Anticoagulant Rodenticide Intoxication Research Articles

Treatment of a long-acting anticoagulant rodenticide poisoning cohort with vitamin K1 during the maintenance period.

Currently, there are few guidelines for the use of vitamin K1 in the maintenance treatment of long-acting anticoagulant rodenticide (LAAR) poisonings. We explored factors in the treatment of LAAR poisoning during the maintenance period in order to suggest feasible treatment models.Data from 24 cases of anticoagulant rodenticide poisoning in our hospital were collected from January 2013 to May 2016. The patients' sex, age, coagulation function, total time from poisoning to treatment with vitamin K1 (prehospital time), vitamin K1 sustained treatment time (VKSTT), anticoagulant rodenticide category, and specific poison dosage were collected. Multivariate analysis was used to evaluate the correlation between vitamin K1 dosage and other factors during the maintenance period.Only VKSTT (partial regression coefficient -1.133, 0.59, P = 0.035) had an obvious influence on the therapeutic dose of vitamin K1 required during the maintenance period.After an initial pulse therapy, the bleeding and coagulation functions were stabilized, and the patients were subsequently treated with vitamin K1 during the maintenance period. Over time, the maintenance dose of vitamin K1 (10-120 mg/d, intravenous drip) was gradually decreased and was not related to toxicant concentration.

Anticoagulant rodenticide intoxication in east China: a three-year analysis

ABSTRACTThe study was designed to analyze the incidence and pattern of anticoagulant rodenticide intoxication in east China and to discuss strategies of diagnosis based on laboratory analysis experience. A total of 117 patients with anticoagulant rodenticide poisoning confirmed by toxicological analysis in east China were included in this study from 2011 to 2013. The mean concentration of anticoagulant rodenticide, age, and gender of these patients, as well as the mode and type of poisoning, were discussed. The age ranged from less than 1 to 80 years with the feeble preponderance of males (M = 53.0%, F = 47.0%). The 0–9 age group covered the largest ratio of these anticoagulant rodenticide poisoning patients. Accidental or voluntary ingestion seems to be the most common cause of intoxication, with still the poisoning cause being unknown for a large number of positive analyses. Bromadiolone was the most commonly observed anticoagulant rodenticide found in the biological samples, followed by brodifacoum. The concentrations of bromadiolone and brodifacoum that were detected in the first collected whole blood from each patient ranged from 1 to 878 ng/mL (mean 97.9 ng/mL) and from 0.5 to 1566 ng/mL (mean 225.1 ng/mL), respectively. The data analysis shows a high incidence of anticoagulant rodenticide poisoning without awareness of the poisoned subjects, clearly emphasizing the need for toxicological analysis in patients with vitamin K-dependent coagulation disorder and restriction on availability of anticoagulant rodenticide.

Anticoagulant rodenticide toxicosis

While anticoagulant rodenticide ingestion is very common, especially in dogs, many animals do not develop signs. In symptomatic animals all clinical signs are related to coagulopathy, which can occur anywhere in the body. Internal bleeding is most common, particularly into the lungs. Initial signs may be non-specific with lethargy, weakness, anorexia, cough, depression and pale mucous membranes. Bleeding does not generally occur until 3–5 days after ingestion. The prothrombin time is the first test to become prolonged (but not until at least 36 hours post-ingestion) and the first to recover, so is used to monitor the need for antidotal therapy. Vitamin K1 is the specific antidote for anticoagulant rodenticide poisoning and it is required for at least 21 days because of the long half-life of these compounds. Prognosis depends on the severity and location of the bleeding.

Prothrombin Time Prolongation in Patients with Acute Intentional Anti-coagulant Rodenticide Intoxication

Prothrombin Time Prolongation in Patients with Acute Intentional Anti-coagulant Rodenticide Intoxication

Thromboelastographic Evaluation of Coagulation in a Dog with Anticoagulant Rodenticide Intoxication

Thromboelastographic Evaluation of Coagulation in a Dog with Anticoagulant Rodenticide Intoxication

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.

Causes of mortality and unintentional poisoning in predatory and scavenging birds in California

ObjectivesWe documented causes of mortality in an opportunistic sample of golden eagles, turkey vultures and common ravens, and assessed exposure to several contaminants that have been found in carrion and...

Assessment of a portable prothrombin time analyzer (CoaguChek-XS) in dogs.

