Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine.

PubMed

Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

2017-01-02

Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1 H nuclear magnetic resonance ( 1 H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity and the feeding indexes of R 1 and R 2 were tested. The result of the experiment proved that the new synthesis of 1, 3 - indan diketone for maternal new anticoagulant rodenticide can replace the current 4 - hydroxyl coumarin as the mother of the second generation anticoagulant rodenticide and 1, 3 - indan diketone for maternal new anticoagulant rodenticides will have a good development prospect.

A comparative assessment of efficacy of three anticoagulant rodenticides.

PubMed

Renapurkar, D M

1982-01-01

Results are presented of feeding tests carried out with three common anticoagulant rodenticides viz., coumatetralyl, fumarin and warfarin on three common species of commensal rodents i.e., Rattus rattus, Rattus norvegicus and Bandicota bengalensis. All three species of rodents were susceptible to anticoagulant rodenticides. However, the action of these compounds in B. bengalensis was comparatively slow. Coumatetralyl was found to be the most effective rodenticide followed by fumarin and warfarin. Liquid baits of these compounds are more effective in comparison to food baits.

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

PubMed Central

Kelly, Terra R.; Poppenga, Robert H.; Woods, Leslie A.; Hernandez, Yvette Z.; Boyce, Walter M.; Samaniego, Francisco J.; Torres, Steve G.; Johnson, Christine K.

2014-01-01

Objectives We 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 common prey for these species. Methods Dead birds were submitted for testing through wildlife rehabilitation centres and a network of wildlife biologists in California from 2007 to 2009. Results The leading causes of mortality in this study were collision-related trauma (63 per cent), lead intoxication (17 per cent) and anticoagulant rodenticide poisoning (8 per cent). Elevated liver lead concentration (≥2 µg/g) and bone lead concentration (>6 µg/g) were detected in 25 and 49 per cent of birds tested, respectively. Approximately 84 per cent of birds tested had detectable rodenticide residues. The majority of rodenticide exposure occurred in peri-urban areas, suggesting that retail sale and use of commensal rodent baits, particularly in residential and semi-residential areas in California, may provide a pathway of exposure. Conclusions Monitoring anthropogenic causes of mortality in predatory and scavenging bird species provides important data needed to inform on mitigation and regulatory efforts aimed at reducing threats to these populations. PMID:26392875

Anticoagulant rodenticide toxicity to non-target wildlife under controlled exposure conditions

USGS Publications Warehouse

Rattner, Barnett A.; Mastrota, F. Nicholas; van den Brink, Nico; Elliott, J.; Shore, R.; Rattner, B.

2018-01-01

Much of our understanding of anticoagulant rodenticide toxicity to non-target wildlife has been derived from molecular through whole animal research and registration studies in domesticated birds and mammals, and to a lesser degree from trials with captive wildlife. Using these data, an adverse outcome pathway identifying molecular initiating and anchoring events (inhibition of vitamin K epoxide reductase, failure to activate clotting factors), and established and plausible linkages (coagulopathy, hemorrhage, anemia, reduced fitness) associated with toxicity, is presented. Controlled exposure studies have demonstrated that second-generation anticoagulant rodenticides (e.g., brodifacoum) are more toxic than first- and intermediate-generation compounds (e.g., warfarin, diphacinone), however the difference in potency is diminished when first- and intermediate-generation compounds are administered on multiple days. Differences in species sensitivity are inconsistent among compounds. Numerous studies have compared mortality rate of predators fed prey or tissue containing anticoagulant rodenticides. In secondary exposure studies in birds, brodifacoum appears to pose the greatest risk, with bromadiolone, difenacoum, flocoumafen and difethialone being less hazardous than brodifacoum, and warfarin, coumatetralyl, coumafuryl, chlorophacinone and diphacinone being even less hazardous. In contrast, substantial mortality was noted in secondary exposure studies in mammals ingesting prey or tissue diets containing either second- or intermediate-generation compounds. Sublethal responses (e.g., prolonged clotting time, reduced hematocrit and anemia) have been used to study the sequelae of anticoagulant intoxication, and to some degree in the establishment of toxicity thresholds or toxicity reference values. Surprisingly few studies have undertaken histopathological evaluations to identify cellular lesions and hemorrhage associated with anticoagulant rodenticide exposure in non-target wildlife. Ecological risk assessments of anticoagulant rodenticides would be improved with additional data on (i) interspecific differences in sensitivity, particularly for understudied taxa, (ii) sublethal effects unrelated to coagulopathy, (iii) responses to mixtures and sequential exposures, and (iv) the role of vitamin K status on toxicity, and significance of inclusion of supplemental vitamin K or menadione (provitamin) in the diet of test organisms. A more complete understanding of the toxicity of anticoagulant rodenticides in non-target wildlife would enable regulators and natural resource managers to better predict and even mitigate risk.

Use of anticoagulant rodenticides by pest management professionals in Massachusetts, USA.

PubMed

Memmott, Kristin; Murray, Maureen; Rutberg, Allen

2017-01-01

Secondary exposure to chemical rodenticides, specifically second-generation anticoagulant rodenticides (SGARs), poses a threat to non-target wildlife including birds of prey. Federal regulations in the United States currently limit homeowner access to SGARs as a way of minimizing this threat. With legal access to SGARs, pest management professionals (PMPs) represent a potential linkage to non-target exposure. There is limited research focused on rodent control practices, chemical rodenticide preferences, level of concern and awareness, or opinions on rodenticide regulations as they relate to PMPs. An online survey was sent to PMP companies across Massachusetts, USA, between October and November 2015. Thirty-five responses were obtained, a 20 % response rate. The preferred rodent control method among responding PMP companies was chemical rodenticides, specifically the SGAR bromadiolone. Respondents varied in their level of concern regarding the impact of chemical rodenticides on non-target species and showed a low level of awareness regarding SGAR potency and half-life. All responding companies reported using integrated pest management (IPM) strategies, with nearly all utilizing chemical rodenticides at some point. Enhanced education focused on SGAR potency, bioaccumulation potential, exposure routes, and negative impacts on non-target wildlife may improve efforts made by PMPs to minimize risk to wildlife and decrease dependence on chemical rodenticide use. Future studies evaluating use of anticoagulant rodenticide (ARs) by PMPs and the association with AR residues found in non-target wildlife is necessary to determine if current EPA regulations need to be modified to effectively reduce the risk of SGARs to non-target wildlife.

Grass is not always greener: Rodenticide exposure of a threatened species near marijuana growing operations

USGS Publications Warehouse

Franklin, Alan B.; Carlson, Peter C.; Rex, Angela; Rockweit, Jeremy T.; Garza, David; Culhane, Emily; Volker, Steven F; Dusek, Robert J.; Shearn-Bochsler, Valerie I.; Gabriel, Mourad W.; Horak, Katherine E.

2018-01-01

ObjectiveMarijuana (Cannabis spp.) growing operations (MGO) in California have increased substantially since the mid-1990s. One environmental side-effect of MGOs is the extensive use of anticoagulant rodenticides (AR) to prevent damage to marijuana plants caused by wild rodents. In association with a long-term demographic study, we report on an observation of brodifacoum AR exposure in a threatened species, the northern spotted owl (Strix occidentalis caurina), found freshly dead within 669–1347 m of at least seven active MGOs.ResultsLiver and blood samples from the dead northern spotted owl were tested for 12 rodenticides. Brodifacoum was the only rodenticide detected in the liver (33.3–36.3 ng/g) and blood (0.48–0.54 ng/ml). Based on necropsy results, it was unclear what role brodifacoum had in the death of this bird. However, fatal AR poisoning has been previously reported in owls with relatively low levels of brodifacoum residues in the liver. One likely mechanism of AR transmission from MGOs to northern spotted owls in California is through ingestion of AR contaminated prey that frequent MGOs. The proliferation of MGOs with their use of ARs in forested landscapes used by northern spotted owls may pose an additional stressor for this threatened species.

Suspected poisoning of domestic animals by pesticides.

PubMed

Caloni, Francesca; Cortinovis, Cristina; Rivolta, Marina; Davanzo, Franca

2016-01-01

A retrospective study was carried out by reviewing all suspected cases of domestic animal poisoning attributed to pesticides, reported to the Milan Poison Control Centre (MPCC) between January 2011 and December 2013. During this period, pesticides were found to be responsible for 37.3% of all suspected poisoning enquiries received (815). The most commonly species involved was the dog (71.1% of calls) followed by the cat (15.8%), while a limited number of cases involved horses, goats and sheep. Most cases of exposure (47.1%) resulted in mild to moderate clinical signs. The outcome was reported in 59.9% of these cases, with death occurring in 10.4% of them. Insecticides (40.8%) proved to be the most common group of pesticides involved and exposure to pyrethrins-pyrethroids accounted for the majority of calls. According to the MPCC data, there has been a decrease in the number of suspected poisonings cases attributed to pesticides that have been banned by the EU, including aldicarb, carbofuran, endosulfan and paraquat. In contrast, there has been an increase of suspected poisoning cases attributed to the neonicotinoids, imidacloprid and acetamiprid, probably due to their widespread use in recent years. Cases of suspected poisoning that involved exposure to rodenticides accounted for 27.6% of calls received by the MPCC and anticoagulant rodenticides were the primary cause of calls, with many cases involving brodifacoum and bromadiolone. Herbicides were involved in 14.2% of calls related to pesticides and glyphosate was the main culprit in cases involving dogs, cats, horses, goats and sheep. As far as exposure to molluscicides (11.5%) and fungicides (5.9%), most of the cases involved dogs and the suspected poisoning agents were metaldehyde and copper compounds respectively. The data collected are useful in determining trends in poisoning episodes and identifying newly emerging toxicants, thus demonstrating the prevalence of pesticides as causative agents in animal poisonings. Copyright © 2015 Elsevier B.V. All rights reserved.

Geographical characteristics influencing the risk of poisoning in pet dogs: Results of a large population-based epidemiological study in Italy.

PubMed

Calzetta, L; Roncada, P; Piras, C; Soggiu, A; Liccardi, G; Mattei, M; Pistocchini, E

2018-05-01

Pets can act as sentinels for human health and thus surveillance of pet dogs has the potential to improve awareness of emerging risks for animal and public health. The aim of this study was to investigate factors associated with the risk of canine poisoning. In a large population-based epidemiological investigation in Italy performed from January 2015 to January 2016 and April 2016 to April 2017, descriptive statistics were acquired and analysed to determine variables associated with poisoning events in pet dogs. Results were validated in a test population and forecast analysis of risk was performed. The cumulative incidence of poisoning events was low (10.2/1000 dogs/year). Anticoagulant rodenticides, organophosphate pesticides, metaldehyde and strychnine were the most frequent causes of intoxications. Territory characteristics significantly modulated both the frequency and the nature of the involved substances. The seashore area was associated with poisoning by rodenticides (odds ratio, OR, 1.81, 95% confidence interval, CI, 1.54-2.13) and metaldehyde (OR 1.61, 95% CI 1.16-2.28). The hill country area was associated with poisoning by organophosphate pesticides (OR 1.73, 95% CI 1.38-2.15), metaldehyde (OR 2.26, 95% CI 1.53-3.25) and strychnine (OR 1.86, 95% CI, 1.34-2.57). The mountain area was associated with strychnine poisoning (OR 3.79, 95% CI 2.84-5.06). The prospective cumulative incidence of poisoning over 10 years was 9.74% (95% CI 9.57-9.91). These results may be useful for predicting the risk of poisoning and for estimating the risk index related to specific toxic compounds in specific territories. This study suggests that poisoning events in dogs may represent a problem of public health with the potential to affect wildlife and human beings. Copyright © 2018 Elsevier Ltd. All rights reserved.

The bile sequestrant cholestyramine increases survival in a rabbit model of brodifacoum poisoning.

PubMed

Lindeblad, Matthew; Lyubimov, Alexander; van Breemen, Richard; Gierszal, Kamil; Weinberg, Guy; Rubinstein, Israel; Feinstein, Douglas L

2018-06-12

Patients exposed to long acting anticoagulant rodenticides (LAARs) are typically administered large amounts of oral vitamin K1 (VK1) to counteract life-threatening anti-coagulant effects. While 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 gm/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.

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

PubMed Central

Gabriel, Mourad W.; Woods, Leslie W.; Poppenga, Robert; Sweitzer, Rick A.; Thompson, Craig; Matthews, Sean M.; Higley, J. Mark; Keller, Stefan M.; Purcell, Kathryn; Barrett, Reginald H.; Wengert, Greta M.; Sacks, Benjamin N.; Clifford, Deana L.

2012-01-01

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. PMID:22808110

Assessment of toxicity and potential risk of the anticoagulant rodenticide diphacinone using Eastern screech-owls (Megascops asio).

PubMed

Rattner, Barnett A; Horak, Katherine E; Lazarus, Rebecca S; Eisenreich, Karen M; Meteyer, Carol U; Volker, Steven F; Campton, Christopher M; Eisemann, John D; Johnston, John J

2012-04-01

In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/or lethality at doses as low as 130 mg/kg body weight, although there was no dose-response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (<5%) of the acute oral dose. In the dietary trial, the average lowest-observed-adverse-effect-level for prolonged clotting time was 1.68 mg DPN/kg owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 μg/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3-5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian short-eared owl (Asio flammeus sandwichensis) and Hawaiian hawk (Buteo solitarius), and daily exposure to greater quantities (9-13 g of liver) could result in low-level mortality. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Assessment of toxicity and potential risk of the anticoagulant rodenticide diphacinone using Eastern screech-owls (Megascops asio)

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Lazarus, Rebecca S.; Eisenreich, Karen M.; Meteyer, Carol U.; Volker, Steven F.; Campton, Christopher M.; Eisemann, John D.; Johnston, John J.

2012-01-01

In the United States, new regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides. This action may be offset by expanded use of first-generation compounds (e.g., diphacinone; DPN). Single-day acute oral exposure of adult Eastern screech-owls (Megascops asio) to DPN evoked overt signs of intoxication, coagulopathy, histopathological lesions (e.g., hemorrhage, hepatocellular vacuolation), and/ or lethality at doses as low as 130 mg/kg body weight, although there was no dose-response relation. However, this single-day exposure protocol does not mimic the multiple-day field exposures required to cause mortality in rodent pest species and non-target birds and mammals. In 7-day feeding trials, similar toxic effects were observed in owls fed diets containing 2.15, 9.55 or 22.6 ppm DPN, but at a small fraction (<5%) of the acute oral dose. In the dietary trial, the average lowest-observed-adverse-effect-level for prolonged clotting time was 1.68 mg DPN/kg owl/week (0.24 mg/kg owl/day; 0.049 mg/owl/day) and the lowest lethal dose was 5.75 mg DPN/kg owl/week (0.82 mg/kg owl/day). In this feeding trial, DPN concentration in liver ranged from 0.473 to 2.21 μg/g wet weight, and was directly related to the daily and cumulative dose consumed by each owl. A probabilistic risk assessment indicated that daily exposure to as little as 3-5 g of liver from DPN-poisoned rodents for 7 days could result in prolonged clotting time in the endangered Hawaiian shorteared owl (Asio flammeus sandwichensis) and Hawaiian hawk (Buteo solitarius), and daily exposure to greater quantities (9-13 g of liver) could result in low-level mortality. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Pathogen and rodenticide exposure in American badgers (Taxidea taxus) in California.

PubMed

Quinn, Jessica H; Girard, Yvette A; Gilardi, Kirsten; Hernandez, Yvette; Poppenga, Robert; Chomel, Bruno B; Foley, Janet E; Johnson, Christine K

2012-04-01

Urban and agricultural land use may increase the risk of disease transmission among wildlife, domestic animals, and humans as we share ever-shrinking and fragmented habitat. American badgers (Taxidae taxus), a species of special concern in California, USA, live in proximity to urban development and often share habitat with livestock and small peridomestic mammals. As such, they may be susceptible to pathogens commonly transmitted at this interface and to anticoagulant rodenticides used to control nuisance wildlife on agricultural lands. We evaluated free-ranging badgers in California for exposure to pathogens and anticoagulant rodenticides that pose a risk to wildlife, domestic animals, or public health. We found serologic evidence of badger exposure to Francisella tularensis, Toxoplasma gondii, Anaplasma phagocytophilum, canine distemper virus, and three Bartonella species: B. henselae, B. clarridgeiae, and B. vinsonii subsp. berkhoffii. Badger tissues contained anticoagulant rodenticides brodifacoum and bromadiolone, commonly used to control periurban rodent pests. These data provide a preliminary investigation of pathogen and toxicant exposure in the wild badger population.

X-ray structures of the anticoagulants coumatetralyl and chlorophacinone. Theoretical calculations and SAR investigations on thirteen anticoagulant rodenticides

NASA Astrophysics Data System (ADS)

Dolmella, A.; Gatto, S.; Girardi, E.; Bandoli, G.

1999-12-01

Coumatetralyl and chlorophacinone, two substances related to 4-hydroxycoumarin (HC) and to 1,3-indandione (ID), respectively, show activity as anticoagulant rodenticides. In the present study we have investigated the solid-state structures of coumatetralyl and chlorophacinone by means of X-ray single-crystal and powder diffraction, along with thermal analysis. The crystal structures of the two compounds have been used as input geometries for a series of computational chemistry efforts, involving other anticoagulant derivatives as well. Thus, ab initio, semiempirical molecular orbital, molecular mechanics and molecular dynamics/simulated annealing calculations have been performed on thirteen anticoagulant rodenticides. In particular, the annealing calculations have been made to assess the conformational freedom of the compounds under scrutiny. All the generated conformers have been classified into families. The classification has first been made empirically, and then validated by means of a cluster analysis. A number of structural and physico-chemical parameters derived from the calculations has been used in turn for structure-activity relationships (SARs) investigations. In the latter, we have assessed how the selected parameters affect toxicity. The results seem to be consistent with a three-dimensional biophore model, in which higher toxicity is predicted for the more voluminous rodenticides. We suggest that these compounds better fit the active site of the target enzyme vitamin K 2,3-epoxide reductase (KO-reductase).

VIGILANCE POISON: Illegal poisoning and lead intoxication are the main factors affecting avian scavenger survival in the Pyrenees (France).

