-hour prothrombin time or international normalized ratio (INR) blood tests were recommended, and telephone contact was attempted at least 3 days after ingestion.. A total of 595 consecutive patients were enrolled during the 16-month study period. Fifty patients were excluded: 8 who were known to have ingested 1 pellet or less; 25 who received activated charcoal; 15 who were treated with induced emesis; and 2 who received prophylactic vitamin K. The resulting study group contained 545 patients. Eighty-two patients were lost to follow-up. Follow-up was obtained for 463 patients, including 222 by telephone contact alone, 62 by 48- to 96-hour INR, and 179 by both methods. None of the patients had clinically important coagulopathy. Two patients had an INR of 1.5 or greater (1.5 and 1.8) without symptoms. Single nosebleeds were reported in another 2 patients with normal 48-hour INRs. Another child had a small amount of blood crusted in the nose with no other symptoms and no laboratory work available. One child with a normal 48-hour INR had blood-streaked stools that were thought to be caused by an anal fissure.. Children with acute unintentional superwarfarin ingestions of less than 1 box may be managed without gastric decontamination or prophylactic vitamin K. Laboratory testing for coagulopathy should be reserved for cases involving clinically evident bleeding abnormalities.

Topics: 4-Hydroxycoumarins; Anticoagulants; Child; Child, Preschool; Decontamination; Female; Follow-Up Studies; Hemorrhage; Humans; International Normalized Ratio; Male; Poisoning; Prospective Studies; Prothrombin Time; Rodenticides; Treatment Outcome; Vitamin K

Bromadiolone, a widely-used rodent control drug, could act as a long-acting anticoagulant. Patients of bromadiolone poisoning often present with multiorgan hemorrhage. However, neurological symptoms of bromadiolone poisoning are seldom reported. We report a rare case with convulsive status epilepticus as the initial presentation of bromadiolone poisoning. A previously healthy 18-year-old man presented with persistent unconsciousness and repeated convulsive seizures. Magnetic resonance imaging revealed lesions in the corpus callosum. Laboratory test revealed the microscopic hematuria, prolonged prothrombin time, prolonged activated partial thromboplastin time and the presence of bromadiolone. The patient was diagnosed as the bromadiolone poisoning and treated with hemofiltration, vitamin K and prothrombin complex. Consciousness of the patient was regained and all neurological symptoms diminished after 7 days. Coagulopathy was totally corrected after 3 weeks, and a 2-month regimen of vitamin K supplementation was prescribed after discharge. Our case suggests that bromadiolone poisoning may involve the central nervous system. The atypical and initial symptoms of neurological disorders might lead to misdiagnosis of bromadiolone poisoning. Poisoning should be considered when acute neurological symptoms are combined with bleeding tendency. The vitamin K treatment is effective for both coagulopathy and central nervous system disorders in bromadiolone poisoning.

Topics: 4-Hydroxycoumarins; Anticoagulants; Hemorrhage; Humans; Rodenticides; Status Epilepticus

Synthetic cannabinoids contain many different chemicals and compounds, which pose new health risks to the population using these drugs. In May of 2018 the Center for Disease Control issued a health alert providing information on a multistate outbreak of coagulopathy from exposure to synthetic cannabinoid products containing a Vitamin K-dependent antagonistic agent such as brodifacoum. Recognizing signs, symptoms and imaging findings related to this outbreak is essential for clinicians caring for patients with a history or suspicion of using synthetic cannabinoids. To our knowledge, there are no studies that report the imaging findings demonstrating the coagulopathic complications associated with these synthetic compounds.

Topics: 4-Hydroxycoumarins; Blood Coagulation Disorders; Cannabinoids; Designer Drugs; Emergency Service, Hospital; Fatal Outcome; Hemorrhage; Humans; Male; Middle Aged; Tomography, X-Ray Computed; Vitamin K