To assess the performance of a portable prothrombin time (PT) analyzer (CoaguChek-XS) in dogs. Ninety-seven dogs composed of 20 healthy dogs, 45 ill dogs, and 32 ill dogs with altered coagulation. Samples were concurrently obtained and PT was measured using the CoaguChek-XS and an automated coagulation analyzer. Agreement between methods was assessed using Spearman's correlation and Bland-Altman analysis. The reference interval for PT using the CoaguChek-XS was 9.6-11.5 s. The CoaguChek-XS was easy to use, required a small volume of whole blood, and gave results within 1 min. The mean difference in PT between the 2 methods was 2.58 s (SD 3.10), and 94% of the samples fell within limits of agreement. The correlation was moderate, but significant (r = 0.35, P < 0.001). Sensitivity and specificity of the CoaguCheck-XS PT compared to analyzer PT were 92% and 56%, respectively, and increased to 95% and 77% on intent to treat basis. The coefficient of variance was 0.72%. The CoaguChek-XS identified all 8 dogs with anticoagulant rodenticide intoxication, although a discrepancy was noted from the analyzer results. In anemic dogs (PCV≤25%), the CoaguChek-XS did not display accurate results. The CoaguChek-XS is a simple, user-friendly, highly precise PT analyzer. Results had moderate correlation and good agreement with a standard method. It can be used reliably for screening dogs when the PT is normal. However, when the CoaguChek-XS PT is prolonged or when the PCV is ≤25%, results should be confirmed using a standard method.

Anticoagulant rodenticide screening in dogs: 123 cases (1996–2003)

To identify dogs with anticoagulant rodenticide (AR) screens submitted, determine whether detected concentrations of the anticoagulants correlated with severity of clinical signs for dogs with positive results on AR screens, and identify the most common disease processes present and the prognosis for those with negative AR screens. Retrospective case series. 123 dogs. History, signalment, clinical signs, physical examination findings, PCV, total solids concentration, prothrombin time, activated partial thromboplastin time, platelet count, AR concentrations, duration of hospitalization, blood products administered, final diagnosis, and outcome were recorded from medical records of dogs that underwent AR toxicology screenings. 75 of 123 (60.9%) dogs tested positive for AR. Dogs tested positive for brodifacoum, diphacinone (also called diphenadione), and chlorophacinone. Dogs with positive AR screenings weighed significantly less, received significantly more fresh frozen plasma, had significantly longer initial prothrombin time, and were significantly more likely to survive, compared with those with negative screens. Anticoagulant rodenticide concentrations ranged from trace amounts to 1,120 parts per billion and were not correlated with any recorded parameter. The most common conditions diagnosed in the 48 dogs with negative screens included neoplasia in 15 (31.3%), immune-mediated disease in 7 (14.6%), and gastrointestinal bleeding in 5 (10.4%) dogs. AR concentrations were not correlated with severity of clinical signs or the degree of prolongation of coagulation times in this series of patients. Patients with severe coagulopathies but negative results of AR screening had a poor prognosis, with neoplasia as the most common diagnosis. Anticoagulant rodenticide intoxication had the best prognosis, with a survival rate of 98.7% in this study.

Anticoagulant Rodenticides on our Public and Community Lands: Spatial Distribution of Exposure and Poisoning of a Rare Forest Carnivore

Anticoagulant rodenticide (AR) poisoning has emerged as a significant concern for conservation and management of non-target wildlife. The purpose for these toxicants is to suppress pest populations in agricultural or urban settings. The potential of direct and indirect exposures and illicit use of ARs on public and community forest lands have recently raised concern for fishers (Martes pennanti), a candidate for listing under the federal Endangered Species Act in the Pacific states. In an investigation of threats to fisher population persistence in the two isolated California populations, we investigate the magnitude of this previously undocumented threat to fishers, we tested 58 carcasses for the presence and quantification of ARs, conducted spatial analysis of exposed fishers in an effort to identify potential point sources of AR, and identified fishers that died directly due to AR poisoning. We found 46 of 58 (79%) fishers exposed to an AR with 96% of those individuals having been exposed to one or more second-generation AR compounds. No spatial clustering of AR exposure was detected and the spatial distribution of exposure suggests that AR contamination is widespread within the fisher’s range in California, which encompasses mostly public forest and park lands Additionally, we diagnosed four fisher deaths, including a lactating female, that were directly attributed to AR toxicosis and documented the first neonatal or milk transfer of an AR to an altricial fisher kit. These ARs, which some are acutely toxic, pose both a direct mortality or fitness risk to fishers, and a significant indirect risk to these isolated populations. Future research should be directed towards investigating risks to prey populations fishers are dependent on, exposure in other rare forest carnivores, and potential AR point sources such as illegal marijuana cultivation in the range of fishers on California public lands.