PubMed

Berny, Philippe; Vilagines, Lydia; Cugnasse, Jean-Marc; Mastain, Olivier; Chollet, Jean-Yves; Joncour, Guy; Razin, Martine

2015-08-01

A specific surveillance program has been set up to monitor avian scavenger populations in the French Pyrenean Mountains, hosting a high proportion of the French populations. The two main purposes of the study were to identify all causes of death and to investigate poisoning cases. All 170 birds found dead during the 7-year program were submitted to full necropsy, X-Ray, parasitological investigations and consistent analytical toxicology screenings (Cholinesterase inhibitors, anticoagulant rodenticides, organochlorine insecticides, Pb, Cd). Over the study period, 8 Bearded Vultures, 120 Griffon Vultures, 8 Egyptian Vultures and 34 Red kites were eventually collected. Mortality events were often multifactorial, but poisoning was by far the most common cause of death (24.1%), followed by trauma/fall (12%), bacterial diseases and starvation (8%) and electrocution (6%). Illicit use of banned pesticides was identified as a common cause of poisoning (53% of all poisoning cases) and lead poisoning was also identified as a significant toxicant issue (17% of all poisoning cases). Lead isotopic signature could be associated primarily with ammunition. Last, a positive association between trauma and lead contamination was detected, indicating that lead could be a significant contributor to different causes of death. These results urge for severe restrictions on the use of lead ammunition to prevent scavengers from detrimental exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

Land use as a Driver of Patterns of Rodenticide Exposure in Modeled Kit Fox Populations

EPA Science Inventory

Although rodenticides are increasingly regulated, they nonetheless cause poisonings in many non-target wildlife species. Second-generation anticoagualant rodenticide use is common in agricultural and residential lands. Here, we use an individual-based population model to assess t...

Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

USGS Publications Warehouse

Vyas, Nimish B.; Rattner, Barnett A.

2012-01-01

Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

Mortality of Western Burrowing Owls ( Athene cunicularia hypugaea) Associated with Brodifacoum Exposure.

PubMed

Justice-Allen, Anne; Loyd, Kerrie Anne

2017-01-01

Western Burrowing Owls ( Athene cunicularia hypugaea) frequently occupy periurban areas, where they may be exposed to pest control agents. This short communication describes necropsy findings and detected brodifacoum rodenticide levels for four Western Burrowing Owls in Lake Havasu City, Arizona, US, 2013-15. Levels detected ranged from 0.077 mg/kg to 0.497 mg/kg. Brodifacoum, one of several second-generation anticoagulant rodenticides recently removed from the general consumer market, is still available for use by licensed pesticide applicators. Despite recent regulatory actions, second-generation anticoagulant pesticides continue to threaten predatory species in periurban areas.

Efficacy of rodenticide baits for the control of three invasive rodent species in Hawaii.

PubMed

Pitt, William C; Driscoll, Laura C; Sugihara, Robert T

2011-04-01

We tested the efficacy and palatability of nine commercial rodenticide bait formulations on Polynesian rats (Rattus exulans), roof rats (R. rattus), and house mice (Mus musculus). Efficacy varied by rodenticide tested and rodent species. Generally, rodenticides were more effective against mice than for either of the rat species, and mice tended to consume more rodenticide bait than the laboratory chow alternative food. Efficacy was generally highest for the second-generation anticoagulants tested; however, this varied across products and one-first-generation rodenticide had similar effectiveness. Bait acceptance (palatability) also varied both by rodenticide and by rodent species. Acceptance was the lowest for the acute rodenticides. Bait acceptance appeared to substantially affect the efficacy of rodenticides; materials that were not well accepted produced lower mortality rates. Rodenticide products currently registered for use in Hawaii performed less effectively in this study than other available products not yet registered. Although markets for rodent control products for use on islands are limited, there are advantages to having additional products registered for island use in agriculture, conservation, and public health. © US Government 2010

Relation between Intensity of Biocide Practice and Residues of Anticoagulant Rodenticides in Red Foxes (Vulpes vulpes)

PubMed Central

Geduhn, Anke; Jacob, Jens; Schenke, Detlef; Keller, Barbara; Kleinschmidt, Sven; Esther, Alexandra

2015-01-01

Anticoagulant rodenticides (ARs) are commonly used to control rodent infestations for biocidal and plant protection purposes. This can lead to AR exposure of non-target small mammals and their predators, which is known from several regions of the world. However, drivers of exposure variation are usually not known. To identify environmental drivers of AR exposure in non-targets we analyzed 331 liver samples of red foxes (Vulpes vulpes) for residues of eight ARs and used local parameters (percentage of urban area and livestock density) to test for associations to residue occurrence. 59.8% of samples collected across Germany contained at least one rodenticide, in 20.2% of cases at levels at which biological effects are suspected. Second generation anticoagulants (mainly brodifacoum and bromadiolone) occurred more often than first generation anticoagulants. Local livestock density and the percentage of urban area were good indicators for AR residue occurrence. There was a positive association between pooled ARs and brodifacoum occurrence with livestock density as well as of pooled ARs, brodifacoum and difenacoum occurrence with the percentage of urban area on administrative district level. Pig holding drove associations of livestock density to AR residue occurrence in foxes. Therefore, risk mitigation strategies should focus on areas of high pig density and on highly urbanized areas to minimize non-target risk. PMID:26418154

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

PubMed

Lee, Hee-Jeong; You, Mi-Ra; Moon, Woo-Ram; Sul, Hyoung; Chung, Choon-Hae; Park, Chi-Young; Park, Sang-Gon

2014-07-01

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

Influence of poisoned prey on foraging behavior of ferruginous hawks

USGS Publications Warehouse

Vyas, Nimish B.; Kuncir, Frank; Clinton, Criss C.

2017-01-01

We recorded 19 visits by ferruginous hawks (Buteo regalis) over 6 d at two black–tailed prairie dog (Cynomys ludovicianus) subcolonies poisoned with the rodenticide Rozol® Prairie Dog Bait (0.005% chlorophacinone active ingredient) and at an adjacent untreated subcolony. Before Rozol® application ferruginous hawks foraged in the untreated and treated subcolonies but after Rozol® application predation by ferruginous hawks was only observed in the treated subcolonies. We suggest that ferruginous hawks' preference for hunting in the treated subcolonies after Rozol® application was influenced by the availability of easy-to-capture prey, presumably due to Rozol® poisoning. The energetically beneficial behavior of favoring substandard prey may increase raptor encounters with rodenticide exposed animals if prey vulnerability has resulted from poisoning.

Plasma metabolic profiling analysis of toxicity induced by brodifacoum using metabonomics coupled with multivariate data analysis.

PubMed

Yan, Hui; Qiao, Zheng; Shen, Baohua; Xiang, Ping; Shen, Min

2016-10-01

Brodifacoum is one of the most widely used rodenticides for rodent control and eradication; however, human and animal poisoning due to primary and secondary exposure has been reported since its development. Although numerous studies have described brodifacoum induced toxicity, the precise mechanism still needs to be explored. Gas chromatography mass spectrometry (GC-MS) coupled with an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was applied to characterize the metabolic profile of brodifacoum induced toxicity and discover potential biomarkers in rat plasma. The toxicity of brodifacoum was dose-dependent, and the high-dose group obviously manifested toxicity with subcutaneous hemorrhage. The blood brodifacoum concentration showed a positive relation to the ingestion dose in toxicological analysis. Significant changes of twenty-four metabolites were identified and considered as potential toxicity biomarkers, primarily involving glucose metabolism, lipid metabolism and amino acid metabolism associated with anticoagulant activity, nephrotoxicity and hepatic damage. MS-based metabonomics analysis in plasma samples is helpful to search for potential poisoning biomarkers and to understand the underlying mechanisms of brodifacoum induced toxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparative risk assessment of the first-generation anticoagulant rodenticide diphacinone to raptors

USGS Publications Warehouse

Rattner, Barnett A.; Lazarus, Rebecca S.; Eisenreich, Karen M.; Horak, Katherine E.; Volker, Steven F.; Campton, Christopher M.; Eisemann, John D.; Meteyer, Carol U.; Johnson, John J.

2012-01-01

New regulatory restrictions have been placed on the use of some second-generation anticoagulant rodenticides in the United States, and in some situations this action may be offset by expanded use of first-generation compounds. We have recently conducted several studies with captive adult American kestrels and eastern screech-owls examining the toxicity of diphacinone (DPN) using both acute oral and short-term dietary exposure regimens. Diphacinone evoked overt signs of intoxication and lethality in these raptors at exposure doses that were 20 to 30 times lower than reported for traditionally used wildlife test species (mallard and northern bobwhite). Sublethal exposure of kestrels and owls resulted in prolonged clotting time, reduced hematocrit, and/or gross and histological evidence of hemorrhage at daily doses as low as 0.16 mg DPN/kg body weight. Findings also demonstrated that DPN was far more potent in short-term 7-day dietary studies than in single-day acute oral exposure studies. Incorporating these kestrel and owl data into deterministic and probabilistic risk assessments indicated that the risks associated with DPN exposure for raptors are far greater than predicted in analyses using data from mallards and bobwhite. These findings can assist natural resource managers in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Arsenic exposures in Mississippi: A review of cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, M.J.; Currier, M.

Arsenic poisonings occur in Mississippi despite public education campaigns to prevent poisonings in the home. We reviewed 44 Mississippi cases of arsenic exposures occurring from January 1986 to May 1990. We compared the epidemiologic differences between unintentional and intentional poisonings. Cases were found and characterized through the two toxicology laboratories and hospital records. Arsenic-based rodenticides were the arsenic source in 23 of the 44 exposures. Other sources were monosodium methylarsenate (4 cases), dodecyl ammonium methane arsonate (5 cases), and other compounds (12 cases). Of the 44 exposures, 27 were unintentional, 7 were suicide attempts, 6 were homicide attempts, and 4more » were of unknown intent. Of the 27 unintentionally exposed patients, 19 were black and 14 were male; their median age was 3 years. Of the 13 intentionally poisoned persons, 9 were male and 10 were black, with a median age of 28 years. Six of the seven patients who attempted suicide were white; four of the six victims of attempted homicide were black. We recommend removal of remaining bottles of arsenic-based rodenticides from store shelves, and we urge practicing physicians to warn patients of the dangers of using such rodenticides.« less

Laboratory trials of seven rodenticides for use against the cotton rat (Sigmodon hispidus).

PubMed Central

Gill, J. E.; Redfern, R.

1980-01-01

The efficacy of seven rodenticides for use against Sigmodon hispidus was investigated in the laboratory. The poisons (warfarin, coumatetralyl, difenacoum, brodifacoum, bromadiolone, calciferol and zinc phosphide) were all toxic at the concentrations normally used against Rattus rattus and R. norvegicus and all were palatable. Trials are now needed to confirm the efficacy of these poisons in the field, but it seems likely that, if used in suitable bait formulations, they would all be useful for the practical control of S. hispidus. PMID:7462594

A profile of unintentional poisoning caused by household cleaning products, disinfectants and pesticides.

PubMed

Presgrave, Rosaura de Farias; Camacho, Luiz Antônio Bastos; Villas Boas, Maria Helena Simões

2008-12-01

Unintentional poisoning occurred mainly among children. The leading cause of such poisoning in Brazil, among consumer products was household cleaning products. For this study 2810 calls made to two poison control centers in the State of Rio de Janeiro between January 2000 and December 2002 were analyzed. Children under five were the most vulnerable group. More boys under 10 suffered accidental poisoning than girls, although above this age, the distribution was inverted. The calls received by poison control centers were mainly from health services within the first two hours following poisoning. The most frequent exposure routes were ingestion (90.4%), followed by inhalation (4.3%), skin and eye contact (2.4% and 2% respectively). The products involved were bleach, petroleum derivates, rodenticides and pesticides. The main causes were products within the children's reach, storage in soft drink bottles, food mixed with rodenticides, incorrect product use, and kitchen utensils used for measured cleaning products. The most common outcome was that the patient was cured, although a lot of cases were lost to follow-up. Education programs are necessary in order to avoid these poisonings.

PRN 66 Federal Registration of Economic Poisons

EPA Pesticide Factsheets

The Federal Insecticide, Fungicide, and Rodenticide Act, and the regulations promulgated thereunder, provide that an economic poison is misbranded if its labeling bears any statement, graphic representation, or design which is false or misleading.

Anticoagulant rodenticide exposure and toxicosis in four species of birds of prey in Massachusetts, USA, 2012-2016, in relation to use of rodenticides by pest management professionals.

PubMed

Murray, Maureen

2017-10-01

Restrictions on second-generation anticoagulant rodenticides (SGARs) in the United States, which were partially implemented in 2011, prohibit the sale of SGAR products through general consumer outlets to minimize use by non-professional or non-agricultural applicators. This study analyzed liver tissue from four species of birds of prey admitted to a wildlife clinic in Massachusetts, USA, from 2012-2016 for residues of anticoagulant rodenticides (ARs). Ninety-four birds were analyzed; 16 were symptomatic for AR toxicosis, and 78 asymptomatic. Ninety-six percent of all birds tested were positive for SGARs: 100% of those diagnosed with AR toxicosis ante-mortem and/or post-mortem and 95% of subclinically exposed birds. Brodifacoum was found in 95% of all birds. Sixty-six percent of all birds contained residues of two or more SGARs. A significant increase in exposures to multiple SGARs occurred in later years in the study. Pesticide use reports (PURs) filed with the Massachusetts Department of Agricultural Resources were reviewed to determine the frequency of use of different ARs by pest management professionals (PMPs) across five years. This study finds that the three SGARs favored by PMPs-bromadiolone, difethialone, brodifacoum-were present in combination in the majority of birds, with increases in multiple exposures driven by increased detections of bromadiolone and difethialone. Continued monitoring of AR residues in nontarget species following full implementation of sales and packaging restrictions in the US is needed in order to elucidate the role of PMP use of SGARs in wildlife exposures and to evaluate the effectiveness of current mitigation measures.

Acute toxicity of diphacinone in Northern bobwhite: Effects on survival and blood clotting

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Johnston, John J.

2010-01-01

The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell?s Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.

Options for Dealing With Rodent Infestations

EPA Pesticide Factsheets

After removing sources of food and water and shelter, your next options are rodent traps and poisons (rodenticides). Rat or mouse traps may be lethal (snap traps) or live (cage-type), and poison baits must be placed in tamper-resistant bait stations.

Prey composition modulates exposure risk to anticoagulant rodenticides in a sentinel predator, the barn owl.

PubMed

Geduhn, Anke; Esther, Alexandra; Schenke, Detlef; Gabriel, Doreen; Jacob, Jens

2016-02-15

Worldwide, small rodents are main prey items for many mammalian and avian predators. Some rodent species have pest potential and are managed with anticoagulant rodenticides (ARs). ARs are consumed by target and non-target small mammals and can lead to secondary exposure of predators. The development of appropriate risk mitigation strategies is important and requires detailed knowledge of AR residue pathways. From July 2011 to October 2013 we collected 2397 regurgitated barn owl (Tyto alba) pellets to analyze diet composition of owls on livestock farms in western Germany. 256 of them were fresh pellets that were collected during brodifacoum baiting. Fresh pellets and 742 liver samples of small mammals that were trapped during baiting in the same area were analyzed for residues of ARs. We calculated exposure risk of barn owls to ARs by comparing seasonal diet composition of owls with AR residue patterns in prey species. Risk was highest in autumn, when barn owls increasingly preyed on Apodemus that regularly showed AR residues, sometimes at high concentrations. The major prey species (Microtus spp.) that was consumed most frequently in summer had less potential to contribute to secondary poisoning of owls. There was no effect of AR application on prey composition. We rarely detected ARs in pellets (2 of 256 samples) but 13% of 38 prey individuals in barn owl nests were AR positive and substantiated the expected pathway. AR residues were present in 55% of 11 barn owl carcasses. Fluctuation in non-target small mammal abundance and differences in AR residue exposure patterns in prey species drives exposure risk for barn owls and probably other predators of small mammals. Exposure risk could be minimized through spatial and temporal adaption of AR applications (avoiding long baiting and non-target hot spots at farms) and through selective bait access for target animals. Copyright © 2015 Elsevier B.V. All rights reserved.

Assessment of toxicity and coagulopathy of brodifacoum in Japanese quail and testing in wild owls.

PubMed

Webster, Kirstin H; Harr, Kendal E; Bennett, Darin C; Williams, Tony D; Cheng, Kimberly M; Maisonneuve, France; Elliott, John E

2015-07-01

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.

Simultaneous determination of seven anticoagulant rodenticides in agricultural products by gel permeation chromatography and liquid chromatography-tandem mass spectrometry.

PubMed

Saito-Shida, Shizuka; Nemoto, Satoru; Matsuda, Rieko; Akiyama, Hiroshi

2016-11-01

A sensitive and reliable method for the simultaneous determination of hydroxycoumarin-type (brodifacoum, bromadiolone, coumatetralyl, and warfarin) and indandione-type (chlorophacinone, diphacinone, and pindone) rodenticides in agricultural products by gel permeation chromatography (GPC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. The procedure involved extraction of the rodenticides from samples with acetone, followed by liquid-liquid partitioning with hexane/ethyl acetate (1:1, v/v) and 10% sodium chloride aqueous solution, then cleanup using GPC, and finally, analysis using LC-MS/MS. High recoveries from the GPC column were obtained for all rodenticides tested using a mobile phase of acetone/cyclohexane/triethylamine (400:1600:1, v/v/v). An ODS column, which contains low levels of metal impurities, gave satisfactory peak shapes for both hydroxycoumarin- and indandione-type rodenticides in the LC-MS/MS separation. The average recoveries of rodenticides from eight agricultural foods (apple, eggplant, cabbage, orange, potato, tomato, brown rice, and soybean) fortified at 0.0005-0.001 mg/kg ranged from 76 to 116%, except for bromadiolone in orange (53%) and diphacinone in soybean (54%), and the relative standard deviations ranged from 1 to 16%. The proposed method effectively removed interfering components, such as pigments and lipids, and showed high selectivity. In addition, the matrix effects were negligible for most of the rodenticide/food combinations. The results suggest that the proposed method is reliable and suitable for determining hydroxycoumarin- and indandione-type rodenticides in agricultural products.

The emerging threat of superwarfarins: history, detection, mechanisms, and countermeasures: The emerging threat of superwarfarins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feinstein, Douglas L.; Akpa, Belinda S.; Ayee, Manuela A.