A recent multi-state outbreak of life-threatening bleeding following inhalation of synthetic cannabinoids has been attributed to contamination with the long-acting anticoagulant rodenticide (LAAR) brodifacoum, a second-generation, highly potent, long-acting derivative of the commonly used blood thinner warfarin. While long-term treatment with high-dose vitamin K1 restores coagulation, it does not affect brodifacoum metabolism or clearance, and, consequently, brodifacoum remains in the human body for several months, thereby predisposing to risk of bleeding recurrence and development of coagulation-independent injury in extrahepatic tissues and fetuses. This has prompted the evaluation of pharmacological measures that accelerate brodifacoum clearance from poisoned patients. Since the induction of certain cytochrome P450 (CYP) enzymes accelerates warfarin metabolism, using CYP inducers, such as phenobarbital, to accelerate brodifacoum clearance seems plausible. However, unlike warfarin, brodifacoum does not undergo significant metabolism in the liver, nor have the effects of phenobarbital on vitamin K1 metabolism been previously determined. In addition, the safety of phenobarbital in brodifacoum-poisoned patients has not been established. Therefore, we propose that CYP inducers should not be used to accelerate the clearance of brodifacoum from poisoned patients, but that alternative approaches such as reducing enterohepatic recirculation of brodifacoum, or using lipid emulsions to scavenge brodifacoum throughout the body, be considered.

Topics: 4-Hydroxycoumarins; Anticoagulants; Blood Coagulation; Cytochrome P-450 Enzyme Inducers; Enterohepatic Circulation; Fat Emulsions, Intravenous; Half-Life; Hemorrhage; Humans; Inactivation, Metabolic; Vitamin K

A large-scale outbreak of life-threatening, inhaled synthetic cannabinoids (Spice/K2)-associated coagulopathy with bleeding complications was recently reported in Illinois. The causative agents were brodifacoum, difenacoum, and bromadiolone, potent, long-acting, 4-hydroxycoumarin anticoagulant rodenticides (LAAR) that were mixed with Spice/K2 products procured and then inhaled by the victims. We report on 3 poisoned patients who reside in underserved, socioeconomically disadvantaged neighborhoods of Chicago that were admitted and treated successfully at two inner-city, tertiary care hospitals in Chicago. The patients were discharged from the hospitals on daily long-term high-dose oral vitamin K

Topics: 4-Hydroxycoumarins; Administration, Inhalation; Adult; Aftercare; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation Disorders; Cannabinoids; Chicago; Female; Hemorrhage; Humans; International Normalized Ratio; Lost to Follow-Up; Male; Medication Adherence; Middle Aged; Patient Compliance; Synthetic Drugs; Vitamin K 1

More than 60 types of cannabinoids are found in nature; the remaining are chemically synthesized analogs of natural cannabinoids. Synthetic cannabinoids were first reported in the United States in 2008. These compounds are usually smoked by users and are sold under various names. Synthesized products have clinical effects that are similar to the effects of cannabis, which include tachycardia, conjunctival injection, nystagmus, vomiting, and ataxia. In cases of acute overdose, hyperthermia, acute kidney injury, seizures, and rhabdomyolysis can occur.. Deaths and life-threatening coagulopathies caused by brodifacoum (BDF) adulteration of synthetic cannabinoids have been reported in Illinois and other regions of the United States. BDF is a long-acting vitamin K-dependent antagonist that is often used as rat poison and that can cause massive hemorrhage. BDF is sometimes referred to as "superwarfarin" because the anticoagulant effect is 100 times greater than warfarin on a molar basis and its half-life is 20-130 days, which markedly exceeds that of warfarin. The rationale for lacing synthetic cannabinoids with BDF may be associated with attempts to enhance psychoactive effect of the drug, keeping the user high for a longer period of time because of lipid storage, hepatic metabolism, and slow release. We present the case of a healthy 27-year-old man who developed severe soft tissue hemorrhage and airway obstruction after use of a cannabinoid laced with BDF. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: To date there have been no case reports documenting severe soft tissue hemorrhage leading to airway obstruction and respiratory failure from synthetic cannabinoid use, whether or not the synthetic cannabinoid has been adulterated. Severe complications can arise from use, and treatment includes vitamin K and supportive therapy because the resulting coagulopathy can take days to weeks to resolve.