Primary and secondary poisoning by anticoagulant rodenticides of non-target animals in Spain

Anticoagulant rodenticide (AR) levels were studied in liver of 401 wild and domestic animals found dead in Spain with evidences of AR poisoning, including 2 species of reptiles (n=2), 42 species of birds (n=271) and 18 species of mammals (n=128). Baits (n=32) were also analyzed to detect the potential use of ARs in their intentional preparation to kill predators. AR residues were detected in 155 (38.7%) of the studied animals and 140 (34.9%) may have died by AR poisoning according to the clinical information, necropsy findings, residue levels and results of other toxicological analysis. Animals considered with sublethal AR exposure had total AR residues (geometric mean with 95% CI) in liver of 0.005 (0.003–0.007)μg/g wet weight (w.w.) and animals diagnosed as dead by AR poisoning had 0.706 (0.473–1.054)μg/g w.w. ARs were detected in 19% of baits illegally prepared to kill predators. In terms of the total incidents studied in our laboratory between 2005 and 2010 (n=1792 animals), confirmed poisonings represented 40.9% of the cases, and 21.1% of these were due to ARs (8.6% of the total sample). Nocturnal raptors (62%) and carnivorous mammals (38%) were amongst the secondary consumers with highest prevalence of AR exposure, especially to second generation ARs (SGARs). On the other hand, granivorous birds showed the highest prevalence of AR exposure (51%), especially to chlorophacinone in a region treated against a vole population peak in 2007. The presence of hemorrhages was significantly associated with AR levels in liver, but some animals (7.2%) with elevated residue levels (>0.2μg/g w.w.) showed no evidence of macroscopic bleeding. The use of accumulative SGARs and the application of baits on surface (i.e. treated grain by spreader machines) should be discontinued in future EU regulations on the use of rodenticides to prevent the poisoning of non-target wildlife species.

Toxicology and wildlife conservation in Europe: The inadequacy of current EU regulations

Anticoagulant rodenticide (AR) levels were studied in liver of 401 wild and domestic animals found dead in Spain with evidences of AR poisoning, including 2 species of reptiles (n = 2), 42 species of birds (n = 271) and 18 species of mammals (n = 128). Baits (n = 32) were also analyzed to detect the potential use of ARs in their intentional preparation to kill predators. AR residues were detected in 155 (38.7%) of the studied animals and 140 (34.9%) may have died by AR poisoning according to the clinical information, necropsy findings, residue levels and results of other toxicological analysis. Animals considered with sublethal AR exposure had total AR residues (geometric mean with 95% CI) in liver of 0.005 (0.003–0.007) μg/g wet weight (w.w.) and animals diagnosed as dead by AR poisoning had 0.706 (0.473–1.054) μg/g w.w. ARs were detected in 19% of baits illegally prepared to kill predators. In terms of the total incidents studied in our laboratory between 2005 and 2010 (n = 1792 animals), confirmed poisonings represented 40.9% of the cases, and 21.1% of these were due to ARs (8.6% of the total sample). Nocturnal raptors (62%) and carnivorous mammals (38%) were amongst the secondary consumers with highest prevalence of AR exposure, especially to second generation ARs (SGARs). On the other hand, granivorous birds showed the highest prevalence of AR exposure (51%), especially to chlorophacinone in a region treated against a vole population peak in 2007. The presence of hemorrhages was significantly associated with AR levels in liver, but some animals (7.2%) with elevated residue levels (> 0.2 μg/g w.w.) showed no evidence of macroscopic bleeding. The use of accumulative SGARs and the application of baits on surface (i.e. treated grain by spreader machines) should be discontinued in future EU regulations on the use of rodenticides to prevent the poisoning of non-target wildlife species.

Peliosis hepatis and hemoperitoneum in a dog with diphacinone intoxication

AbstractObjective: To describe the clinical course of a dog presented with peliosis hepatis and hemoperitoneum in concert with anticoagulant rodenticide intoxication.Case summary: A 7.75‐year‐old spayed female Shetland Sheepdog presented with clinical signs consistent with hypovolemia, hemoperitoneum, and a history of bright green stool 3 days before the onset of clinical signs. Initial packed cell volume/total solids were consistent with acute hemorrhage. A coagulation profile showed prolongation in activated clotting time and prolongation of both prothrombin and activated partial thromboplastin time, suggesting abnormal coagulation. Abdominal hemorrhage persisted in the face of normalization of the hemodynamic status and coagulation profile, and treatment with Vitamin K1. Abdominal ultrasound revealed multiple patchy hypoechoic areas throughout the caudate liver lobe. An exploratory laparotomy was performed 24 hours after presentation and revealed the caudate liver lobe as the source of the hemorrhage. Histopathologic examination of a specimen of the liver was consistent with peliosis hepatis. Toxicologic testing identified diphacinone levels in the blood consistent with anticoagulant rodenticide intoxication. Postoperative recovery was uneventful, and within 48 hours the dog was discharged. The dog returned to full function and a hepatic ultrasound performed 15 months postoperatively showed no significant abnormalities.New or unique information provided: Exposure to anticoagulant rodenticides may be associated with the development of peliosis hepatis in dogs.