Superwarfarins were developed following the emergence of warfarin resistance in rodents. Compared to warfarin, superwarfarins have much longer half-lives and stronger affinity to vitamin K epoxide reductase and therefore can cause death in warfarin-resistant rodents. By the mid-1970s, the superwarfarins brodifacoum and difenacoum were the most widely used rodenticides throughout the world. Unfortunately, increased use was accompanied by a rise in accidental poisonings, reaching >16,000 per year in the United States. Risk of exposure has become a concern since large quantities, up to hundreds of kilograms of rodent bait, are applied by aerial dispersion over regions with rodent infestations. Reportsmore » of intentional use of superwarfarins in civilian and military scenarios raise the specter of larger incidents or mass casualties. Unlike warfarin overdose, for which 1–2 days of treatment with vitamin K is effective, treatment of superwarfarin poisoning with vitamin K is limited by extremely high cost and can require daily treatment for a year or longer. Furthermore, superwarfarins have actions that are independent of their anticoagulant effects, including both vitamin K–dependent and –independent effects,which are not mitigated by vitaminKtherapy. In this review, we summarize superwarfarin development, biology and pathophysiology, their threat as weapons, and possible therapeutic approaches.« less

The emerging threat of superwarfarins: history, detection, mechanisms, and countermeasures

PubMed Central

Feinstein, Douglas L.; Akpa, Belinda S.; Ayee, Manuela A.; Boullerne, Anne I.; Braun, David; Brodsky, Sergey V.; Gidalevitz, David; Hauck, Zane; Kalinin, Sergey; Kowal, Kathy; Kuzmenko, Ivan; Lis, Kinga; Marangoni, Natalia; Martynowycz, Michael W.; Rubinstein, Israel; van Breemen, Richard; Ware, Kyle; Weinberg, Guy

2016-01-01

Superwarfarins were developed following the emergence of warfarin resistance in rodents. Superwarfarins have much longer half-lives and stronger affinity to vitamin K epoxide reductase versus warfarin, and therefore can cause death in warfarin-resistant rodents. By the mid-1970s, the superwarfarins brodifacoum (BDF) and difenacoum (DiF) were the most widely used rodenticides throughout the world. Unfortunately, increased use was accompanied by a rise in accidental poisonings, reaching >16,000 per year in the United States. Risk of exposure has become a concern since large quantities, up to hundreds of kilograms of rodent bait, are applied by aerial dispersion over regions with rodent infestations. Reports of intentional use of superwarfarins in civilian and military scenarios raises the specter of larger incidents or mass casualties. Unlike warfarin overdose, for which 1–2 days of treatment with vitamin K is effective, treatment of superwarfarin poisoning with vitamin K is limited by extremely high cost and can require daily treatment for a year or longer. Furthermore, superwarfarins have actions that are independent of their anticoagulant effects, including both vitamin K–dependent and –independent effects, which are not mitigated by vitamin K therapy. In this review, we will summarize superwarfarin development, biology and pathophysiology, their threat as weapons, and possible therapeutic approaches. PMID:27244102

Diazinon poisoning

MedlinePlus

Cannon RD, Ruha A-M. Insecticides, herbicides, and rodenticides. In: Adams JG, ed. Emergency Medicine . 2nd ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 146. Welker K, Thompson TM. Pesticides. ...

Insecticide poisoning

MedlinePlus

Cannon RD, Ruha A-M. Insecticides, herbicides, and rodenticides. In: Adams JG, ed. Emergency Medicine . 2nd ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 146. Welker K, Thompson TM. Pesticides. ...

Adverse outcome pathway and risks of anticoagulant rodenticides to predatory wildlife

USGS Publications Warehouse

Rattner, Barnett A.; Lazarus, Rebecca S.; Elliott, John E.; Shore, Richard F.; van den Brink, Nico

2014-01-01

Despite a long history of successful use, routine application of some anticoagulant rodenticides (ARs) may be at a crossroad due to new regulatory guidelines intended to mitigate risk. An adverse outcome pathway for ARs was developed to identify information gaps and end points to assess the effectiveness of regulations. This framework describes chemical properties of ARs, established macromolecular interactions by inhibition of vitamin K epoxide reductase, cellular responses including altered clotting factor processing and coagulopathy, organ level effects such as hemorrhage, organism responses with linkages to reduced fitness and mortality, and potential consequences to predator populations. Risk assessments have led to restrictions affecting use of some second-generation ARs (SGARs) in North America. While the European regulatory community highlighted significant or unacceptable risk of ARs to nontarget wildlife, use of SGARs in most EU member states remains authorized due to public health concerns and the absence of safe alternatives. For purposes of conservation and restoration of island habitats, SGARs remain a mainstay for eradication of invasive species. There are significant data gaps related to exposure pathways, comparative species sensitivity, consequences of sublethal effects, potential hazards of greater AR residues in genetically resistant prey, effects of low-level exposure to multiple rodenticides, and quantitative data on the magnitude of nontarget wildlife mortality.

Bug spray poisoning

MedlinePlus

Cannon RD, Ruha A-M. Insecticides, herbicides, and rodenticides. In: Adams JG, ed. Emergency Medicine: Clinical Essentials . 2nd ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 146. Freedman DO. Protection ...

An epidemiological study of poisoning in northern Islamic Republic of Iran.

PubMed

Moghadamnia, A A; Abdollahi, M

2002-01-01

We examined the causes and mortality of poisoning in the province of Mazandaran. In all, 1751 poisoning cases referred to four main hospitals over a three-year period (1997-2000) were included. More poisoning cases were females (55.5%) than males (45.5%) but the proportional mortality for males was greater than for females (65% versus 35%). The greatest proportion of poisonings occurred between the ages of 16 and 25 years. Most frequent was intentional poisoning, followed by accidental and occupational poisoning. Medicines were the most common cause, followed by chemicals such as pesticides. Poisoning by opiates, aluminium or zinc phosphide, rodenticides, petroleum and ethanol intoxication was also observed. Pesticide poisoning was most frequently fatal.

Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population

PubMed Central

Gasqui, Patrick; Cosson, Jean-François; Benoît, Etienne; Lattard, Virginie; Crespin, Laurent; Lorvelec, Olivier; Pisanu, Benoît; Teynié, Alexandre; Vayssier-Taussat, Muriel; Bonnet, Sarah; Marianneau, Philippe; Lacôte, Sandra; Bourhy, Pascale; Berny, Philippe; Pavio, Nicole; Le Poder, Sophie; Gilot-Fromont, Emmanuelle; Jourdain, Elsa; Hammed, Abdessalem; Fourel, Isabelle; Chikh, Farid; Vourc’h, Gwenaël

2017-01-01

Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park. PMID:28886097

Population genetics, community of parasites, and resistance to rodenticides in an urban brown rat (Rattus norvegicus) population.

PubMed

Desvars-Larrive, Amélie; Pascal, Michel; Gasqui, Patrick; Cosson, Jean-François; Benoît, Etienne; Lattard, Virginie; Crespin, Laurent; Lorvelec, Olivier; Pisanu, Benoît; Teynié, Alexandre; Vayssier-Taussat, Muriel; Bonnet, Sarah; Marianneau, Philippe; Lacôte, Sandra; Bourhy, Pascale; Berny, Philippe; Pavio, Nicole; Le Poder, Sophie; Gilot-Fromont, Emmanuelle; Jourdain, Elsa; Hammed, Abdessalem; Fourel, Isabelle; Chikh, Farid; Vourc'h, Gwenaël

2017-01-01

Brown rats are one of the most widespread urban species worldwide. Despite the nuisances they induce and their potential role as a zoonotic reservoir, knowledge on urban rat populations remains scarce. The main purpose of this study was to characterize an urban brown rat population from Chanteraines park (Hauts-de-Seine, France), with regards to haematology, population genetics, immunogenic diversity, resistance to anticoagulant rodenticides, and community of parasites. Haematological parameters were measured. Population genetics was investigated using 13 unlinked microsatellite loci. Immunogenic diversity was assessed for Mhc-Drb. Frequency of the Y139F mutation (conferring resistance to rodenticides) and two linked microsatellites were studied, concurrently with the presence of anticoagulant residues in the liver. Combination of microscopy and molecular methods were used to investigate the occurrence of 25 parasites. Statistical approaches were used to explore multiple parasite relationships and model parasite occurrence. Eighty-six rats were caught. The first haematological data for a wild urban R. norvegicus population was reported. Genetic results suggested high genetic diversity and connectivity between Chanteraines rats and surrounding population(s). We found a high prevalence (55.8%) of the mutation Y139F and presence of rodenticide residues in 47.7% of the sampled individuals. The parasite species richness was high (16). Seven potential zoonotic pathogens were identified, together with a surprisingly high diversity of Leptospira species (4). Chanteraines rat population is not closed, allowing gene flow and making eradication programs challenging, particularly because rodenticide resistance is highly prevalent. Parasitological results showed that co-infection is more a rule than an exception. Furthermore, the presence of several potential zoonotic pathogens, of which four Leptospira species, in this urban rat population raised its role in the maintenance and spread of these pathogens. Our findings should stimulate future discussions about the development of a long-term rat-control management program in Chanteraines urban park.

Grass and weed killer poisoning

MedlinePlus

Cannon RD, Ruha A-M. Insecticides, herbicides, and rodenticides. In: Adams JG, ed. Emergency Medicine . 2nd ed. Philadelphia, PA: Elsevier Saunders; 2013:chap 146. Welker K, Thompson TM. Pesticides. ...

Locus-specific genetic differentiation at Rw among warfarin-resistant rat (Rattus norvegicus) populations.

PubMed Central

Kohn, Michael H; Pelz, Hans-Joachim; Wayne, Robert K

2003-01-01

Populations may diverge at fitness-related genes as a result of adaptation to local conditions. The ability to detect this divergence by marker-based genomic scans depends on the relative magnitudes of selection, recombination, and migration. We survey rat (Rattus norvegicus) populations to assess the effect that local selection with anticoagulant rodenticides has had on microsatellite marker variation and differentiation at the warfarin resistance gene (Rw) relative to the effect on the genomic background. Initially, using a small sample of 16 rats, we demonstrate tight linkage of microsatellite D1Rat219 to Rw by association mapping of genotypes expressing an anticoagulant-rodenticide-insensitive vitamin K 2,3-epoxide reductase (VKOR). Then, using allele frequencies at D1Rat219, we show that predicted and observed resistance levels in 27 populations correspond, suggesting intense and recent selection for resistance. A contrast of F(ST) values between D1Rat219 and the genomic background revealed that rodenticide selection has overwhelmed drift-mediated population structure only at Rw. A case-controlled design distinguished these locus-specific effects of selection at Rw from background levels of differentiation more effectively than a population-controlled approach. Our results support the notion that an analysis of locus-specific population genetic structure may assist the discovery and mapping of novel candidate loci that are the object of selection or may provide supporting evidence for previously identified loci. PMID:12871915

Comparative toxicity of diphacinone to northern bobwhite (Colinus virginianus) and American kestrels (Falco sparverius)

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Johnston, John J.

2010-01-01

The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be about 20 times greater to American kestrels (LD50=97 mg/kg) than to northern bobwhite (LD50=2,014 mg/kg). Several precise and sensitive clotting assays (prothrombin time, Russell's Viper venom time, thrombin clotting time) were adapted for use in these species, and this combination of assays is recommended to detect effects of diphacinone and other rodenticides on coagulation. Oral administration of diphacinone over a range of doses (sublethal to the extrapolated LD15) prolonged prothrombin time and Russell's Viper venom time within 24 to 48 hrs post-exposure. Prolongation of in vitro clotting time reflects impaired coagulation complex activity and was detected before or at the onset of overt signs of toxicity and lethality. These data will assist in the development of a pharmacodynamic model to assess and predict rodenticide toxicity to non-target avian species.

Restrictions on Rodenticide Products

EPA Pesticide Factsheets

Consumer size products contain one pound of poison bait or less and must include a bait station. Products formulated for pest control professionals also meet certain requirements. Read the product label to ensure safe and effective use.

Mouse and rat poisons in pellet form banned

EPA Pesticide Factsheets

EPA has been working with manufacturers to ensure that safer rodenticide products are available to consumers for use in controlling rodents in the house. Find out more about how to find safer products.

EPIDEMIOLOGY OF ACCIDENTAL POISONING

PubMed Central

Bissell, D. M.; McInnes, Robert S.

1960-01-01

In San Jose, California, studies of cases of accidental poisoning showed that the greatest hazard was to children 1 through 3 years of age. Drugs accounted for half the cases, household products for another third, and insecticides and rodenticides and others for the remainder. Most often poison material was within easy reach of the children. An analysis of families in which an accident occurred indicated that accidental poisoning might happen to any family. Since there was little after-effect of poisoning in cases in which treatment was obtained promptly, education directed toward getting prompt treatment seems most advisable. Community agencies interested in poison control need to focus their attention on parents of pre-school children. PMID:13801023

Safely Use Rodent Bait Products

EPA Pesticide Factsheets

Rat and mouse poison products, if misused, can potentially harm you, your children, or your pets. Always read the product label and follow all directions. Choose safe rodenticide products, store pesticides properly, and use bait stations appropriately.

Field trials of the rodenticide gophacide against wild house mice (Mus musculus L.).

PubMed Central

Rowe, F. P.; Swinney, T.; Bradfield, A.

1975-01-01

The acute rodenticide gophacide was tested against urban infestations of the house mouse (Mus musculus L.) and treatment success was assessed from the results of census baitings conducted before and after each treatment. Seven of eight populations of mice living in premises where alternative food supplies were limited were successfully controlled when medium oatmeal bait containing gophacide at 0.1% was laid directly for 4 days. In further treatments against mice inhabiting more complex environments and having greater access to other foods, the performance of gophacide at 0.1% and at 0.25% in a wholemeal flour/pinhead oatmeal/corn oil bait was compared with that of zinc phosphide at 3.0% in the same bait-base. The poison treatments were conducted for 1 or 4 days and always after 3 days pre-baiting. Treatment success varied considerably irrespective of the type of treatment or of the poison used. In general, however, gophacide proved to be as effective as zinc phosphide for the control of mice. PMID:1054056

Accidental discharge of brodifacoum baits into a freshwater lake: a case study.

PubMed

Fisher, P; Funnell, E; Fairweather, A; Brown, L; Campion, M

2012-02-01

Approximately 700 kg of cereal bait containing 20 ppm of the anticoagulant rodenticide brodifacoum was spilled into a southern New Zealand lake in 2010 from a helicopter being used to transport containers of brodifacoum bait for an aerial baiting operation. In the month after the spill no residual brodifacoum was detected in samples of lake water, sediment, benthic invertebrates, eels, and two birds.

Toxicity reference values for chlorophacinone and their application for assessing anticoagulant rodenticide risk to raptors.

PubMed

Rattner, Barnett A; Horak, Katherine E; Lazarus, Rebecca S; Schultz, Sandra L; Knowles, Susan; Abbo, Benjamin G; Volker, Steven F

2015-05-01

Despite widespread use and benefit, there are growing concerns regarding hazards of second-generation anticoagulant rodenticides to non-target wildlife which may result in expanded use of first-generation compounds, including chlorophacinone (CPN). The toxicity of CPN over a 7-day exposure period was investigated in American kestrels (Falco sparverius) fed either rat tissue mechanically-amended with CPN, tissue from rats fed Rozol(®) bait (biologically-incorporated CPN), or control diets (tissue from untreated rats or commercial bird of prey diet) ad libitum. Nominal CPN concentrations in the formulated diets were 0.15, 0.75 and 1.5 µg/g food wet weight, and measured concentrations averaged 94 % of target values. Kestrel food consumption was similar among groups and body weight varied by less than 6 %. Overt signs of intoxication, liver CPN residues, and changes in prothrombin time (PT), Russell's viper venom time (RVVT) and hematocrit, were generally dose-dependent. Histological evidence of hemorrhage was present at all CPN dose levels, and most frequently observed in pectoral muscle and heart. There were no apparent differences in toxicity between mechanically-amended and biologically-incorporated CPN diet formulations. Dietary-based toxicity reference values at which clotting times were prolonged in 50 % of the kestrels were 79.2 µg CPN consumed/kg body weight-day for PT and 39.1 µg/kg body weight-day for RVVT. Based upon daily food consumption of kestrels and previously reported CPN concentrations found in small mammals following field baiting trials, these toxicity reference values might be exceeded by free-ranging raptors consuming such exposed prey. Tissue-based toxicity reference values for coagulopathy in 50 % of exposed birds were 0.107 µg CPN/g liver wet weight for PT and 0.076 µg/g liver for RVVT, and are below the range of residue levels reported in raptor mortality incidents attributed to CPN exposure. Sublethal responses associated with exposure to environmentally realistic concentrations of CPN could compromise survival of free-ranging raptors, and should be considered in weighing the costs and benefits of anticoagulant rodenticide use in pest control and eradication programs.

Tetramethylenedisulfotetramine: pest control gone awry.

PubMed

Shakarjian, Michael P; Laukova, Marcela; Velíšková, Jana; Stanton, Patric K; Heck, Diane E; Velíšek, Libor

2016-08-01

Incidences of pesticide poisonings are a significant cause of morbidity and mortality worldwide. The seizure-inducing rodenticide tetramethylenedisulfotetramine is one of the most toxic of these agents. Although banned, it has been responsible for thousands of accidental, intentional, and mass poisonings in mainland China and elsewhere. An optimal regimen for treatment of poisoning has not been established. Its facile synthesis from easily obtained starting materials, extreme potency, and lack of odor, color, or taste make it a potential chemical threat agent. This review describes the toxicologic properties of this agent, more recent advances in our understanding of its properties, and recommendations for future research. © 2016 New York Academy of Sciences.

Toxicokinetics and coagulopathy threshold of the rodenticide diphacinone in eastern screech-owls (Megascops asio)

USGS Publications Warehouse

Rattner, Barnett A.; Horak, K.E.; Lazarus, Rebecca S.; Goldade, D.A.; Johnston, J.J.