Topics: 4-Hydroxycoumarins; Adult; Airway Obstruction; Anticoagulants; Cannabinoids; Hemorrhage; Humans; Male; Soft Tissue Injuries; Vitamin K

A 7-y-old Weimaraner bitch was presented to emergency service after 3 h of active labor with no puppies produced. Hemoabdomen and hemothorax were present at the time of surgery; prothrombin time (PT) and activated partial thromboplastin time (aPTT) were both found to be within normal ranges. Surgical cesarean section was performed; 4 dead puppies and 5 live puppies were delivered. Because hemostasis was difficult to achieve, a hysterectomy was performed; however, the dog died as the operation was being completed. At autopsy, the pleural cavity contained 1.5 L of unclotted blood; the peritoneal cavity was relatively normal, and no obvious hemorrhage was associated with the surgical sites. All 4 dead fetuses were opened, and their pleural cavities were filled with unclotted blood. An anticoagulant screen was performed, and brodifacoum was identified in the liver of the bitch. This case is unusual in that the PT and aPTT were within reference intervals, but brodifacoum was present in sufficient amounts to potentially result in this dog bleeding to death, and also is suspected to have crossed the placenta and caused hemothorax and death in 4 of 9 puppies in utero.

Topics: 4-Hydroxycoumarins; Animals; Blood Coagulation Tests; Dogs; Fatal Outcome; Female; Fetus; Hemorrhage; Hemostasis; Humans; Partial Thromboplastin Time; Pregnancy; Rodenticides

Warfarin- and superwarfarin-type anticoagulants are commonly used as rodenticides. Exposure to these agents, especially superwarfarins with long-acting anticoagulant effect, can cause life-threatening coagulopathy in humans. Most superwarfarin poisoning cases had an obvious history of exposure, though occult cases without exposure history have also been reported. The current study aims to examine anticoagulant-type rodenticide poisoning in Hong Kong and to identify the similarities and differences between patients with known exposure history and those whose exposure is recognized only through laboratory testing.. The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. This was a retrospective cohort study of all patients with biochemically confirmed anticoagulant-type rodenticide exposure, from 2010 to 2014.. Superwarfarin was the most common group of anticoagulant-type rodenticides identified (87.8%), in which bromadiolone and brodifacoum were the most frequently encountered. Among the 41 cases identified, 31 had an obvious exposure history, and 10 were occult poisoning in which the context of exposure remained unidentified. All occult poisoning patients without exposure history presented with bleeding events. These occult poisoning cases often went unrecognized by frontline clinicians, leading to delayed investigation and initiation of treatment. This group of patients was associated with a longer time to diagnose coagulopathy (p < 0.001) and confirm rodenticide poisoning (p < 0.05), a higher rate of international normalized ratio (INR) rebound after initiation of antidote (p < 0.001), and a longer time needed for normalizing INR (p < 0.05).. Occult superwarfarin poisoning is an important yet under-recognized differential cause of unexplained coagulopathy. A high index of clinical suspicion and availability of specialized toxicological test for superwarfarins play a vital role in diagnosis and early initiation of appropriate management. The underlying cause of such poisoning remains obscure and warrants further study.

Topics: 4-Hydroxycoumarins; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Blood Coagulation Disorders; Cohort Studies; Female; Hemorrhage; Hong Kong; Humans; Infant; International Normalized Ratio; Male; Middle Aged; Poisoning; Retrospective Studies; Rodenticides; Vitamin K; Warfarin; Young Adult

Patients exposed to long acting anticoagulant rodenticides (LAARs) are typically administered large amounts of oral vitamin K1 (VK1) to counteract life-threatening anticoagulant effects. Although VK1 treatment effectively prevents mortality, additional methods are needed to reduce the long duration of VK1 treatment which can last for months at high expense. We developed a model of brodifacoum (BDF) poisoning, one of the most potent LAARs, in adult male New Zealand White (NZW) rabbits. The LD50 for oral BDF was determined to be 192 μg/kg, similar to that calculated for adult rats. However, in contrast to rats, NZW rabbits exhibited severe internal hemorrhage including in the brain, symptoms which mimic what occurs in cases of human poisoning. Similar to warfarin, BDF and other LAARs undergo enterohepatic recirculation which contributes to their long half-lives. We therefore tested effects of cholestyramine (CSA), an FDA-approved bile sequestrant, on BDF-induced mortality. When given daily (0.67 g/kg, oral) starting the day of BDF administration, CSA reduced mortality from 67% to 11%. At the same CSA prevented the increase in clotting time, and reduced the decrease in core body temperature due to BDF. Given its excellent safety record and that it is approved for children older than 6 years, these findings suggest CSA could be considered as an adjunct to VK1 for treatment of LAAR poisoning.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Bile Acids and Salts; Cholestyramine Resin; Hemorrhage; Lethal Dose 50; Male; Rabbits; Rodenticides; Survival Analysis; Vitamin K 1