Notoedric Mange in Two Free-ranging Mountain Lions (Puma concolor)

Two mountain lions (Puma con-color) were found dead in the Simi Hills area of southern California (Ventura County). Postmortem examination and toxicological analyses indicated that the cause of death was anticoagulant rodenticide intoxication. In addition, both lions had marked alopecia and skin crusts, caused by Notoedres cati. The diagnosis of notoedric mange was confirmed by histology and direct examination of mites obtained from skin scrapings of the two animals. Histologically, the affected skin showed acanthotic epidermis with parakeratosis and parasitic tunnels in the stratum corneum. This is the first report of the pathological changes associated with notoedric mange in free-ranging mountain lions.

A rodenticide exposed and bleeding Beagle dog with hereditary factor VII deficiency

AbstractObjective: To report a complex presentation of an acquired and hereditary coagulopathy in a dog.Case summary: A 5‐year‐old spayed female Beagle presented for lethargy, anorexia, cough, and stiff gait, and was diagnosed with a spontaneous hemothorax. The patient recovered from this bleeding episode suspected to be secondary to anticoagulant rodenticide intoxication, but was subsequently diagnosed with factor VII (FVII) deficiency, a hereditary coagulopathy. Diagnostic approach and management of FVII deficiency is described.New or unique information provided: This paper describes an unusual presentation of an inherited hemostatic disorder. Utilization of available screening and diagnostic tools, and appropriate interpretation of test results facilitate identification and management of this inherited coagulopathy.

Lethal paradoxical cerebral vein thrombosis due to suspicious anticoagulant rodenticide intoxication with chlorophacinone

Superwarfarin exposure is a growing health problem, described in many countries. The authors report a case of suspicious chlorophacinone poisoning with a problematic diagnosis. They review the literature and discuss particularities of anticoagulant rodenticide intoxication, as well as the apparent contradiction between anticoagulant intoxication and lethal thrombosis.

Haemorrhage in seven cats with suspected anticoagulant rodenticide intoxication

Clinical features were evaluated in seven adult cats (six males, one female) with haemorrhage and presumptive anticoagulant rodenticide intoxication. Haemorrhage appeared as thoracic haemorrhage, otic bleeding, haematoma, melena, haematochezia, and petechiation. The most common other presenting signs were lethargy, anorexia, and tachypnoea or dyspnoea. Six cats were anaemic, four cats were mildly thrombocytopenic (58 000–161 000/μl), and three had slightly decreased plasma protein or albumin values. The prothrombin time (30.3–>100 s, reference range: 16.5–27.5 s) and activated partial thromboplastin time values (32.6–>100 s; reference range: 14–25 s) were markedly prolonged in all cats. All cats received vitamin K 1subcutaneously or orally (3.7–5 mg/kg body weight initially) and depending on severity of signs five cats were transfused with fresh whole blood. Plasma coagulation times improved in all cats and returned to normal in 1–5 days. Rodenticide poisons represent an important but relatively rare cause of haemorrhage in cats and can be effectively treated.

Bilateral hydronephrosis secondary to anticoagulant rodenticide intoxication in a dog

AbstractObjective:To describe an unusual site of hemorrhage in a case of anticoagulant rodenticide toxicity.Case summary:A dog treated for Brodifacoum anticoagulant rodenticide intoxication was referred for treatment of thrombocytopenia and dysuria. Sonographic examination revealed a large blood clot within the urinary bladder, extending proximally along both ureters, and a bilateral hydronephrosis. In this dog, management of the vitamin K1‐dependent coagulopathy was unusually complicated by uremia and thrombocytopenia.New information provided:This is the first reported case of hydronephrosis secondary to anticoagulant rodenticide intoxication in a dog.

Bilateral hydronephrosis secondary to anticoagulant rodenticide intoxication in a dog

Bilateral hydronephrosis secondary to anticoagulant rodenticide intoxication in a dog

Thrombotest (PIVKA) Test Results in 25 Dogs with Acquired and Hereditary Caogulopathies

SummaryIn the veterinary literature, it has been suggested that a prolongation in the thrombotest (PIVKA test) is a sensitive and diagnostic indicator of anticoagulant rodenticide intoxication. We evaluated prothrombin time (PT), activated partial thromoplastin time (aPTT), and PIVKA indicator in 25 bleeding dogs: 7 with inherited coagulopathies. All dos with acquired coagulopathies had prolonged PIVKA values when compared to the normal controls. Factor VII deficient dogs had a prolonged PIVKA and PT test result, whereas dogs with intrinsic coagulopathies only had an aPTT prolongation. A three‐fold increase of the PIVKA or PT values was highly suggestive of an anticoagulant rodenticide poisoning compared to other acquired coagulopathies. Prolonged PIVKA resuls were not specific for anticoagulant rodenticide intoxication in our group of bleeding dogs.