2014-01-01

In the United States, new regulations on second-generation anticoagulant rodenticides will likely be offset by expanded use of first-generation anticoagulant rodenticides. In the present study, eastern screech-owls (Megascops asio) were fed 10 µg diphacinone/g wet weight food for 7 d, and recovery was monitored over a 21-d postexposure period. By day 3 of exposure, diphacinone (DPN) was detected in liver (1.63 µg/g wet wt) and kidney (5.83 µg/g) and coagulopathy was apparent. By day 7, prothrombin time (PT) and Russell's viper venom time (RVVT) were prolonged, and some individuals were anemic. Upon termination of exposure, coagulopathy and anemia were resolved within 4 d, and residues decreased to <0.3 µg/g by day 7. Liver and kidney DPN elimination occurred in 2 phases (initial rapid loss, followed by slower loss rate), with overall half-lives of 11.7 d and 2.1 d, respectively. Prolonged PT and RVVT occurred in 10% of the exposed owls with liver DPN concentrations of 0.122 µg/g and 0.282 µg/g and in 90% of the owls with liver concentrations of 0.638 µg/g and 0.361 µg/g. These liver residue levels associated with coagulopathy fall in the range of values reported in raptor mortality incidents involving DPN. These tissue-based toxicity reference values for coagulopathy in adult screech-owls have application for interpreting nontarget mortality and assessing the hazard of DPN in rodent-control operations. Diphacinone exposure evokes toxicity in raptors within a matter of days; but once exposure is terminated, recovery of hemostasis occurs rapidly

Toxicokinetics and coagulopathy threshold of the rodenticide diphacinone in eastern screech-owls (Megascops asio).

PubMed

Rattner, Barnett A; Horak, Katherine E; Lazarus, Rebecca S; Goldade, David A; Johnston, John J

2014-01-01

In the United States, new regulations on second-generation anticoagulant rodenticides will likely be offset by expanded use of first-generation anticoagulant rodenticides. In the present study, eastern screech-owls (Megascops asio) were fed 10 µg diphacinone/g wet weight food for 7 d, and recovery was monitored over a 21-d postexposure period. By day 3 of exposure, diphacinone (DPN) was detected in liver (1.63 µg/g wet wt) and kidney (5.83 µg/g) and coagulopathy was apparent. By day 7, prothrombin time (PT) and Russell's viper venom time (RVVT) were prolonged, and some individuals were anemic. Upon termination of exposure, coagulopathy and anemia were resolved within 4 d, and residues decreased to <0.3 µg/g by day 7. Liver and kidney DPN elimination occurred in 2 phases (initial rapid loss, followed by slower loss rate), with overall half-lives of 11.7 d and 2.1 d, respectively. Prolonged PT and RVVT occurred in 10% of the exposed owls with liver DPN concentrations of 0.122 µg/g and 0.282 µg/g and in 90% of the owls with liver concentrations of 0.638 µg/g and 0.361 µg/g. These liver residue levels associated with coagulopathy fall in the range of values reported in raptor mortality incidents involving DPN. These tissue-based toxicity reference values for coagulopathy in adult screech-owls have application for interpreting nontarget mortality and assessing the hazard of DPN in rodent-control operations. Diphacinone exposure evokes toxicity in raptors within a matter of days; but once exposure is terminated, recovery of hemostasis occurs rapidly. © 2013 SETAC. This article is a US Government work and is in the public domain in the USA.

Investigations of anticoagulant rodenticide exposure in wildlife in a national park in southern California: distribution, extent, and effects of exposure in multiple carnivores, surveys of human use, and exposure in small mammals and lagomorphs

EPA Science Inventory

Since 1996, we have been studying the ecology and conservation of mammalian carnivores, including bobcats, coyotes, and more recently mountain lions, at Santa Monica Mountains National Recreation Area north of Los Angeles. Although it was not a goal of the study, from the beginn...

Chlorophacinone residues in mammalian prey at a black-tailed prairie dog colony

USGS Publications Warehouse

Vyas, Nimish B.; Hulse, Craig S.; Rice, Clifford P.

2012-01-01

Black-tailed prairie dogs (BTPDs), Cynomys ludovicianus, are an important prey for raptors; therefore, the use of the rodenticide Rozol (0.005% chlorophacinone active ingredient) to control BTPDs raises concern for secondary poisonings resulting from the consumption of contaminated prey by raptors. In the present study, the authors observed Rozol exposure and adverse effects to mammalian prey on 11 of 12 search days of the study. Mammalian hepatic chlorophacinone residues ranged from 0.44 to 7.56 µg/g. Poisoned prey availability was greater than previously reported.

Predictors of pesticide poisoning.

PubMed

Ferguson, J A; Sellar, C; McGuigan, M A

1991-01-01

The analysis of 1,026 reports of suspected pesticide poisonings to the regional Poison Control Centre at the Hospital for Sick Children, Toronto consisted of 597 (58.2%) cases less than six years of age. Age was the strongest predictor: there was a risk of 3.1 that young children would encounter rodenticide poisoning compared to that of insecticides; a ten-fold risk of having symptoms from pesticide poisoning if the victim was over five years of age; an increased risk of 5.9 of exposure to moderate or large amounts of pesticide, compared to small quantities, for those over five years of age; and there was less treatment referral for young children, and a 5.7 risk of being referred if the victim was over the age of five years. Other significant predictor variables include the type of person making the inquiry (lay or physician/nurse), the calendar season of the event, and the location (metropolitan or nonmetropolitan) of the event.

Increased rodenticide exposure rate and risk of toxicosis in barn owls (Tyto alba) from southwestern Canada and linkage with demographic but not genetic factors.

PubMed

Huang, Andrew C; Elliott, John E; Hindmarch, Sofi; Lee, Sandi L; Maisonneuve, France; Bowes, Victoria; Cheng, Kimberly M; Martin, Kathy

2016-08-01

Among many anthropogenic drivers of population decline, continual rapid urbanization and industrialization pose major challenges for the survival of wildlife species. Barn owls (Tyto alba) in southwestern British Columbia (BC) face a multitude of threats ranging from habitat fragmentation to vehicle strikes. They are also at risk from secondary poisoning of second-generation anticoagulant rodenticides (SGARs), a suite of toxic compounds which at high doses results in a depletion of blood clotting factors leading to internal bleeding and death. Here, using long-term data (N = 119) for the hepatic residue levels of SGAR, we assessed the risk of toxicosis from SGAR for the BC barn owl population over the past two decades. We also investigated whether sensitivity to SGAR is associated with genetic factors, namely Single Nucleotide Polymorphisms (SNPs) found in the CYP2C45 gene of barn owls. We found that residue concentration for total SGAR was significantly higher in 2006-2013 (141 ng/g) relative to 1992-2003 (57 ng/g). The proportion of owls exposed to multiple SGAR types was also significantly higher in 2006-2013. Those measures accordingly translate directly into an increase in toxicosis risk level. We also detected demographic differences, where adult females showed on average lower concentration of total SGAR (64 ng/g) when compared to adult males (106 ng/g). Juveniles were overall more likely to show signs of toxicosis than adults (33.3 and 6.9 %, respectively), and those symptoms were positively predicted by SGAR concentrations. We found no evidence that SNPs in the CYP2C45 gene of barn owls were associated with intraspecific variation in SGAR sensitivity. We recommend several preventative measures be taken to minimize wildlife exposure to SGAR.

Poisoning deaths in Central China (Hubei): A 10-year retrospective study of forensic autopsy cases.

PubMed

Zhou, Lan; Liu, Liang; Chang, Lin; Li, Ling

2011-01-01

A retrospective study of autopsy cases was conducted at the Department of Forensic Medicine, Tongji Medical College (DFM-TMC), in Hubei, China to describe the characteristics of poisoning deaths from 1999 to 2008. A total of 212 poisoning deaths were investigated by DFM-TMC during the 10-year period. The poisoning deaths ranged from 17 cases in 1999 to 27 cases in 2008. Of the 212 cases, 82 deaths (38.7%) were from pesticides, 36 deaths (17.0%) from carbon monoxide, 34 deaths (16.0%) from drugs, 22 deaths (10.4%) from alcohol, 17 deaths (8.0%) from other chemicals, 15 deaths (7.1%) from poisonous plants and animals, and six deaths (2.8%) from heavy metals. Of the 82 pesticide poisoning deaths, 43 (52.4%) cases were caused by rodenticides, mainly tetramine (N = 39). The majority of poisoning deaths were accidents (63.7%), followed by suicides (25.9%) and homicides (3.8%). The manner of death could not be determined in 14 cases (6.6%). © 2010 American Academy of Forensic Sciences.

Agricultural and horticultural chemical poisonings: mortality and morbidity in the United States.

PubMed

Klein-Schwartz, W; Smith, G S

1997-02-01

To provide a comprehensive analysis of morbidity and mortality from poisoning by agricultural and horticultural chemicals in the United States. Descriptive analysis of national mortality data, National Hospital Discharge Survey data, and American Association of Poison Control Centers national data for 1985 through 1990. There were 341 fatalities from agricultural and horticultural chemicals over the 6-year period, of which 64% were suicides, 28% were unintentional, and 8% were of undetermined intent. There were 25,418 hospitalizations; 78% were reported to be unintentional. Both deaths and hospitalizations occurred more frequently in males, and rates were higher in nonwhites than in whites. There were 338,170 poison exposures reported to poison centers for fungicides, herbicides, pesticides/insecticides, and rodenticides. Life-threatening manifestations or long-term sequelae occurred in 782 cases, and 97 deaths were reported. Pesticides and insecticides accounted for 72% of the poison center cases and 63% of the fatalities. Although they accounted for only 8% of poison exposures, herbicide deaths were disproportionately high (25%). Poisonings with agricultural and horticultural chemicals are an important public health problem. Prevention efforts need to incorporate the fact that many serious cases, such as paraquat poisonings, are suicidal in nature.

An in-vitro–in-vivo model for the transdermal delivery of cholecalciferol for the purposes of rodent management

PubMed Central

Davies, J.; Ingham, A.

2015-01-01

The natural selection of anticoagulant resistant rats has resulted in a need for an alternative to anticoagulant rodenticides which differs in both active ingredient and in the method of dosing. Cholecalciferol toxicity to rodents using the dermal route is demonstrated using a variety of penetration enhancing formulations in two in-vitro models and finally in-vivo. A 1 ml dose of 50/50 (v/v) DMSO/ethanol containing 15% (v/v) PEG 200 and 20% (w/v) cholecalciferol was judged as ‘sufficiently effective’ in line with the European Union’s Biocidal Products Regulation (No. 528/2012) during in-vivo studies. This dose was found to cause 100% mortality in a rat population in 64.4 h (±22 h). PMID:25835266

An in-vitro-in-vivo model for the transdermal delivery of cholecalciferol for the purposes of rodent management.

PubMed

Davies, J; Ingham, A

2015-06-20

The natural selection of anticoagulant resistant rats has resulted in a need for an alternative to anticoagulant rodenticides which differs in both active ingredient and in the method of dosing. Cholecalciferol toxicity to rodents using the dermal route is demonstrated using a variety of penetration enhancing formulations in two in-vitro models and finally in-vivo. A 1 ml dose of 50/50 (v/v) DMSO/ethanol containing 15% (v/v) PEG 200 and 20% (w/v) cholecalciferol was judged as 'sufficiently effective' in line with the European Union's Biocidal Products Regulation (No. 528/2012) during in-vivo studies. This dose was found to cause 100% mortality in a rat population in 64.4h (± 22h). Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of pelletized anticoagulant rodenticides on California quail

USGS Publications Warehouse

Blus, L.J.; Henny, C.J.; Grove, R.A.

1985-01-01

A moribund, emaciated California quail (Callipepla californica) that was found in an orchard in the state of Washington had an impacted crop and gizzard. Pellets containing the anticoagulant chlorophacinone (Rozol, RO) were in the crop; the gizzard contents consisted of a pink mass of paraffin that was selectively accumulated from the paraffinized pellets. The plasma prothrombin time of 28 sec was near that determined for control quail. The signs of RO intoxication seen in the moribund wild quail were duplicated in captive quail given ad libitum diets of either RO or another paraffinized chlorophacinone pellet (Mr. Rat Guard II, MRG). This left little doubt that paraffin impaction of the gizzard was the primary problem. All captive quail fed RO or MRG pellets showed no increases in prothrombin times compared to control values, died in an emaciated condition, and had gizzards impacted with paraffin.

Program for Army Spill Sites. Phase 1, Task 24, Version 3.2. Volume 1

DTIC Science & Technology

1987-11-01

7355 14 gals Diazinon 6840-00-753-5038 197 lbs Vapona 140 strips Naled 6840-00-926-9163 22 gals Carbaryl 100 lbs Propoxur 1 gal Baygon Propoxur 6840...544 thiram 75% Arsenate of Lead 2 lbs Building 544 Baygon Roach Bait 2.5 lbs Building 544 propoxur 2% Cyanogas-A 1 lb Building 544 Calcium Cyanide 42...Rodenticidal Bait 150 lbs Building 544 Anticoagulant warfarin 0.025% 6840-00-753-4973 Sevin Sprayable 220 lbs Building 544 Carbaryl 80% 6840-00-932-7297

A population model of the impact of a rodenticide containing strychnine on Great Basin Gophersnakes (Pituophis catenifer deserticola).

PubMed

Bishop, Christine A; Williams, Kathleen E; Kirk, David A; Nantel, Patrick; Reed, Eric; Elliott, John E

2016-09-01

Strychnine is a neurotoxin and an active ingredient in some rodenticides which are placed in burrows to suppress pocket gopher (Thomomys talpoides) populations in range and crop land in western North America. The population level impact was modelled of the use of strychnine-based rodenticides on a non-target snake species, the Great Basin Gophersnake (Pituophis catenifer deserticola), which is a predator of pocket gopher and a Species at Risk in Canada. Using information on population density, demographics, and movement and habitat suitability for the Gophersnake living in an agricultural valley in BC, Canada, we estimated the impact of the poisoning of adult snakes on the long-term population size. To determine the area where Gophersnakes could be exposed to strychnine, we used vendor records of a rodenticide, and quantified the landcover areas of orchards and vineyards where the compound was most commonly applied. GIS analysis determined the areas of overlap between those agricultural lands and suitable habitats used by Gophersnakes. Stage-based population matrix models revealed that in a low density (0.1/ha) population scenario, a diet of one pocket gopher per year wherein 10 % of them carried enough strychnine to kill an adult snake could cause the loss of 2 females annually from the population and this would reduce the population by 35.3 % in 25 years. Under the same dietary exposure, up to 35 females could die per year in a high density (0.4/ha) population which would result in a loss of 50 % of adults in 25 years.

Anticoagulant rodenticides in urban bobcats: exposure, risk factors and potential effects based on a 16-year study

USGS Publications Warehouse

Serieys, Laurel E.K.; Armenta, Tiffany C.; Moriarty, Joanne G.; Boydston, Erin E.; Lyren, Lisa M.; Poppenga, Robert H.; Crooks, Kevin R.; Wayne, Robert K.; Riley, Seth P. D.

2015-01-01

Anticoagulant rodenticides (ARs) are increasingly recognized as a threat to nontarget wildlife. High exposure to ARs has been documented globally in nontarget predatory species and linked to the high prevalence of an ectoparasitic disease, notoedric mange. In southern California, mange associated with AR exposure has been the proximate cause of a bobcat (Lynx rufus) population decline. We measured AR exposure in bobcats from two areas in southern California, examining seasonal, demographic and spatial risk factors across landscapes including natural and urbanized areas. The long-term study included bobcats sampled over a 16-year period (1997–2012) and a wide geographic area. We sampled blood (N = 206) and liver (N = 172) to examine exposure ante- and post-mortem. We detected high exposure prevalence (89 %, liver; 39 %, blood) and for individuals with paired liver and blood data (N = 64), 92 % were exposed. Moreover, the animals with the most complete sampling were exposed most frequently to three or more compounds. Toxicant exposure was associated with commercial, residential, and agricultural development. Bobcats of both sexes and age classes were found to be at high risk of exposure, and we documented fetal transfer of multiple ARs. We found a strong association between certain levels of exposure (ppm), and between multiple AR exposure events, and notoedric mange. AR exposure was prevalent throughout both regions sampled and throughout the 16-year time period in the long-term study. ARs pose a substantial threat to bobcats, and likely other mammalian and avian predators, living at the urban-wildland interface.

A negative association between bromadiolone exposure and nestling body condition in common kestrels: management implications for vole outbreaks.

PubMed

Martínez-Padilla, Jesús; López-Idiáquez, David; López-Perea, Jhon J; Mateo, Rafael; Paz, Alfonso; Viñuela, Javier

2017-02-01

Vole outbreaks have been extensively described, along with their impacts on humans, particularly in agricultural areas. The use of rodenticides is a common legal practice to minimise crop damage induced by high vole density for biocidal use. However, rodenticides can have negative direct and indirect impacts on non-target species that feed on voles. We studied whether the use of a second-generation anticoagulant rodenticide (SGAR), bromadiolone, can be detected in the blood of fledglings of wild common kestrels Falco tinnunculus in two areas of central Spain, exploring its possible indirect effects. We found that 16.9% of fledglings had a detectable concentration of bromadiolone in their blood, with an average concentration of 0.248 ± 0.023 ng mL -1 . Fledglings with bromadiolone in their blood, regardless of the concentration, had 6.7% lower body mass than those without detectable bromadiolone. The use of bromadiolone was detectable in the blood of alive non-target species. Detected bromadiolone in blood may reduce the body condition of nestlings, potentially reducing their fitness. The source of bromadiolone found in nestlings needs to be determined in future studies to derive accurate management advice. However, we urge the discontinuation of official SGAR distribution to farmers and their use in agrarian lands to minimise damage of voles on crops, particularly where common kestrels breed, and encourage the use of alternative effective practices. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Sodium fluoroacetate poisoning.