Acute, unintentional drug-related poisonings lead to an estimated 418,313 ED visits in 2014, according to the latest statistics from the Center for Disease Control and Prevention. While most of these were opiate-related poisonings, anticoagulant rodenticides were the most common cause of rodenticide-related poisoning in the United States. Many clinical syndromes and treatment algorithms have been described for patients with anticoagulant rodenticide poisoning. We report a case of an acute ingestion of two anticoagulant rodenticides and successful reversal of coagulation parameters using 4-factor prothrombin complex concentrate in a fixed-dose approach.

Topics: 4-Hydroxycoumarins; Abdominal Pain; Aged; Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Drug Contamination; Drug Dosage Calculations; Hemorrhage; Humans; Illicit Drugs; Male; Rodenticides; Synthetic Drugs; Treatment Outcome; Vitamin K

In March and April 2018, more than 150 patients presented to hospitals in Illinois with coagulopathy and bleeding diathesis. Area physicians and public health organizations identified an association between coagulopathy and synthetic cannabinoid use. Preliminary tests of patient serum samples and drug samples revealed that brodifacoum, an anticoagulant, was the likely adulterant.. We reviewed physician-reported data from patients admitted to Saint Francis Medical Center in Peoria, Illinois, between March 28 and April 21, 2018, and included in a case series adult patients who met the criteria used to diagnose synthetic cannabinoid-associated coagulopathy. A confirmatory anticoagulant poisoning panel was ordered at the discretion of the treating physician.. A total of 34 patients were identified as having synthetic cannabinoid-associated coagulopathy during 45 hospitalizations. Confirmatory anticoagulant testing was performed in 15 of the 34 patients, and superwarfarin poisoning was confirmed in the 15 patients tested. Anticoagulant tests were positive for brodifacoum in 15 patients (100%), difenacoum in 5 (33%), bromadiolone in 2 (13%), and warfarin in 1 (7%). Common symptoms at presentation included gross hematuria in 19 patients (56%) and abdominal pain in 16 (47%). Computed tomography was performed to evaluate abdominal pain and revealed renal abnormalities in 12 patients. Vitamin K. Our data indicate that superwarfarin adulterants of synthetic cannabinoids can lead to clinically significant coagulopathy. In our series, in most of the cases in which the patient presented with bleeding diathesis, symptoms were controlled with the use of vitamin K

Topics: 4-Hydroxycoumarins; Abdominal Pain; Adult; Anticoagulants; Blood Coagulation Disorders; Blood Transfusion; Cannabinoids; Female; Hematuria; Hemorrhage; Humans; Illinois; International Normalized Ratio; Male; Middle Aged; Patient Readmission; Vitamin K; Warfarin

Five horses originating from 4 different California race tracks were submitted to the California Animal Health and Food Safety Laboratory for necropsy and diagnostic workup. The 5 horses had a history of sudden collapse and death during exercise. In all of them, massive hemoperitoneum and hemorrhages in other cavities or organs were observed. The liver from these 5 animals and from 27 horses that had been euthanized due to catastrophic leg injuries (controls) were subjected to a rodenticide anticoagulant screen. Traces of brodifacoum, diphacinone, or bromadiolone were detected in the 5 horses with massive bleeding (5/5), and no traces of rodenticides were detected in control horses (0/27). Other frequent causes of massive hemorrhages in horses were ruled out in 4 of the cases; one of the horses had a pelvic fracture. Although only traces of anticoagulants were found in the livers of these horses and the role of these substances in the massive bleeding remains uncertain, it is speculated that exercise-related increases in blood pressure may have reduced the threshold for toxicity of these anticoagulants.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; California; Hemoperitoneum; Hemorrhage; Horse Diseases; Horses; Liver; Male; Phenindione; Physical Conditioning, Animal; Rodenticides

Based on detection of hepatic residues, scavenging and predatory non-target raptors are widely exposed to second generation anticoagulant rodenticides (SGARs). A small proportion, generally <10%, of tested birds are diagnosed as acutely poisoned. Little is known, however, of sub-lethal effects of SGARs, such as interaction of clotting capacity with traumatic injury. Assessment of coagulation function of birds submitted live to wildlife rehabilitators or veterinarians may provide a means of establishing the proportion of animals suffering sub-lethal coagulopathies, as well as identifying individuals requiring treatment. As a first step in exploring the potential of this approach, we dosed Japanese quail (Coturnix japonica) with the SGAR, brodifacoum, at 0, 0.8, 1.4, 1.9, and 2.5 mg/kg and sampled birds at 1, 3, 5 and 7 days post-dosing. Prothrombin time (PT), which measures the extrinsic coagulation pathway, was significantly prolonged in 98% of brodifacoum-exposed quail in a dose- and time-dependent manner. 50-fold prolongation of PT occurred at higher brodifacoum dosages and correlated to hemorrhage found at necropsy. Activated clotting time (ACT), a measure of the intrinsic pathway also increased with dose and time. Hemoglobin (Hb) and hematocrit (Hct) decreased dose- and time-dependently at doses ≥1.4 mg/kg with no significant change at 0.8 mg/kg. Reference intervals for PT (10.0-16.2 s), ACT (30-180 s), Hb (9.6-18.4 g/dl), and Hct (34-55%) were established in Japanese quail. Species-specific reference intervals are required as barn owl PT (17-29 s) and quail PT were different. The proportion of brodifacoum-exposed quail with hemorrhage was not correlated with liver residues, but was correlated with PT, suggesting that this assay is a useful indicator of avian anticoagulant rodenticide exposure. PTs measured in free-living barn owls sampled between April 2009 and August 2010 in the lower Fraser Valley of BC do not suggest significant exposure to SGARs.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Blood Coagulation; Coturnix; Dose-Response Relationship, Drug; Hemorrhage; Liver; Prothrombin Time; Rodenticides; Strigiformes; Time Factors

Brodifacoum poisoning occurs as a result of ingestion of rodenticide compounds. It acts as a superwarfarin, inhibiting vitamin K epoxide reductase, in an irreversible fashion much like warfarin but with a much longer half-life. A 48-year-old female patient reported 4 days of mild dyspnea, dry cough, bilateral popliteal fossae pain and diffuse upper abdominal pain. She had no history of liver disease or alcohol or illicit substance abuse. Initial physical examination was remarkable only for mildly pale conjunctivae and mild abdominal tenderness and pain in the left popliteal fossa. A complete blood count and complete metabolic panel were normal. Prothrombin time (PT) was above 100 s, partial thromboplastin time (PTT) was above 200 s and international normalized ratio was reported as above 12.0. Urinalysis revealed hematuria. Venous Doppler ultrasound of lower extremities demonstrated left popliteal vein thrombosis. Computed tomography scan of the abdomen demonstrated transmural hematoma, and fecal occult blood test was positive. A full anticoagulant work-up showed critical reduction of vitamin K-dependent factors II, VII, IX and X. PT and PTT corrected with mixing studies proving factor deficiency as the cause of the coagulopathy. Lupus anticoagulant studies were negative. Superwarfarin toxicity was suspected and confirmed with an anticoagulant poison panel positive for brodifacoum. The patient was hospitalized and successfully treated with fresh frozen plasma, cryoprecipitate and vitamin K. In conclusion, paradoxical thrombosis and hemorrhage should raise the suspicion for superwarfarin toxicity in the appropriate clinical setting. Further studies are required to define the management of these patients.

Topics: 4-Hydroxycoumarins; Female; Hemorrhage; Humans; Middle Aged; Rodenticides; Thrombosis

Topics: 4-Hydroxycoumarins; Adolescent; Adult; Aged; Anticoagulants; Causality; Child; Child, Preschool; China; Disease Outbreaks; Female; Hemorrhage; Humans; Male; Middle Aged; Rodenticides

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.

Topics: 4-Hydroxycoumarins; Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Environmental Exposure; Female; Hemorrhage; Humans; Male; Middle Aged; Partial Thromboplastin Time; Prothrombin Time; Republic of Korea; Treatment Outcome; Vitamin K 1

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Hemorrhage; Humans; Male; Venous Thrombosis; Young Adult

Fatal brodifacoum poisoning in a pony is described; this condition has not previously been reported in ponies. Discussion of what factors in the pony's history and treatment may have predisposed to the severity and ultimate death is provided.