PubMed

Proudfoot, Alex T; Bradberry, Sally M; Vale, J Allister

2006-01-01

Sodium fluoroacetate was introduced as a rodenticide in the US in 1946. However, its considerable efficacy against target species is offset by comparable toxicity to other mammals and, to a lesser extent, birds and its use as a general rodenticide was therefore severely curtailed by 1990. Currently, sodium fluoroacetate is licensed in the US for use against coyotes, which prey on sheep and goats, and in Australia and New Zealand to kill unwanted introduced species. The extreme toxicity of fluoroacetate to mammals and insects stems from its similarity to acetate, which has a pivotal role in cellular metabolism. Fluoroacetate combines with coenzyme A (CoA-SH) to form fluoroacetyl CoA, which can substitute for acetyl CoA in the tricarboxylic acid cycle and reacts with citrate synthase to produce fluorocitrate, a metabolite of which then binds very tightly to aconitase, thereby halting the cycle. Many of the features of fluoroacetate poisoning are, therefore, largely direct and indirect consequences of impaired oxidative metabolism. Energy production is reduced and intermediates of the tricarboxylic acid cycle subsequent to citrate are depleted. Among these is oxoglutarate, a precursor of glutamate, which is not only an excitatory neurotransmitter in the CNS but is also required for efficient removal of ammonia via the urea cycle. Increased ammonia concentrations may contribute to the incidence of seizures. Glutamate is also required for glutamine synthesis and glutamine depletion has been observed in the brain of fluoroacetate-poisoned rodents. Reduced cellular oxidative metabolism contributes to a lactic acidosis. Inability to oxidise fatty acids via the tricarboxylic acid cycle leads to ketone body accumulation and worsening acidosis. Adenosine triphosphate (ATP) depletion results in inhibition of high energy-consuming reactions such as gluconeogenesis. Fluoroacetate poisoning is associated with citrate accumulation in several tissues, including the brain. Fluoride liberated from fluoroacetate, citrate and fluorocitrate are calcium chelators and there are both animal and clinical data to support hypocalcaemia as a mechanism of fluoroacetate toxicity. However, the available evidence suggests the fluoride component does not contribute. Acute poisoning with sodium fluoroacetate is uncommon. Ingestion is the major route by which poisoning occurs. Nausea, vomiting and abdominal pain are common within 1 hour of ingestion. Sweating, apprehension, confusion and agitation follow. Both supraventricular and ventricular arrhythmias have been reported and nonspecific ST- and T-wave changes are common, the QTc may be prolonged and hypotension may develop. Seizures are the main neurological feature. Coma may persist for several days. Although several possible antidotes have been investigated, they are of unproven value in humans. The immediate, and probably only, management of fluoroacetate poisoning is therefore supportive, including the correction of hypocalcaemia.

Acute toxicity, histopathology, and coagulopathy in American kestrels (Falco sparverius) following administration of the rodenticie diphacinone

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Day, Daniel D.; Meteyer, Carol U.; Voler, Steven F.; Eisemann, John D.; Johnston, John J.

2011-01-01

The acute oral toxicity of the anticoagulant rodenticide diphacinone was found to be over 20 times greater in American kestrels (Falco sparverius; median lethal dose 96.8 mg/kg body weight) compared with Northern bobwhite (Colinus virginianus) and mallards (Anas platyrhynchos). Modest evidence of internal bleeding was observed at necropsy, although histological examination of heart, liver, kidney, lung, intestine, and skeletal muscle revealed hemorrhage over a wide range of doses (35.1-675 mg/kg). Residue analysis suggests that the half-life of diphacinone in the liver of kestrels that survived was relatively short, with the majority of the dose cleared within 7 d of exposure. Several precise and sensitive clotting assays (prothrombin time, Russell's viper venom time, thrombin clotting time) were adapted for use in this species, and oral administration of diphacinone at 50 mg/kg increased prothrombin time and Russell?s viper venom time at 48 and 96 h postdose compared with controls. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and generally corresponded with the onset of overt signs of toxicity and lethality. In view of the toxicity and risk evaluation data derived from American kestrels, the involvement of diphacinone in some raptor mortality events, and the paucity of threshold effects data following short-term dietary exposure for birds of prey, additional feeding trials with captive raptors are warranted to characterize more fully the risk of secondary poisoning.

Investigation of Characteristics and Predictive Factors Affecting Mortality from Aluminum Phosphide Poisoning, Iran.

PubMed

Navabi, Seyed Mohammad Navabi; Navabi, Seyed Jafar; Aghaei, Abbas; Shaahmadi, Zahra; Heydari, Ruhollah

2018-05-27

Aluminum phosphide (ALP) or rice tablet is one of the most effective rodenticides used for the protection of grain storages from animals and rodents. ALP poisoning annually leads to mortality in human beings. The aim of this study was to evaluate the characteristics and predictive factors affecting mortality from ALP poisoning. This study evaluated patients with ALP poisoning referred to Imam Khomeini hospital in Kermanshah from 2014 to 2015. There are several data gathered from patient such as age, sex, number of consumed tablets, the number of attempts to commit suicide, elapsed time from consuming till treatment, blood pressure, PH, HCO3 and PCO2. Survivors (recovery) and non-survivors (death) from ALP poisoning are also evaluated in this study. Univariate logistic regression and multivariate analysis have been applied for data analysis. In this study, 48 patients were male and 29 patients were female, respectively (total 77 patient). The average age of survivors and non-survivors were 28.69 and 31.34 years, respectively. All cases (100%) of ALP poisoning were tried to commit suicide. The results showed that the main predictive variables of mortality from ALP poisoning were blood pressure, PH and elapsed time from consuming till treatment. The prognosis of death for patients with ALP poisoning can be determined by awareness of some of the main characteristics or factors such as blood pressure, PH and elapsed time from consuming till treatment. This can give a possibility for healthcare groups to consider more measures in patients with ALP poisoning.

Acute Methanol Poisoning: Prevalence and Predisposing Factors of Haemorrhagic and Non-Haemorrhagic Brain Lesions.

PubMed

Zakharov, Sergey; Kotikova, Katerina; Vaneckova, Manuela; Seidl, Zdenek; Nurieva, Olga; Navratil, Tomas; Caganova, Blazena; Pelclova, Daniela

2016-08-01

The purpose was to study the prevalence and predisposing factors of brain lesions in survivors of acute methanol poisoning. Clinical data on 106 patients with methanol poisoning were collected during the Czech mass poisoning outbreak. Of 83 survivors, in 46 (55%) patients, follow-up examinations including magnetic resonance imaging of brain (MR) were performed 3-8 and 24-28 months after discharge from the hospital. Of 46 patients with a median age of 49 (interquartile range, 35-57) years, 24 (52%) patients had a total of 40 abnormal brain findings with haemorrhagic lesions detected in 15 (33%) and non-haemorrhagic lesions found in 9 (19%) patients. The patients with haemorrhagic brain lesions were more acidemic (lower arterial blood pH, higher base deficit) and had higher glycaemia and lactacidaemia on admission than those without haemorrhages (all p < 0.05). Thirteen of 32 (41%) of patients with systemic anticoagulation and 2 of 14 (14%) of patients without it had haemorrhagic lesions (p = 0.080). Bleeding complications during the treatment occurred in 4 of 15 (27%) patients, and 5 of 15 (33%) patients had conditions predisposing to haemorrhage in the group with haemorrhagic lesions. In three cases with a series of computer tomography (CT)/MR performed during hospitalization, the necrotic lesions in the brain remained non-haemorrhagic during hospitalization and haemorrhagic lesions were detected on the follow-up MR examinations only. No association between brain haemorrhages and systemic anticoagulation during dialysis was found: brain haemorrhages might occur in severely poisoned patients treated without systemic anticoagulation, whereas treatment with high doses of heparin might not lead to brain haemorrhages. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

The epidemiology of childhood poisonings in Cyprus.

PubMed

Koliou, Maria; Ioannou, Chrystalla; Andreou, Kyriaki; Petridou, Alexandra; Soteriades, Elpidoforos Soterakis

2010-07-01

Information on childhood poisonings in Cyprus is limited. Our objective was to examine the epidemiology of poisonings among children in Cyprus. All children up to 15 years of age admitted for poisoning to the Archbishop Makarios Hospital in Nicosia, Cyprus between 2005 and 2008 were included in our study. All hospital poisoning records were reviewed. A total of 257 children were admitted for poisoning. The mean age of children was 3.1 years, of which 83.7% were below the age of 5 years old, while 53% were boys. The poisoning hospitalizations accounted for about 3% of all admissions to the pediatric department during the study period (4 years). The annual cumulative incidence of childhood poisoning hospitalizations was 116 per 100,000 children. Medications accounted for 46.1% of all poisonings, the most frequent cause being paracetamol (9.8%), cardiovascular medications (5.3%), antitussive medications (4.5%), and other painkillers (4.1%). Another 37.6% of hospitalizations involved household products such as household cleaning products (11.8%), petroleum products (11.0%), and rodenticides (5.7%). Among children who ingested petroleum distillates, 55.6% developed clinical symptomatology. The vast majority of cases were accidental (93.8%). Suicidal cases involved children 8-14 years old, mainly girls, and the most frequent poisoning ingested was paracetamol (46.7%). Poisoning hospitalizations represent an important cause of morbidity among children in Cyprus. Preventive strategies should include the education of caregivers on the handling of medications and household products as well as legislation requiring child-resistant packaging for all medications and household products including petroleum distillates.

Serum chemistry, hematologic, and post-mortem findings in free-ranging bobcats (Lynx rufus) with notoedric mange

USGS Publications Warehouse

Serieys, Laurel E.K.; Foley, Janet; Owens, Sean; Woods, Leslie; Boydston, Erin E.; Lyren, Lisa M.; Poppenga, Robert H.; Clifford, Deana L.; Stephenson, Nicole; Rudd, Jaime; Riley, Seth P.D.

2013-01-01

Notoedric mange was responsible for a population decline of bobcats (Lynx rufus) in 2 Southern California counties from 2002–2006 and is now reported to affect bobcats in Northern and Southern California. With this study we document clinical laboratory and necropsy findings for bobcats with mange. Bobcats in this study included free-ranging bobcats with mange (n = 34), a control group of free-ranging bobcats without mange (n = 11), and a captive control group of bobcats without mange (n = 19). We used 2 control groups to evaluate potential anomalies due to capture stress or diet. Free-ranging healthy and mange-infected bobcats were trapped or salvaged. Animals were tested by serum biochemistry, complete blood count, urine protein and creatinine, body weight, necropsy, and assessment for anticoagulant rodenticide residues in liver tissue. Bobcats with severe mange were emaciated, dehydrated, and anemic with low serum creatinine, hyperphosphatemia, hypoglycemia, hypernatremia, and hyperchloremia, and sometimes septicemic when compared to control groups. Liver enzymes and leukocyte counts were elevated in free-ranging, recently captured bobcats whether or not they were infested with mange, suggesting capture stress. Bobcats with mange had lower levels of serum cholesterol, albumin, globulin, and total protein due to protein loss likely secondary to severe dermatopathy. Renal insufficiency was unlikely in most cases, as urine protein:creatinine ratios were within normal limits. A primary gastrointestinal loss of protein or blood was possible in a few cases, as evidenced by elevated blood urea nitrogen, anemia, intestinal parasitism, colitis, gastric hemorrhage, and melena. The prevalence of exposure to anticoagulant rodenticides was 100% (n = 15) in bobcats with mange. These findings paint a picture of debilitating, multisystemic disease with infectious and toxic contributing factors that can progress to death in individuals and potential decline in populations.

Rate of exposure of a sentinel species, invasive American mink (Neovison vison) in Scotland, to anticoagulant rodenticides.

PubMed

Ruiz-Suárez, Norberto; Melero, Yolanda; Giela, Anna; Henríquez-Hernández, Luis A; Sharp, Elizabeth; Boada, Luis D; Taylor, Michael J; Camacho, María; Lambin, Xavier; Luzardo, Octavio P; Hartley, Gill

2016-11-01

Anticoagulant rodenticides (ARs) are highly toxic compounds that are exclusively used for the control of rodent pests. Despite their defined use, they are nonetheless found in a large number of non-target species indicating widespread penetration of wildlife. Attempts to quantify the scale of problem are complicated by non-random sampling of individuals tested for AR contamination. The American mink (Neovison vison) is a wide ranging, non-native, generalist predator that is subject to wide scale control efforts in the UK. Exposure to eight ARs was determined in 99 mink trapped in NE Scotland, most of which were of known age. A high percentage (79%) of the animals had detectable residues of at least one AR, and more than 50% of the positive animals had two or more ARs. The most frequently detected compound was bromadiolone (75% of all animals tested), followed by difenacoum (53% of all mink), coumatetralyl (22%) and brodifacoum (9%). The probability of mink exposure to ARs increased by 4.5% per month of life, and was 1.7 times higher for mink caught in areas with a high, as opposed to a low, density of farms. The number of AR compounds acquired also increased with age and with farm density. No evidence was found for sexual differences in the concentration and number of ARs. The wide niche and dietary overlap of mink with several native carnivore species, and the fact that American mink are culled for conservation throughout Europe, suggest that this species may act as a sentinel species, and the application of these data to other native carnivores is discussed. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

VKORC1 and VKORC1L1 have distinctly different oral anticoagulant dose-response characteristics and binding sites

PubMed Central

Czogalla, Katrin J.; Liphardt, Kerstin; Höning, Klara; Hornung, Veit; Biswas, Arijit; Watzka, Matthias

2018-01-01

Vitamin K reduction is catalyzed by 2 enzymes in vitro: the vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) and its isozyme VKORC1-like1 (VKORC1L1). In vivo, VKORC1 reduces vitamin K to sustain γ-carboxylation of vitamin K-dependent proteins, including coagulation factors. Inhibition of VKORC1 by oral anticoagulants (OACs) is clinically used in therapy and in prevention of thrombosis. However, OACs also inhibit VKORC1L1, which was previously shown to play a role in intracellular redox homeostasis in vitro. Here, we report data for the first time on specific inhibition of both VKOR enzymes for various OACs and rodenticides examined in a cell-based assay. Effects on endogenous VKORC1 and VKORC1L1 were independently investigated in genetically engineered HEK 293T cells that were knocked out for the respective genes by CRISPR/Cas9 technology. In general, dose-responses for 4-hydroxycoumarins and 1,3-indandiones were enzyme-dependent, with lower susceptibility for VKORC1L1 compared with VKORC1. In contrast, rodenticides exhibited nearly identical dose-responses for both enzymes. To explain the distinct inhibition pattern, we performed in silico modeling suggesting different warfarin binding sites for VKORC1 and VKORC1L1. We identified arginine residues at positions 38, 42, and 68 in the endoplasmatic reticulum luminal loop of VKORC1L1 responsible for charge-stabilized warfarin binding, resulting in a binding pocket that is diametrically opposite to that of VKORC1. In conclusion, our findings provide insight into structural and molecular drug binding on VKORC1, and especially on VKORC1L1. PMID:29581108

Development of dietary-based toxic reference values to assess the risk of chlorophacinone to non-target raptorial birds

USGS Publications Warehouse

Rattner, Barnett A.; Lazarus, Rebecca S.; Shultz, S. L.; Horak, Katherine E.; Abbo, Benjamin G.; Volker, Steven F.; Timms, R. M.; O'Brien, J. M.

2014-01-01

Regulatory changes in the use of some second-generation anticoagulant rodenticides in parts of North America may result in expanded use of first-generation anticoagulant rodenticides (FGARs). Recent toxicological studies with captive raptors have demonstrated that these species are considerably more sensitive to the FGAR diphacinone than traditional avian wildlife test species (mallard, bobwhite). We have now examined the toxicity of the FGAR chlorophacinone (CPN) to American kestrels fed rat tissue mechanically-amended with CPN, or rat tissue containing biologically-incorporated CPN, for 7 days. Nominal CPN concentrations in these diets were 0.15, 0.75 and 1.5 µg/g food wet weight, and actual CPN concentration in diets were analytically verified as being close to target values. Food intake was consistent among groups, body weight fluctuated by less than 6%, exposure and adverse effects were generally dose-dependent, and there were no dramatic differences in toxicity between mechanically-amended and biologically-incorporated CPN diets. Using benchmark dose statistical methods, toxic reference values at which clotting times were prolonged in 50% of the kestrels was estimated to be about 80 µg CPN consumed/kg body weight-day for prothrombin time and 40 µg CPN/kg body weight-day for Russell's viper venom time. Based upon carcass CPN residues reported in rodents from field baiting studies, empirical measures of food consumption in kestrels, and dietary-based toxic reference values derived from the 7-day exposure scenario, some free-ranging raptors consuming CPN exposed prey might exhibit coagulopathy and hemorrhage. These sublethal responses associated with exposure to environmentally realistic concentrations of CPN could compromise survival of exposed birds.

[Case report. Phenprocoumon (Marcumar, Falithrom) as an unusual reason for coumarin poisoning in a dog].

PubMed

Lutze, G; Römhild, W; Elwert, J; Leppelt, J; Kutschmann, K

2003-01-01

Coumarin poisoning in dogs is not unusual and is in most cases caused by warfarin, a coumarin derivative which is used as a rodenticide. Competitive inhibition of vitamin K with an incomplete synthesis of the coagulation factors II, VII, IX and X can lead to a significant bleeding tendency. We observed a 3-year old male West Highland White Terrier with a reduced general condition and dyspnoea together with a massive haemothorax. Administration of vitamin K1 (3 mg/kg) led to a rapid improvement of the condition. Coagulation analysis revealed a prolonged activated recalcification time (ARCT), prothrombin time (PT) and aPTT with uncharacteristic thrombin time (TT); factor II, VII and X activities were reduced while factor V activity was normal, all of which are characteristic for coumarin poisoning. HPLC did not reveal the presence of warfarin but of phenoprocoumon, a drug used for thromboembolic prophylaxis in humans. This observation has not been described for dogs to date.

Occupational phosphine gas poisoning at veterinary hospitals from dogs that ingested zinc phosphide--Michigan, Iowa, and Washington, 2006-2011.

PubMed

2012-04-27

Zinc phosphide (Zn3P2) is a readily available rodenticide that, on contact with stomach acid and water, produces phosphine (PH3), a highly toxic gas. Household pets that ingest Zn3P2 often will regurgitate, releasing PH3 into the air. Veterinary hospital staff members treating such animals can be poisoned from PH3 exposure. During 2006-2011, CDC's National Institute for Occupational Safety and Health (NIOSH) received reports of PH3 poisonings at four different veterinary hospitals: two in Michigan, one in Iowa, and one in Washington. Each of the four veterinary hospitals had treated a dog that ingested Zn3P2. Among hospital workers, eight poisoning victims were identified, all of whom experienced transient symptoms related to PH3 inhalation. All four dogs recovered fully. Exposure of veterinary staff members to PH3 can be minimized by following phosphine product precautions developed by the American Veterinary Medical Association (AVMA). Exposure of pets, pet owners, and veterinary staff members to PH3 can be minimized by proper storage, handling, and use of Zn3P2 and by using alternative methods for gopher and mole control, such as snap traps.