Topics: 4-Hydroxycoumarins; Animals; Anticoagulants; Fatal Outcome; Female; Hemorrhage; Horse Diseases; Horses; Rodenticides

Superwarfarins are widely used as rodenticides. They are similar to warfarin, but they are more potent and act longer. In case of poisoning, they cause severe bleeding, usually from multiple sites.. A 67-yr-old man was admitted with melaena, epistaxis and haemarthrosis in his left knee. PT, INR and aPTT were markedly increased. Initially, the patient was treated with blood and fresh frozen plasma (FFP) transfusions. However at the second day, PT, INR and aPTT were even worse. The combination of persistent coagulopathy, normal mixing studies, normal liver function tests and absence of hepatic failure or malabsorption syndromes lead to the suspicion of vitK dependent clotting factors deficiency due to superwarfarin poisoning. Indeed, the patient admitted a suicide attempt with rodenticide, although he had previously denied it. Psychiatric evaluation revealed a disturbed personality. Melaena stopped after 7 d. Then, the patient was administered 30 mg of vitK daily for a total period of 4 months.. Superwarfarin poisoning leads to severe bleeding, usually from multiple sites. Prolonged treatment with high doses of vitK is necessary. Haemarthrosis, as a complication of superwarfarin poisoning, is presented here for the first time in literature.

Topics: 4-Hydroxycoumarins; Aged; Blood Coagulation Tests; Hemarthrosis; Hemorrhage; Humans; Male; Rodenticides; Vitamin K; Vitamin K Deficiency

The authors present the case of a 44-year-old American Indian woman with hematemesis, spontaneous cutaneous hemorrhages, and multiple ecchymoses. Coagulation factor analyses demonstrated both prolonged prothrombin time (PT, >40 s) and prolonged partial thromboplastin time (PTT, >120 s). Measurement of the serum level of brodifacoum (37 ng/mL), one of the superwarfarin agents commonly used in rodenticides, confirmed poisoning as the cause of the patient's symptoms. Substantial amounts of fresh frozen plasma and vitamin K were required to obtain normal coagulation parameters and maintain these parameters over a 3-week inhospital period. Oral administration of vitamin K (100 mg daily) maintained normal PT (14.1 s), PTT (33.0 s), and international normalized ratio (INR, 1.48) at 2 weeks after the patient was discharged from the hospital. By 2 months postdischarge, PT, PTT, and INR returned to elevated levels because of patient noncompliance with the prescribed tapering vitamin K regimen.

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Female; Hematemesis; Hemorrhage; Humans; Poisoning; Skin Diseases

The use of second-generation anticoagulants termed "superwarfarins" as rodenticides, although widespread, is poorly controlled. Products containing superwarfarin have been marketed in over-the-counter rodenticides and can be easily purchased. Poor control potentiates the risk of accidental or intentional poisoning, but clinicians may underestimate the incidence of superwarfarin toxicity. Therefore, when cases of unexplained acquired coagulopathy and selective deficiency of vitamin K-dependent clotting factors occur in patients in the absence of liver disease or inhibitors, physicians should consider the possibility of superwarfarin poisoning as a cause. According to our own experience, recombinant activated factor VII (NovoSeven; Novo Nordisk, Bagsvaerd, Denmark) appears to be a safe and effective therapy for acute bleeding caused by superwarfarin poisoning. Due to the extended half-life of the second-generation rodenticides, follow-up therapy with oral vitamin K1 should be of long-term duration.

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Blood Coagulation Tests; Diagnosis, Differential; Drug Overdose; Factor VII; Factor VIIa; Female; Hemorrhage; Humans; Male; Recombinant Proteins; Rodenticides

Eight out of a litter of 13 puppies were either born dead or died within 48 hours of birth. Three puppies that died shortly after birth were necropsied. Two puppies had hemorrhage in the thoracic and peritoneal cavities, intestinal serosa, and meninges. The third puppy was smaller than the other two puppies but did not have detectable hemorrhage. Brodifacoum, a second-generation coumarin anticoagulant, was detected in livers from the two puppies with hemorrhage. The dam did not have clinical signs of coagulopathy before or subsequent to whelping. The owners were confident that the dog had not been exposed to rodenticide for at least 4 weeks before whelping. A presumptive diagnosis of in utero brodifacoum toxicity was made. To the authors' knowledge this is the first time a second-generation coumarin anticoagulant has been detected in the liver of a newborn animal. This case is also unique because the dam was unaffected, suggesting that fetuses are more susceptible to brodifacoum toxicity than adult animals.

Topics: 4-Hydroxycoumarins; Animals; Animals, Newborn; Anticoagulants; Dog Diseases; Dogs; Female; Fetus; Hemorrhage; Liver; Maternal-Fetal Exchange; Pregnancy

Topics: 4-Hydroxycoumarins; Adult; Blood Coagulation Disorders; Blood Coagulation Factors; Crack Cocaine; Drug Synergism; Epistaxis; Hemorrhage; Humans; Male; Retroperitoneal Space; Rodenticides

Physicians must have a high index of suspicion when patients have unexplained prolongation of the prothrombin time and bleeding in the absence of detectable warfarin. Several common rodenticides contain modified versions of warfarin that are not detectable in standard warfarin assays. We present a case of surreptitious brodifacoum ingestion in a patient who had years of unexplained bleeding and negative warfarin levels.

Topics: 4-Hydroxycoumarins; Anticoagulants; Factitious Disorders; Female; Hemorrhage; Humans; Middle Aged; Poisoning; Rodenticides

Ingestion of long-acting anticoagulant rodenticides such as brodifacoum can lead to prolonged and life-threatening coagulopathy. A paucity of conflicting information is available on brodifacoum's half-life and elimination pharmacokinetics. In addition, the optimal dose, duration, and route of administration of vitamin K(1) therapy are unknown. We report the case of a 52-year-old man who ingested eight 43-g boxes of a rodenticide (d-Con Mouse-Prufe II; 0.005% brodifacoum; Reckitt & Colman, Wayne, NJ). This case demonstrates that after stabilization with fresh frozen plasma, high-dose oral vitamin K(1) therapy ( congruent with 7 mg/kg per 24 hours divided every 6 hours) was effective in treating brodifacoum-induced coagulopathy. The concentration of vitamin K(1) required for normal coagulation in this case was less than the accepted value of 1 microg/mL, which is derived from a rabbit model. In this case, brodifacoum appears to follow zero-order elimination pharmacokinetics. In future cases of patients with ingestions of long-acting anticoagulants who present with coagulopathy, it may be useful to obtain serial brodifacoum concentrations to determine elimination curves to help predict the duration of oral vitamin K(1) therapy.

Topics: 4-Hydroxycoumarins; Administration, Oral; Drug Overdose; Follow-Up Studies; Half-Life; Hemorrhage; Humans; Male; Metabolic Clearance Rate; Middle Aged; Plasma; Rodenticides; Suicide, Attempted; Vitamin K

From 1971 through 1997, we documented 51 cases (55 individual animals) of poisoning of non-target wildlife in New York (plus two cases in adjoining states) (USA) with anticoagulant rodenticides--all but two of these cases occurred in the last 8 yrs. Brodifacoum was implicated in 80% of the incidents. Diphacinone was identified in four cases, bromadiolone in three cases (once in combination with brodifacoum), and chlorophacinone and coumatetralyl were detected once each in the company of brodifacoum. Warfarin accounted for the three cases documented prior to 1989, and one case involving a bald eagle (Haliaeetus leucocephalus) in 1995. Secondary intoxication of raptors, principally great horned owls (Bubo virginianus) and red-tailed hawks (Buteo jamaicensis), comprised one-half of the cases. Gray squirrels (Sciurus carolinensis), raccoons (Procyon lotor) and white-tailed deer (Odocoileus virginianus) were the most frequently poisoned mammals. All of the deer originated from a rather unique situation on a barrier island off southern Long Island (New York). Restrictions on the use of brodifacoum appear warranted.