[Analysis of reports of cases of pesticide poisoning in Jiangsu Province, China, from 2006 to 2013].

PubMed

Yu, Bin; Ding, Bangmei; Shen, Han; Zhu, Baoli; Gao, Qianqian

2015-03-01

To investigate the characteristics of pesticide poisoning in Jiangsu Province, China, and to provide a scientific basis for developing effective intervention measures and prevention strategies. The data from report cards of pesticide poisoning in Jiangsu Province from 2006 to 2013 were arranged using EXCEL tables, and assessed. Statistical analysis was applied to the epidemiological data using SPSS. From 2006 to 2013, a total of 32672 cases of pesticide poisoning were reported in Jiangsu Province. Most of the cases were caused by non-occupational poisoning (life poisoning) (72.78%). A majority of patients with pesticide poisoning were 35-54 years old (40.85%) or older than 65 years (15.69%). There were more female patients (58.22%) than male patients (41.78%). Among patients with occupational poisoning, male patients (50.90%) were more than female patients. Among patients with non-occupational poisoning, female patients were more than male patients (38.37%). Pesticide poisoning mainly occurred from July to September. The case-fatality rate of occupational poisoning (0.47%) was lower than that of non-occupational poisoning (7.10%). All 13 cities in Jiangsu Province reported cases of pesticide poisoning. There were more cases in the northern regions than in the southern regions. Pesticide poisoning was mainly caused by organophosphorus insecticides including methamidophos, dichlorvos, dimethoate, omethoate, and parathion, which accounted for 65.58%of all cases. Paraquat had the highest case-fatality rate (10.06%) among all pesticides, followed by tetramine (10.00%), dimethoate or omethoate (7.85%), methamidophos (7.79%), and dimehypo (7.68%). Pesticide poisoning cannot be ignored. The management and control should be improved in production and usage of highly toxic pesticides including organophosphorus insecticides, rodenticides, and herbicides. More attention should be paid to the protection of vulnerable groups including women, children, and the elderly.

Pesticide poisoning trend analysis of 13 years: a retrospective study based on telephone calls at the National Poisons Information Centre, All India Institute of Medical Sciences, New Delhi.

PubMed

Peshin, Sharda Shah; Srivastava, Amita; Halder, Nabanita; Gupta, Yogendra Kumar

2014-02-01

The study was designed to analyze the incidence and pattern of pesticide poisoning calls reported to the National Poisons Information Centre (NPIC), AIIMS, New Delhi and highlight the common classes of pesticides involved in poisoning. The telephone calls received by the Centre during the thirteen year period (1999-2012) were entered into a preset proforma and then into a retrievable database. A total of 4929 calls of pesticide poisoning were recorded. The data was analyzed with respect to age, gender, mode and type of poisoning. The age ranged from 1 to 65 years with the preponderance of males (M = 62.19%, F = 37.80%). The age group mainly involved in poisoning was 18-35 years. While 59.38% calls pertained to household pesticides, 40.61% calls related to agricultural pesticides. The common mode of poisoning was intentional (64.60%) followed by accidental (34.40%) and unknown (1%). Amongst the household pesticides, the highest number of calls were due to pyrethroids (26.23%) followed by rodenticides (17.06%), organophosphates (6.26%), carbamates (4.95%) and others (4.86%). In agricultural pesticides group, the organophosphates (9.79%) ranked the first followed by, aluminium phosphide (9.65%), organochlorines (9.31%), pyrethroids (3.87%), herbicides, weedicides and fungicides (3.20%), ethylene dibromide (2.82%), and others (1.70%). The data analysis shows a high incidence of poisoning due to household pesticides as compared to agricultural pesticides, clearly emphasizing the need for creating awareness and education about proper use and implementation of prevention programmes. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Deaths from pesticide poisoning in England and Wales: 1945-1989.

PubMed

Casey, P; Vale, J A

1994-02-01

1. Data on deaths from pesticide poisoning occurring in England and Wales between 1945 and 1989 (no data are available for 1954) have been collated; pesticides were responsible for only 1012 (1.1%) of the 87,385 deaths from poisoning (excluding those due to carbon monoxide) occurring over this 44 year period. At least 73% of all pesticide fatalities were due to suicide and overall there was a predominance of males (male:female ratio 2.4:1). No deaths from pesticide poisoning in children under 10 years have been reported since 1974 although almost 50% of suspected pesticide poisoning incidents involve this age group. 2. Herbicides were responsible for 787 (78%) fatal poisonings, 110 (11%) were caused by insecticides, 69 (6.8%) by rodenticides, 30 (3.0%) by wood preservatives and 16 (1.6%) by other pesticides. 3. The herbicide, paraquat, was responsible for 570 of 1012 (56%) deaths and, although there has been a progressive decline in the annual number of deaths from paraquat poisoning since 1982, paraquat remains the most common cause of fatal pesticide poisoning in England and Wales. 4. Sodium chlorate caused 113 (11.2%) deaths, most of these fatalities occurring between 1965 and 1983; only one death has been recorded since 1984. The phenoxyacetate herbicides resulted in 50 deaths; 2,4-D was implicated most commonly. Sixty-eight deaths were due to organophosphorus insecticides; demeton-S-methyl, malathion and mevinphos were involved most frequently. Only eight deaths resulted from organochlorine insecticides and two of these also involved an organophosphorus insecticide.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of an Analytical Procedure for the Determination of Multiclass Compounds for Forensic Veterinary Toxicology.

PubMed

Sell, Bartosz; Sniegocki, Tomasz; Zmudzki, Jan; Posyniak, Andrzej

2018-04-01

Reported here is a new analytical multiclass method based on QuEChERS technique, which has proven to be effective in diagnosing fatal poisoning cases in animals. This method has been developed for the determination of analytes in liver samples comprising rodenticides, carbamate and organophosphorus pesticides, coccidiostats and mycotoxins. The procedure entails addition of acetonitrile and sodium acetate to 2 g of homogenized liver sample. The mixture was shaken intensively and centrifuged for phase separation, which was followed by an organic phase transfer into a tube containing sorbents (PSA and C18) and magnesium sulfate, then it was centrifuged, the supernatant was filtered and analyzed by liquid chromatography tandem mass spectrometry. A validation of the procedure was performed. Repeatability variation coefficients <15% have been achieved for most of the analyzed substances. Analytical conditions allowed for a successful separation of variety of poisons with the typical screening detection limit at ≤10 μg/kg levels. The method was used to investigate more than 100 animals poisoning incidents and proved that is useful to be used in animal forensic toxicology cases.

Pesticide poisoning in Chitwan, Nepal: a descriptive epidemiological study.

PubMed

Gyenwali, Deepak; Vaidya, Abhinav; Tiwari, Sundar; Khatiwada, Prakash; Lamsal, Daya Ram; Giri, Shrikrishana

2017-07-03

Globally, there is a growing concern over pesticides use, which has been linked to self-harm and suicide. However, there is paucity of research on the epidemiology of pesticides poisoning in Nepal. This study is aimed at assessing epidemiological features of pesticides poisoning among hospital-admitted cases in selected hospitals of Chitwan District of Nepal. A hospital-based quantitative study was carried out in four major hospitals of Chitwan District. Information on all pesticides poisoning cases between April 1 and December 31, 2015, was recorded by using a Pesticides Exposure Record (PER) form. A total of 439 acute pesticides poisoning cases from 12 districts including Chitwan and adjoining districts attended the hospitals during the 9-month-long study period. A majority of the poisoned subjects deliberately used pesticides (89.5%) for attempted suicide. The total incidence rate was 62.67/100000 population per year. Higher annual incidence rates were found among young adults (111.66/100000 population), women (77.53/100000 population) and individuals from Dalit ethnic groups (98.22/100000 population). Pesticides responsible for poisoning were mostly insecticides (58.0%) and rodenticides (20.8%). The most used chemicals were organophosphates (37.3%) and pyrethroids (36.7%). Of the total cases, 98.6% were hospitalized, with intensive care required for 41.3%. The case fatality rate among admitted cases was 3.8%. This study has indicated that young adults, females and socially disadvantaged ethnic groups are at a higher risk of pesticides poisoning. Pesticides are mostly misused intentionally as an easy means for committing suicide. It is recommended that the supply of pesticides be properly regulated to prevent easy accessibility and misuse. A population-based study is warranted to reveal the actual problem of pesticides exposure and intoxication in the community.

[The characteristics and trends of acute pesticide poisoning of Shaoxing in 2006 to 2011].

PubMed

Jiang, Guo-qin; Lian, Ling-jun; Wang, Chun-hui; Li, Ming; Wang, Ji-gang; Pan, Nan-yan; Wang, Sha-sha

2013-07-01

To describe the epidemiological characteristics of acute pesticide poisoning in Shaoxing, China during 2006-2011 and to provide a reference for the prevention and control of pesticide poisoning. The data on pesticide poisoning in Shaoxing during 2006-2011 were obtained from the China Information System for Disease Control and Prevention and were then analyzed. A total of 2024 cases of acute pesticide poisoning were reported in Shaoxing during 2006-2011, and 44 cases were missed, accounting for 2.1% (44/2068) of all cases. Among the 2024 cases, 119 (5.9%) died; the fatality rates of productive poisoning and unproductive poisoning were 1.0% (3/289) and 6.7% (116/1735), respectively. The reported cases included 1038 (51.3%) females and 986 (48.7%) males, and there were no significant differences in the ratio between male and female cases of acute pesticide poisoning from 2006 to 2011 (χ2 = 9.16, P = 0.10). The 2024 cases had a mean age of 47.0±18.7 years; the male cases had a significantly higher mean age than the female cases (50.7±19.0 vs 43.4±17.8 years, t = 9.01, P < 0.001). Among the 2024 cases, 289 (14.3%) suffered productive poisoning, and 1735 (85.7%) suffered unproductive poisoning. In the 986 male cases, 219 (22.2%) suffered productive poisoning; in the 1038 female cases, 968 (93.3%) suffered unproductive poisoning. The pesticides that caused poisoning included insecticide (86.7%, 1754/2024), herbicide (5.1%, 104/2024), rodenticide (3.6%, 72/2024), and bactericide, mixed preparation, biochemical pesticides, and other four categories of pesticides (4.6%, 94/2024); of the 1754 cases caused by insecticide, 1455 (83.0%) were attributed to organophosphorus insecticide. The incidence of unproductive acute pesticide poisoning is high in Shaoxing, and it mainly affects females. Most cases of acute pesticide poisoning are aged 30∼60 years. Insecticide is the main cause of poisoning. It is necessary to enhance health knowledge popularization and safety management of pesticides.

Development of a new categorization system for pesticides exposure to support harmonized reporting between EU Member States.

PubMed

Settimi, Laura; Orford, Rob; Davanzo, Franca; Hague, Charlotte; Desel, Herbert; Pelclova, Daniela; Dragelyte, Gabija; Mathieu-Nolf, Monique; Adams, Richard; Duarte-Davidson, Raquel

2016-05-01

European legislation requires reporting from Member States on acute poisoning incidents involving pesticides. However, standard rules for data collection and reporting have not yet been set out. The new categorization system presented in this paper is aimed at enabling Member States to gather comparable data and provide standard reporting on pesticide poisoning exposures. European Regulations providing separate official categorization of biocidal and plant protection pesticides, were used as a basis to build up a unified pesticide categorization and coding system. Data on selected pesticide exposures collected by Poison Control Centres in six EU countries were reviewed, categorized and reported according to the proposed system. The resulting pesticide categorization system has two dimensions. The first part identifies the main category of use, i.e. biocide/plant protection pesticide/unknown, and the secondary category of use, e.g. Rodenticides, Insecticides and acaricides. The second part of the system is organized into two levels: level one identifies chemical grouping, e.g. Coumarins, Pyrethrins/pyrethroids, while level two identifies the active compound by using its Chemical Abstract Service Registry Number. The system was used to provide a unified categorization to compare exposures to plant protection and biocidal Rodenticides and Pyrethrins/pyrethroids Insecticides and acaricides identified by six EU member states. The developed pesticide categorization system was successfully applied to data extracted from different databases and was able to make the required information comparable. The data reported filling in common templates containing a pre-ordinate list of active compounds categorized according the proposed system, highlighted different capabilities in data collection and recording, showing that some of the collaborating centres were not able to distinguish between main categories of pesticide products or provide information on active compounds. The results indicate that a special effort should be dedicated to support detailed data recording at national level. Providing common tools to systematically report to the EU Commission hazardous exposures to pesticides, as well as to other selected categories of products, could allow for data comparability between Member States and greatly improve post marketing surveillance and alerting systems in Europe. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anticoagulant rodenticides and wildlife: Concluding remarks

USGS Publications Warehouse

van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.

2018-01-01

Rodents are known to affect human society globally in various adverse ways, resulting in a widespread demand for their continuous control. Anticoagulant rodenticides (ARs) have been, and currently remain, the cornerstone of rodent control throughout the world. Although alternative control methods exist, they are generally less effective. ARs work by affecting vitamin K metabolism, thereby preventing the activation of blood clotting factors and eventual coagulopathy. Since ARs are non-selective, their undoubted benefits for rodent control have to be balanced against the environmental risks that these compounds pose. Although they have been used for decades, pharmacokinetic and toxicokinetic data are mainly available for laboratory mammals and have concentrated on acute effects. Limited information is available on chronic exposure scenarios and for wildlife species. Important gaps exist in our understanding of the large inter- and intra-species differences in sensitivity to ARs, especially for non-target species, and in our knowledge about the occurrence and importance of sub-lethal effects in wildlife. It is clear that mere presence of AR residues in the body tissues may not indicate the occurrence of effects, although unequivocal assessment of effects under field conditions is difficult. Ante-mortem symptoms, like lethargy, subdued behaviour and unresponsiveness are generally not very specific as is true for more generic post-mortem observations (e.g. pallor of the mucous membranes or occurrence of haemorrhages). It is only by combining ante or post-mortem data with information on exposure that effects in the field may be confirmed. We do know however that a wide variety of non-target species are directly exposed to ARs. Secondary exposure in predators is also widespread although there is limited information on whether this exposure causes actual effects. Exposure is driven by ecological factors and is context specific with respect to spatial habitat configuration and bait placement. Another key factor that affects the interaction between ARs and wildlife is the development of resistance in target species. The development of resistance has resulted in higher use of SGARs, thereby increasing the potential of non-target and secondary exposure. AR use has increasingly become more strictly regulated, increasing the need for alternatives. Alternatives are available, including non-anticoagulant rodenticides, but these may also pose significant risk to environmental organisms, humans and pets. There are also various mitigation measures that can be implemented when using ARs, including bait protection, pulsed baiting at the onset of infestation, restricting use by non-professionals, and avoiding use in areas of high non-target density. Reduction in secondary exposure may result from e.g. non-chemical control, habitat management, and, in agricultural habitats, the use of lure crops and supplemental feeding. Such Integrated Pest Management (IPM) may not only reduce non-target exposure but also benefit resistance management. Barriers to adopt IPM approaches however, include the perception that they do not work or too slowly and are more laborious, expensive and time consuming. It is therefore important that the expectations of stakeholders are considered and managed. Nevertheless, further development of alternatives and IPM measures is essential, so the key research priority related to rodent control may ultimately be to address the lack of scientific assessment of the effectiveness of both specific AR mitigation measures and of IPM approaches to rodent control.

Pesticide-related poison center exposures in children and adolescents aged ≤19 years in Texas, 2000-2013.

PubMed

Trueblood, Amber B; Forrester, Mathias B; Han, Daikwon; Shipp, Eva M; Cizmas, Leslie H

2016-11-01

Although national poison center data show that pesticides were the 8th most commonly reported substance category (3.27%) for children aged ≤5 years in 2014, there is limited information on childhood and adolescent pesticide exposures. This study assessed pesticide-related poison center exposures in children and adolescents aged ≤19 years from 2000-2013 in Texas to characterize the potential burden of pesticides. Pesticide-related poison center exposures among children and adolescents aged ≤19 years reported to Texas poison centers were identified. The distribution of exposures was estimated by gender, age category, medical outcome, management site, exposure route, and pesticide category. From 2000 to 2013, there were 61,147 pesticide-related poison center exposures in children and adolescents aged ≤19 years. The prevalence was highest among males at 864.24 per 100,000 population. The prevalence of unintentional exposures was highest among children aged ≤5 years at 2310.69 per 100,000 population, whereas the prevalence of intentional exposures was highest among adolescents aged 13-19 years at 13.82 per 100,000 population. A majority of medical outcomes reported were classified as having no effect (30.24%) and not followed, but minimal clinical effects possible (42.74%). Of all the exposures, 81.24% were managed on site. However, 57% of intentional exposures were referred to or treated at a health-care facility. The most common routes of exposure were ingestion (80.83%) and dermal (17.21%). The most common pesticide categories included rodenticides (30.02%), pyrethrins/pyrethroids (20.69%), and other and unspecified insecticides (18.14%). The study found differences in the frequency of exposures by intent for sex and age categories, and identified the most common medical outcomes, management site, exposure route, and pesticide category. Through characterizing pesticide-related poison center exposures, future interventions can be designed to address groups with higher prevalence of exposure.

Strychnine overdose following ingestion of gopher bait.

PubMed

Lindsey, Tania; O'Hara, Joseph; Irvine, Rebecca; Kerrigan, Sarah

2004-03-01

A 52-year-old male was discovered supine on his bed in a state of early decomposition. Commercial strychnine-treated gopher pellets were found in the home, and suicide notes were present at the scene. Biological fluids and tissues were tested for basic, acidic, and neutral drugs using gas chromatography-mass spectrometry. Concentrations of strychnine in heart and femoral blood were 0.96 and 0.31 mg/L, respectively. Vitreous fluid, bile, urine, liver, and brain specimens contained 0.36 mg/L, 1.17 mg/L, 2.92 mg/L, 4.59 mg/kg, and 0.86 mg/kg strychnine, respectively. No other drugs were detected in any of the samples. The cause of death was attributed to rodenticide poisoning, and the manner of death was suicide.

Clinical characteristics of zinc phosphide poisoning in Thailand.

PubMed

Trakulsrichai, Satariya; Kosanyawat, Natcha; Atiksawedparit, Pongsakorn; Sriapha, Charuwan; Tongpoo, Achara; Udomsubpayakul, Umaporn; Rittilert, Panee; Wananukul, Winai

2017-01-01

The objectives of this study were to describe the clinical characteristics and outcomes of poisoning by zinc phosphide, a common rodenticide in Thailand, and to evaluate whether these outcomes can be prognosticated by the clinical presentation. A 3-year retrospective cohort study was performed using data from the Ramathibodi Poison Center Toxic Exposure Surveillance System. In total, 455 poisonings were identified. Most were males (60.5%) and from the central region of Thailand (71.0%). The mean age was 39.91±19.15 years. The most common route of exposure was oral (99.3%). Most patients showed normal vital signs, oxygen saturation, and consciousness at the first presentation. The three most common clinical presentations were gastrointestinal (GI; 68.8%), cardiovascular (22.0%), and respiratory (13.8%) signs and symptoms. Most patients had normal blood chemistry laboratory results and chest X-ray findings at presentation. The median hospital stay was 2 days, and the mortality rate was 7%. Approximately 70% of patients underwent GI decontamination, including gastric lavage and a single dose of activated charcoal. In all, 31 patients were intubated and required ventilator support. Inotropic drugs were given to 4.2% of patients. Four moribund patients also received hyperinsulinemia-euglycemia therapy and intravenous hydrocortisone; however, all died. Patients who survived and died showed significant differences in age, duration from taking zinc phosphide to hospital presentation, abnormal vital signs at presentation (tachycardia, low blood pressure, and tachypnea), acidosis, hypernatremia, hyperkalemia, in-hospital acute kidney injury, in-hospital hypoglycemia, endotracheal tube intubation, and inotropic requirement during hospitalization ( P <0.05). Zinc phosphide poisoning causes fatalities. Most patients have mild symptoms, and GI symptoms are the most common. Patients who present with abnormal vital signs or electrolytes might have more severe poisoning and should be closely monitored and aggressively treated. All patients should be observed in the hospital for 2 days and followed up for cardiovascular and respiratory symptoms, electrolyte balances, kidney function, and blood glucose.

Fast targeted analysis of 132 acidic and neutral drugs and poisons in whole blood using LC-MS/MS.

PubMed

Di Rago, Matthew; Saar, Eva; Rodda, Luke N; Turfus, Sophie; Kotsos, Alex; Gerostamoulos, Dimitri; Drummer, Olaf H

2014-10-01

The aim of this study was to develop an LC-MS/MS based screening technique that covers a broad range of acidic and neutral drugs and poisons by combining a small sample volume and efficient extraction technique with simple automated data processing. After protein precipitation of 100μL of whole blood, 132 common acidic and neutral drugs and poisons including non-steroidal anti-inflammatory drugs, barbiturates, anticonvulsants, antidiabetics, muscle relaxants, diuretics and superwarfarin rodenticides (47 quantitated, 85 reported as detected) were separated using a Shimadzu Prominence HPLC system with a C18 separation column (Kinetex XB-C18, 4.6mm×150mm, 5μm), using gradient elution with a mobile phase of 25mM ammonium acetate buffer (pH 7.5)/acetonitrile. The drugs were detected using an ABSciex(®) API 2000 LC-MS/MS system (ESI+ and -, MRM mode, two transitions per analyte). The method was fully validated in accordance with international guidelines. Quantification data obtained using one-point calibration compared favorably to that using multiple calibrants. The presented LC-MS/MS assay has proven to be applicable for determination of the analytes in blood. The fast and reliable extraction method combined with automated processing gives the opportunity for high throughput and fast turnaround times for forensic and clinical toxicology. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Yellow phosphorus-induced Brugada phenocopy.

PubMed

Dharanipradab, Mayakrishnan; Viswanathan, Stalin; Kumar, Gokula Raman; Krishnamurthy, Vijayalatchumy; Stanley, Daphene Divya

Metallic phosphides (of aluminum and phosphide) and yellow phosphorus are commonly used rodenticide compounds in developing countries. Toxicity of yellow phosphorus mostly pertains to the liver, kidney, heart, pancreas and the brain. Cardiotoxicity with associated Brugada ECG pattern has been reported only in poisoning with metallic phosphides. Brugada phenocopy and hepatic dysfunction were observed in a 29-year-old male following yellow phosphorus consumption. He had both type 1 (day1) and type 2 (day2) Brugada patterns in the electrocardiogram, which resolved spontaneously by the third day without hemodynamic compromise. Toxins such as aluminum and zinc phosphide have been reported to induce Brugada ECG patterns due to the generation of phosphine. We report the first case of yellow phosphorus-related Brugada phenocopy, without hemodynamic compromise or malignant arrhythmia. Copyright © 2017 Elsevier Inc. All rights reserved.

48 CFR 1552.235-73 - Access to Federal Insecticide, Fungicide, and Rodenticide Act Confidential Business Information...

Code of Federal Regulations, 2010 CFR

2010-10-01

... Insecticide, Fungicide, and Rodenticide Act Confidential Business Information (APR 1996). 1552.235-73 Section... Insecticide, Fungicide, and Rodenticide Act Confidential Business Information (APR 1996). As prescribed in... Act Confidential Business Information (APR 1996) In order to perform duties under the contract, the...

Pesticide exposure in children.

PubMed

Roberts, James R; Karr, Catherine J

2012-12-01

Pesticides are a collective term for a wide array of chemicals intended to kill unwanted insects, plants, molds, and rodents. Food, water, and treatment in the home, yard, and school are all potential sources of children's exposure. Exposures to pesticides may be overt or subacute, and effects range from acute to chronic toxicity. In 2008, pesticides were the ninth most common substance reported to poison control centers, and approximately 45% of all reports of pesticide poisoning were for children. Organophosphate and carbamate poisoning are perhaps the most widely known acute poisoning syndromes, can be diagnosed by depressed red blood cell cholinesterase levels, and have available antidotal therapy. However, numerous other pesticides that may cause acute toxicity, such as pyrethroid and neonicotinoid insecticides, herbicides, fungicides, and rodenticides, also have specific toxic effects; recognition of these effects may help identify acute exposures. Evidence is increasingly emerging about chronic health implications from both acute and chronic exposure. A growing body of epidemiological evidence demonstrates associations between parental use of pesticides, particularly insecticides, with acute lymphocytic leukemia and brain tumors. Prenatal, household, and occupational exposures (maternal and paternal) appear to be the largest risks. Prospective cohort studies link early-life exposure to organophosphates and organochlorine pesticides (primarily DDT) with adverse effects on neurodevelopment and behavior. Among the findings associated with increased pesticide levels are poorer mental development by using the Bayley index and increased scores on measures assessing pervasive developmental disorder, inattention, and attention-deficit/hyperactivity disorder. Related animal toxicology studies provide supportive biological plausibility for these findings. Additional data suggest that there may also be an association between parental pesticide use and adverse birth outcomes including physical birth defects, low birth weight, and fetal death, although the data are less robust than for cancer and neurodevelopmental effects. Children's exposures to pesticides should be limited as much as possible.

Characteristics of pesticide-related hospitalizations, Louisiana, 1998-2007.

PubMed

Badakhsh, Roshan; Lackovic, Michelle; Ratard, Raoult

2010-01-01

Pesticides are widely used on agricultural crops and in homes, workplaces, and public spaces. Exposure to pesticides can cause acute and chronic health effects. We analyzed data from the Louisiana Hospital Inpatient Discharge Database from 1998 through 2007 to characterize hospitalizations involving pesticides. Data for the study period consisted of 384 pesticide-related hospitalizations. We used demographic information and diagnosis codes for analysis. Males consistently had higher hospitalization rates than females (p=0.0073). Children aged 0-4 years had the highest pesticide-related hospitalization rate of all age groups (2.69 hospitalizations per 100,000); children aged 5-9 years had the lowest rate (0.36 hospitalizations per 100,000). Compared with adults, children had a higher rate of disinfectant exposure (15% vs. 5%; odds ratio [OR] = 3.41, 95% confidence interval [CI] 1.61, 7.21; p=0.0008) and rodenticide exposure (14% vs. 2%; OR=8.55, 95% CI 3.07, 23.78; p<0.0001). Rural parishes (counties) were more likely than urban parishes to have higher pesticide hospitalization rates (OR=4.72, 95% CI 2.34, 9.54; p<0.0001). Intentional poisonings accounted for 27% of cases. Only eight cases were coded as work-related. Analyzing pesticide-related hospitalization data provides important information about some of the most severe pesticide poisoning cases. Significant findings include the elevated rate of hospitalizations among young children and men, and the large proportion of self-inflicted poisonings. Health departments and health-care providers may use these findings to target outreach and prevention activities.

Suspected adverse drug reaction reports with oral anticoagulants in Portugal: a pharmacovigilance study.

PubMed

Caldeira, Daniel; Rodrigues, Raquel; Abreu, Daisy; Anes, Ana Marta; Rosa, Mário M; Ferreira, Joaquim J

2018-04-01

In this pharmacovigilance study, we aimed to determine the incidence of spontaneously reported suspected adverse drug reactions (ADRs) related to oral anticoagulants: non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban, rivaroxaban) and vitamin K antagonists (VKA) Research design and methods: In this retrospective observational study, we extracted all the individual case safety reports related to oral anticoagulants recorded in the Portuguese Pharmacovigilance Database (January 2010 to April 2015). The annual incidence of suspected ADRs was estimated using drug exposure data. Disproportionality of reporting ADR was addressed through reporting odds ratio (ROR) and 99% confidence intervals. We appraised 794 suspected ADR (78% related to NOACs). The annual number of ADRs increased overtime with 9 ADRs/million Defined Daily Dose (DDD) at the end of 2014. The incidence of NOACs ADRs decreased from 2012 onwards. VKA showed a disproportion in 'Investigation' (ROR 0.10, 99%CI 0.05-0.22) and 'Injury, poisoning and procedural complications' (ROR 0.36, 99%CI 0.19-0.69) ADRs compared with NOACs. NOACs had a higher significant disproportion of 'Nervous system disorders' related ADRs (ROR 3.98, 99%CI 1.50-10.53). Reporting of ADRs associated with oral anticoagulants (mainly NOACs), is increasing. Exploratory disproportion analyses showed an increase of reports of nervous system ADRs with NOACs, and INR-related ADRs with VKA.

78 FR 22876 - Rodenticides; Notice of Intent To Cancel Registrations of, and Notice of Denial of Applications...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-17

... ENVIRONMENTAL PROTECTION AGENCY [FIFRA Docket No. 661; FRL-9804-2] Rodenticides; Notice of Intent To Cancel Registrations of, and Notice of Denial of Applications for, Certain Rodenticide Bait... to the Notice of Intent to Cancel Registration of, and Notice of Denial of Application for, Certain...

Avian toxicologic diagnosis

USGS Publications Warehouse

Sigurdson, C.J.; Franson, J.C.; Fudge, A.M.

2000-01-01

This chapter describes the sources and pathophysiology of some potential poisons that affect birds and summarizes useful laboratory tests. The diagnosis of poisoning in birds, as in mammals, requires a complete and accurate history, careful observation of clinical signs, and a thorough necropsy evaluation. Appropriate sample handling and analysis, based on consultation with the diagnostic toxicologist, are critical (Table 19--1). Veterinary toxicology laboratories are becoming increasingly specialized, with only certain laboratories capable of analyzing for drug residues or anticoagulants, for example. Although a local laboratory may not be able to fulfill a specific test request, they may recommend an alternative laboratory or may be willing to forward the sample. As a general rule in suspect poisoning cases, large tissue samples of liver, kidney, brain, and subcutaneous fat and of crop, proventriculus, and ventriculus contents should be collected at necropsy and frozen. Appropriate samples should be submitted frozen, with the remainder held in the freezer for possible later testing. A second set of tissues should be placed in 10% formalin for histopathologic examination.

A Tier-I leaching risk assessment of three anticoagulant compounds in the forested areas of Hawai'i.

PubMed

D'Alessio, Matteo; Wang, Tiejun; Swift, Catherine E; Shanmungam, Mohana Sundaram; Ray, Chittaranjan

2018-07-15

The anticoagulant rodenticides brodifacoum, chlorophacinone, and diphacinone have been proposed for broadcast application in some forested areas in Hawai'i to protect rare and endangered native bird species from introduced mice and rats. Groundwater resources in Hawai'i are prone to contamination due to the intrinsic aquifer vulnerability to leaching from the land surface. Because of the hydrogeologic complexity, Hawai'i uses a Tier-I leaching assessment tool, CLERS, to make registration decisions for new or existing chemicals. The CLERS tool uses soil and pesticide properties as well as water recharge through the soil profile in a GIS framework to estimate mass attenuation of the chemicals at a given depth and compares against this attenuation factor against those of a known leacher and a non-leacher. Disturbed soil samples were collected across the state of Hawai'i, including the islands of Hawai'i, Kaho'olawe, Kaua'i, Lana'i, Maui, Moloka'i, and O'ahu, with two sampling locations per island, except for Kaua'i which had three. As only limited information on chemical properties of these anticoagulants in soils is available, laboratory experiments were performed to determine the sorption capacity (K d ) and the degradation rate (T 1/2 ) of brodifacoum, chlorophacinone, and diphacinone to construct a proper chemical database. Depending on the soil type, T 1/2 values ranged between 37 and 248days for diphacinone, between 39 and 1000days for chlorophacinone, and between 72 and 462days for brodifacoum. These data were used in the CLERS tool to estimate leaching risks for these chemicals primarily in forested areas of the state where the chemicals are likely to be applied. The results from the CLERS tool indicate low risks of leaching of these three compounds into aquifers in five out of six major Hawaiian Islands. Diphacinone showed medium risk of leaching in a few remote areas in Maui. Copyright © 2018 Elsevier B.V. All rights reserved.

Autologous blood transfusion in dogs with thoracic or abdominal hemorrhage: 25 cases (2007-2012).

PubMed

Higgs, Veronica A; Rudloff, Elke; Kirby, Rebecca; Linklater, Andrew K J

2015-01-01

To describe the use and outcome following autologous blood transfusion (ABT) in dogs. Retrospective study (January 2007-July 2012). Private veterinary referral center. Twenty-five dogs that underwent ABT secondary to thoracic or abdominal hemorrhage. None. The hospital transaction database was searched using the keyword "autotransfusion" from January 2007 to July 2012. Data collected included signalment, body weight, etiology of hemorrhage, source and method of collection, volumes and method of ABT administration, use of anticoagulant, reported complications, and outcome. Twenty-five dogs were included for a total of 27 ABTs. Causes of hemorrhage included vascular trauma (14/25 dogs, 56%), ruptured tumor (8/25, 32%), and coagulopathy attributed to brodifacoum toxicosis (3/25, 12%). Autologous blood was collected from the abdominal (19/25, 76%), thoracic (5/25, 20%), or abdominal and thoracic cavities (1/25, 4%). Anticoagulant was added to the ABT blood in 13 of 25 (52%) cases. A median ABT volume of 29.3 mL/kg (range 2.9-406.9 mL/kg) was infused through either a 210 μm blood administration filter (21/27, 78%) or an 18 μm hemonate filter (6/27, 22%). Reported complications that may have been associated with ABT included hypocalcemia (4/17, 24%), hemolyzed serum (5/19, 26%), and prolonged coagulation times (4/5, 80%). These complications were considered of minimal clinical significance. Additional blood products were administered in 17 of 25 (68%) dogs. Seventeen (68%) dogs survived to discharge. Cause of death in the remaining cases was euthanasia or cardiac arrest secondary to uncontrollable hemorrhage. ABT is an adjunct to volume replacement in dogs with thoracic or abdominal hemorrhage secondary to vascular trauma, ruptured tumor, or anticoagulant rodenticide toxicosis. ABT may be used as bridge to definitive hemorrhage control, particularly when other blood products are not available or affordable. Complications may include hypocalcemia, prolonged coagulation times, and hemolysis. © Veterinary Emergency and Critical Care Society 2015.

TOXIC EXPOSURES IN CHILDREN INVOLVING LEGALLY AND ILLEGALLY COMMERCIALIZED HOUSEHOLD SANITIZERS

PubMed Central

Campos, Alessandra Marcuz de Souza; Bucaretchi, Fábio; Fernandes, Luciane Cristina Rodrigues; Fernandes, Carla Borrasca; de Capitani, Eduardo Mello; Beck, Ana Raquel Medeiros

2017-01-01

ABSTRACT Objectives: To analyze and to compare clinical repercussions of accidents involving legally and illegally commercialized household sanitizers in children under 7 years of age. Methods: A descriptive cross-sectional design was used to collect data from electronic database of a regional Poison Control Center during one year. Data were analyzed by means of descriptive non-parametric statistics and association tests. Results: The sample had 737 reported cases. Most of the accidents occurred with children under 3 years of age (median: 1 year of age; interquartile interval: 1-3 years of age), at home (92.9%), by ingestion (97.2%). Products involved were cleaning products with low toxicity and no caustic effects (38.9%); caustics (24.1%); hydrocarbons (19.3%); pesticides/rodenticides (16.6%), and other products (1.1%). Seventy accidents were due to exposures to illegal products, mainly caustics (n=47) and rodenticides (n=15). Among the 337 children presenting post-exposure clinical manifestations, the most frequent were vomiting (n=125), oral burns (n=74), cough (n=35), drooling (n=26), and abdominal pain (n=25). Clinical manifestations were significantly more frequent after illegal products exposure (55/70 versus 282/667, p<0.01). Nineteen children had to be hospitalized (caustics, n=17; illegal products, n=12; median time of hospitalization: 2 days), 22 were submitted to esophagogastroduodenoscopy (sodium hydroxide, n=14; illegal products, n=14); and 12 cases had endoscopic alterations (severe in 2). No deaths occurred. Conclusion: Toxic exposures owing to illegal household sanitizer products are associated with greater morbidity when compared with legal ones. PMID:28977311

Causes of mortality and pathological lesions observed post-mortem in red squirrels (Sciurus vulgaris) in Great Britain

PubMed Central

2013-01-01

Background The red squirrel population in Great Britain has declined dramatically in recent decades, principally due to squirrelpox. Concern exists that red squirrels may become extinct nationally and, as there has been limited research in to diseases other than squirrelpox, this study aimed to identify additional causes of mortality. Results Post-mortem examinations on 163 red squirrels found dead on Isle of Wight (IoW) England, in Scotland and at other locations in Great Britain showed that 41.7% (n = 68) were killed by road traffic and 9.2% (n = 15) by predators, principally domestic cats and dogs. The overall male/female ratio was 1.08/1. Fleas were recorded on 34.9% of IoW squirrels and on 43.8% of Scottish squirrels but sucking lice and ixodid ticks were only seen on Scottish squirrels. Bacterial infections were significant, particularly in association with respiratory disease (n = 16); two squirrels died of Bordetella bronchiseptica bronchopneumonia. Cases of fatal exudative dermatitis (n = 5) associated with a lukM-positive clone of Staphylococcus aureus occurred only on the IoW. Toxoplasmosis (n = 12) was also confined to IoW where it was responsible for almost one tenth (9.5%) of all deaths. Hepatozoonosis was common, especially in IoW squirrels, but was not considered a primary cause of mortality. Hepatic capillariasis affected four IoW squirrels and one from Scotland. Fungal infections included oral candidiasis, adiaspiromycosis and pulmonary phaeohyphomycosis. Neoplastic conditions diagnosed were: pulmonary carcinoma, gastric spindle cell tumour, renal papillary adenoma and trichoepithelioma. Epidermal hyperplasia of unknown aetiology was seen in squirrels showing crusty lesions of the ear pinnae on IoW (n = 3) and Brownsea Island (n = 1), associated in two cases with cutaneous wart-like growths. Miscellaneous diagnoses included chylothorax, electrocution, intussusception, suspected cholecalciferol rodenticide poisoning and foetal death and mummification. No cases of squirrelpox were diagnosed. Conclusions Red squirrels in Britain suffer premature or unnatural mortality due to a number of conditions in addition to squirrelpox, many of which result, directly or indirectly, from human activities: road traffic trauma, pet predation, toxoplasmosis, trap injuries, rodenticide poisoning and electrocution accounted for 61% of all recorded mortality in this study. Red squirrels are also affected by several diseases of unknown aetiology which merit further research. PMID:24238087

Pesticide Exposure in Children

PubMed Central

Roberts, James R.; Karr, Catherine J.