Topics: 4-Hydroxycoumarins; Animals; Animals, Wild; Anticoagulants; Bird Diseases; Deer; Hemorrhage; Indans; New York; Phenindione; Poisoning; Raccoons; Raptors; Rodenticides; Sciuridae; Warfarin

This report details the pathologic and toxicologic findings in the case of a 15-year-old girl who deliberately and fatally ingested brodifacoum, a commonly used rodenticide. The mechanism of death, massive pulmonary hemorrhage, has not been previously reported. Brodifacoum was quantitated in liver, spleen, lung, brain, bile, vitreous humor, heart blood, and femoral blood using HPLC with fluorescence detection. The highest brodifacoum concentrations were detected in bile (4276 ng/mL) and femoral blood (3919 ng/mL). No brodifacoum was detected in brain or vitreous humor. A brodifacoum concentration of 50 ng/g was observed in frozen liver while formalin fixed liver exhibited a concentration of 820 ng/g. A very high blood:liver brodifacoum concentration ratio suggested acute poisoning but the historical and pathologic findings suggested a longer period of anticoagulation. Though most cases of brodifacoum poisoning in humans are non-fatal, this compound can be deadly because of its very long half-life. Forensic pathologists and toxicologists should suspect superwarfarin rodenticides when confronted with cases of unexplained bleeding. Anticoagulant poisoning can mimic fatal leukemia or infectious diseases such as bacterial sepsis, rickettsioses, plague, and leptospirosis. A thorough death scene investigation may provide clues that a person has ingested these substances.

Topics: 4-Hydroxycoumarins; Adolescent; Chromatography, High Pressure Liquid; Female; Hemorrhage; Humans; Lung Diseases; Pulmonary Alveoli; Rodenticides; Suicide; Tissue Distribution

A case of self-ingestion of brodifacoum that resulted in spontaneous intra-abdominal haemorrhage, circulatory shock, rhabdomyolysis and acute renal failure is reported. Current knowledge and management of superwarfarin poisoning are discussed.

Topics: 4-Hydroxycoumarins; Adult; Anticoagulants; Hemorrhage; Humans; Male; Renal Insufficiency; Rhabdomyolysis; Rodenticides; Shock; Suicide, Attempted

A 36-month-old child had spontaneous hemorrhage from her nose, mouth, and urinary tract, and a fall in hemoglobin of 20 gm/L (2 gm/dl). The prothrombin time and partial thromboplastin time were markedly prolonged with a decrease in the vitamin K-dependent factors. The child had ingested brodifacoum, a long-acting rodenticide. Prolonged follow-up and treatment with vitamin K were necessary.

Topics: 4-Hydroxycoumarins; Child, Preschool; Female; Hemorrhage; Humans; Poisoning; Rodenticides; Vitamin K

A 27-year-old woman with severe vitamin K deficiency presented with hemoptysis and diffuse pulmonary infiltrates. She rapidly developed respiratory failure requiring ventilatory support. Surreptitious ingestion of brodifacoum, a long-acting warfarin derivative, was ultimately found to be the cause of her coagulopathy and DAH.

Topics: 4-Hydroxycoumarins; Adult; Factitious Disorders; Female; Hemorrhage; Humans; Lung Diseases; Poisoning; Rodenticides

The "superwarfarin" compounds are 4-hydroxy derivatives of coumarin that have increased activity and a longer duration of action than the parent compound. The superwarfarins are used widely in the United States as rodenticides and are effective against warfarin-resistant strains of rats. A chronic accidental ingestion of one of these products, brodifacoum, by a 7-year-old child who had bleeding and laboratory evidence suggestive of a vitamin K-related coagulopathy is reported. The bleeding manifestations were severe and prolonged, requiring 13 months for normalization of coagulation times. With a negative history of ingestion and despite clinical suspicion, documentation of superwarfarin poisoning was hampered by the lack of readily available assays for these compounds, even from the manufacturers. Brodifacoum was also identified in rat feces from the family home. This finding raises the concern of poisoning not only from ingestion of brodifacoum particles themselves, but also from a fecal-oral route. A review of the literature is presented and the implications of this case for the practicing physician are discussed.

Topics: 4-Hydroxycoumarins; Child; Female; Hemorrhage; Humans; Poisoning; Rodenticides

Topics: 4-Hydroxycoumarins; Animals; Chromatography, Thin Layer; Dog Diseases; Dogs; Hemorrhage; Rodenticides