2018-01-01

Pesticides are a collective term for a wide array of chemicals intended to kill unwanted insects, plants, molds, and rodents. Food, water, and treatment in the home, yard, and school are all potential sources of children’s exposure. Exposures to pesticides may be overt or subacute, and effects range from acute to chronic toxicity. In 2008, pesticides were the ninth most common substance reported to poison control centers, and approximately 45% of all reports of pesticide poisoning were for children. Organophosphate and carbamate poisoning are perhaps the most widely known acute poisoning syndromes, can be diagnosed by depressed red blood cell cholinesterase levels, and have available antidotal therapy. However, numerous other pesticides that may cause acute toxicity, such as pyrethroid and neonicotinoid insecticides, herbicides, fungicides, and rodenticides, also have specific toxic effects; recognition of these effects may help identify acute exposures. Evidence is increasingly emerging about chronic health implications from both acute and chronic exposure. A growing body of epidemiological evidence demonstrates associations between parental use of pesticides, particularly insecticides, with acute lymphocytic leukemia and brain tumors. Prenatal, household, and occupational exposures (maternal and paternal) appear to be the largest risks. Prospective cohort studies link early-life exposure to organophosphates and organochlorine pesticides (primarily DDT) with adverse effects on neurodevelopment and behavior. Among the findings associated with increased pesticide levels are poorer mental development by using the Bayley index and increased scores on measures assessing pervasive developmental disorder, inattention, and attention-deficit/hyperactivity disorder. Related animal toxicology studies provide supportive biological plausibility for these findings. Additional data suggest that there may also be an association between parental pesticide use and adverse birth outcomes including physical birth defects, low birth weight, and fetal death, although the data are less robust than for cancer and neurodevelopmental effects. Children’s exposures to pesticides should be limited as much as possible. PMID:23184105

78 FR 8123 - Rodenticides; Notice of Intent To Cancel Registrations of, and Notice of Denial of Applications...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-05

... To Cancel Registrations of, and Notice of Denial of Applications for, Certain Rodenticide Bait...) of FIFRA, EPA hereby announces the denial of applications for registration of 2 products identified... 8124

Retention time of chlorophacinone in black-tailed prairie dogs informs secondary hazards from a prairie dog rodenticide bait.

PubMed

Witmer, Gary W; Snow, Nathan P; Moulton, Rachael S

2016-04-01

Secondary toxicity in mammals and birds that consume animals containing residues of anticoagulant rodenticides represents a persistent conflict between conservation, agriculture and environmental contamination. Chlorophacinone residues in black-tailed prairie dogs (Cynomys ludovicianus) represent a secondary exposure hazard to predatory and scavenging avian and mammalian species in the Central Plains of the United States, especially considering efforts to re-establish black-footed ferrets (Mustela nigripes). Rozol(®) Prairie Dog Bait (chlorophacinone 0.005%) is registered to control black-tailed prairie dogs in ten states throughout the midwestern and western United States. We fed Rozol Prairie Dog Bait to captive black-tailed prairie dogs for 2 days and analyzed their livers and whole bodies (without livers) for chlorophacinone residue on days 3, 5, 7, 9, 11, 14, 18 and 27 post-exposure. We found the greatest levels of residues in livers (x‾ = 5.499 mg kg(-1) ) and whole bodies (x‾ = 1.281 mg kg(-1) ) on day 3. Residues in both tissues declined rapidly over time, with estimated half-lives of approximately 6 days post-exposure. However, a risk assessment of secondary toxicity to non-target mammals indicated acute risks for mammalian species up to 27 days post-exposure and negligible risks for birds. The results suggest that the greatest risk of secondary toxicity occurs ≤14 days post-application of Rozol Prairie Dog Bait and declines thereafter. This corresponds to the time when chlorophacinone residues are high, and prairie dogs exhibit signs of intoxication and are perhaps most susceptible to predation and scavenging. These results confirm that Rozol Prairie Dog Bait should not be used in areas where black-footed ferrets or other sensitive species occur. Published 2015. This article is a U.S. Government work and is in the public domain in the USA. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Studies on the fate of flocoumafen in the Japanese quail (Coturnix coturnix japonica).

PubMed

Huckle, K R; Warburton, P A; Forbes, S; Logan, C J

1989-01-01

1. 14C-Flocoumafen, administered to Japanese quail as a single oral or i.p. dose, was rapidly and extensively eliminated in excreta; most was eliminated within 24 h. Extensive metabolism of the rodenticide was seen, with at least 8 metabolites detected; unchanged flocoumafen comprised 9% dose. The elimination kinetics and metabolic profiles were qualitatively similar after oral and i.p. dosing. 2. The major metabolites (60% dose) were labile to beta-glucuronidase, liberating aglycones with identical chromatographic mobilities to those of the unchanged flocoumafen isomers. 3. Radioactivity was retained mostly in the liver; largely as unchanged flocoumafen associated with the mitochondrial and microsomal fractions. Elimination of radioactivity from most tissues was biphasic with an initially rapid depletion (5 days) followed by a slow terminal elimination phase. The elimination half life from liver was greater than 100 days. 4. Livers of quail receiving extended dietary exposure to flocoumafen at 5, 15 and 50 ppm had concentrations of flocoumafen (1.0 nmol/g) that were independent of dose, indicating a capacity-limited binding site. These hepatic concentrations were similar to those after a single oral dose and were also similar to those in rats. The data indicate the presence in quail liver of a saturable high affinity flocoumafin binding site with similar characteristics and capacity to that in the rat. 5. The selective toxicity of flocoumafen to rats (highly toxic) and quail (moderately toxic) appears to arise from differences in metabolism rather than from anticoagulant binding in the liver. When hepatic binding sites of rats are saturated anticoagulant action becomes lethal, whereas quail are able to survive and extensively metabolize the compound.

Black-tailed prairie dog populations one year after treatment with rodenticides

Treesearch

Anthony D. Apa; Daniel W. Uresk; Raymond L. Linder

1990-01-01

Three rodenticide treatments, zinc phosphide with prebait, strychnine with prebait, and strychnine without prebait, were applied to black-tailed prairie dog (Cynomys ludovicianus) colonies in west central South Dakota. Results were compared immediately posttreatment and for one year after application. Zinc phosphide was the most effective for...

Effects of prairie dog rodenticides on deer mice in western South Dakota

Treesearch

Michele S. Deisch; Daniel W. Uresk; Raymond L. Linder

1990-01-01

Mortality of nontarget small mammals was determined after application of three black-tailed prairie dog (Cynomys Zudovicianus) rodenticide treatments (prebaited zinc phosphide, prebaited strychnine, and strychnine alone) in western South Dakota. Immediate (September 1983) and long-term (September 1983 through August 1984) impacts on deer mouse (...

Impacts of black-tailed prairie dog rodenticides on nontarget passerines

Treesearch

Anthony D. Apa; Daniel W. Uresk; Raymond L. Linder

1991-01-01

In 1983 zinc phosphide, strychnine with prebait, and strychnine without prebait were applied to black-tailed prairie dog (Cynomys Zudovicianus) colonies in west central South Dakota. Short-term (four days later) and long-term (one year later) impacts of the rodenticides on Horned Larks (Eremophila alpestris) and other...

PRN 94-7: Label Improvement Program for the Revision of Use Directions for Commensal Rodenticides and Statement of the Agency's Policies on the Use of Rodenticide Bait Stations

EPA Pesticide Factsheets

This Notice requires registrants of certain pesticide products claimed to control commensal rodents and registered under FIFRA to revise the labeling of such products to bear certain statements concerning tamper-resistant bait stations.

76 FR 4653 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

... Activities; Submission to OMB for Review and Approval; Comment Request; Recordkeeping Requirements for... Insecticide, Fungicide, and Rodenticide Act (FIFRA); EPA ICR No. 0143.11, OMB Control No. 2070-0028 AGENCY... Devices Under Section 8 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). ICR numbers...

Demography of black-tailed prairie dog populations reoccupying sites treated with rodenticide

Treesearch

R. P. Cincotta; Daniel W. Uresk; R. M. Hansen

1987-01-01

A rodenticide, zinc phosphide, was applied to remove black-tailed prairie dogs (Cynomys ludovicianus) from 6 haofa prairie dog colony in southwestern South Dakota. Another adjacent 6 ha was left untreated. The removal experiment was repeated two consecutive years. Contingency table analysis showed that the resultant population was not homogeneous;...

A synthetic review of notoedres species mites and mange

USGS Publications Warehouse

Foley, Janet E.; Serieys, L.E.; Stephenson, N.; Riley, S.; Foley, C.; Jennings, M.; Wengert, G.; Vickers, W.; Boydston, Erin E.; Lyren, Lisa L.; Moriarty, J.; Clifford, D.L.

2016-01-01

Notoedric mange, caused by obligately parasitic sarcoptiform Notoedres mites, is associated with potentially fatal dermatitis with secondary systemic disease in small mammals, felids and procyonids among others, as well as an occasional zoonosis. We describe clinical spectra in non-chiropteran hosts, review risk factors and summarize ecological and epidemiological studies. The genus is disproportionately represented on rodents. Disease in felids and procyonids ranges from very mild to death. Knowledge of the geographical distribution of the mites is highly inadequate, with focal hot spots known for Notoedres cati in domestic cats and bobcats. Predisposing genetic and immunological factors are not known, except that co-infection with other parasites and anticoagulant rodenticide toxicoses may contribute to severe disease. Treatment of individual animals is typically successful with macrocytic lactones such as selamectin, but herd or wildlife population treatment has not been undertaken. Transmission requires close contact and typically is within a host species. Notoedric mange can kill half all individuals in a population and regulate host population below non-diseased density for decades, consistent with frequency-dependent transmission or spillover from other hosts. Epidemics are increasingly identified in various hosts, suggesting global change in suitable environmental conditions or increased reporting bias.

Effects of two prairie dog rodenticides on ground-dwelling invertebrates in western South Dakota

Treesearch

Michele S. Deisch; Daniel W. Uresk; Raymond L. Linder

1989-01-01

Immediate and long-term effects of 3 rodenticide treatments on nontarget invertebrates were evaluated on prairie dog colonies. Immediate impacts indicated zinc phosphide reduced ants, strychnine alone reduced wolf spiders, and prebaited strychnine had no impacts. Long-term changes showed increases in wolf spiders and ground beetles and densities were contributed to...

Pesticide poisoning.

PubMed

Goel, Ashish; Aggarwal, Praveen

2007-01-01

Acute poisoning with pesticides is a global public health problem and accounts for as many as 300,000 deaths worldwide every year. The majority of deaths occur due to exposure to organophosphates, organochlorines and aluminium phosphide. Organophosphate compounds inhibit acetylcholinesterase resulting in acute toxicity. Intermediate syndrome can develop in a number of patients and may lead to respiratory paralysis and death. Management consists of proper oxygenation, atropine in escalating doses and pralidoxime in high doses. It is Important to decontaminate the skin while taking precautions to avoid secondary contamination of health personnel. Organochlorine pesticides are toxic to the central nervous system and sensitize the myocardium to catecholamines. Treatment involves supportive care and avoiding exogenous sympathomimetic agents. Ingestion of paraquat causes severe inflammation of the throat, corrosive injury to the gastrointestinal tract, renal tubular necrosis, hepatic necrosis and pulmonary fibrosis. Administration of oxygen should be avoided as it produces more fibrosis. Use of immunosuppressive agents have improved outcome in patients with paraquat poisoning. Rodenticides include thallium, superwarfarins, barium carbonate and phosphides (aluminium and zinc phosphide). Alopecia is an atypical feature of thallium toxicity. Most exposures to superwarfarins are harmless but prolonged bleeding may occur. Barium carbonate Ingestion can cause severe hypokalaemia and respiratory muscle paralysis. Aluminium phosphide is a highly toxic agent with mortality ranging from 37% to 100%. It inhibits mitochondrial cytochrome c oxidase and leads to pulmonary and cardiac toxicity. Treatment is supportive with some studies suggesting a beneficial effect of magnesium sulphate. Pyrethroids and insect repellants (e.g. diethyltoluamide) are relatively harmless but can cause toxic effects to pulmonary and central nervous systems. Ethylene dibromide-a highly toxic, fumigant pesticide-produces oral ulcerations, followed by liver and renal toxicity, and is almost uniformly fatal. Physicians working in remote and rural areas need to be educated about early diagnosis and proper management using supportive care and antidotes, wherever available.

Stability of carboxyhemoglobin in stored and mailed blood samples.

PubMed

Hampson, Neil B

2008-02-01

Elevated blood carboxyhemoglobin (COHb) levels are used to confirm a clinical diagnosis of exposure to carbon monoxide (CO) and, in some instances, assess severity of poisoning. However, many hospital laboratories cannot measure COHb because they do not have CO-oximeters. In such instances, blood samples are often sent to outside laboratories or with a transported patient for measurement at the receiving hospital. This study was conducted to assess the stability of COHb in stored and mailed blood samples anticoagulated with heparin. Adult human blood was drawn into standard sample tubes anticoagulated with sodium heparin. Carbon monoxide gas was infused to raise the COHb level to 25% to 35%. Samples were then refrigerated or stored at room temperature, and serial COHb determinations were performed for 28 days. Additional samples were measured after being mailed locally or across the United States and back. No significant changes in COHb levels were seen in samples stored either in refrigeration or at room temperature over a period of 28 days or in samples shipped without refrigeration locally or across the United States. Carboxyhemoglobin levels in whole blood samples anticoagulated with heparin are stable with or without refrigeration for up to 4 weeks. If COHb measurement capability is not available, such samples may be shipped or transported with patients with confidence that the COHb level will be stable when measured at a later time.

A review of episodes of zinc phosphide toxicosis in wild geese (Branta spp.) in Oregon (2004−2011)

USGS Publications Warehouse

Bildfell, Rob J.; Rumbeiha, Wilson K.; Schuler, Krysten L.; Meteyer, Carol U.; Wolff, Peregrine L.; Gillin, Colin M.

2013-01-01

Epizootic mortality in several geese species, including cackling geese (Branta hutchinsii) and Canada geese (Branta canadensis), has been recognized in the Willamette Valley of Oregon for over a decade. Birds are generally found dead on a body of water or are occasionally observed displaying neurologic clinical signs such as an inability to raise or control the head prior to death. Investigation of these epizootic mortality events has revealed the etiology to be accidental poisoning with the rodenticide zinc phosphide (Zn3P2). Gross and histologic changes are restricted to acute pulmonary congestion and edema, sometimes accompanied by distension of the upper alimentary tract by fresh grass. Geese are unusually susceptible to this pesticide; when combined with an epidemiologic confluence of depredation of specific agricultural crops by rodents and seasonal avian migration pathways, epizootic toxicosis may occur. Diagnosis requires a high index of suspicion, appropriate sample collection and handling, plus specific test calibration for this toxicant. Interagency cooperation, education of farmers regarding pesticide use, and enforcement of regulations has been successful in greatly decreasing these mortality events since 2009.

Warfarin Poisoning with Delayed Rebound Toxicity.

PubMed

Berling, Ingrid; Mostafa, Ahmed; Grice, Jeffrey E; Roberts, Michael S; Isbister, Geoffrey K

2017-02-01

Intentional poisoning with warfarin is not the same as over-anticoagulation, for which guidelines exist. The coagulopathy resulting from a warfarin overdose is reversed with vitamin K 1 , the dose and timing of which is often guided by experience with the management of over-anticoagulation with warfarin therapy, rather than acute overdose. We report a case of a 50-year-old man who ingested an unknown amount of his warfarin, venlafaxine, and paracetamol. He presented with an international normalized ratio (INR) of 2.5, which steadily increased over 24 h to 7, despite receiving an initial 1 mg of vitamin K 1 . He was then treated with 5 mg vitamin K 1 , and once the INR returned to 4.5, 40 h post ingestion, he was discharged home. He was also treated with a full course of acetylcysteine for the paracetamol overdose. The following day his INR rebounded to 8.5 and he suffered a spontaneous epistaxis requiring readmission; he was treated with low titrated doses of vitamin K 1 . The warfarin concentration was 74.6 μg/mL 26 h post ingestion and decreased to 3.7 μg/mL over 72 h. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case highlights the risk of a rebound elevated INR even 3 days after acute warfarin overdose despite treatment with vitamin K 1 . Understanding the pharmacokinetics of vitamin K 1 in comparison with warfarin, repeat INR testing, and continued treatment with oral vitamin K 1 may help avoid complications of rebound coagulopathy in warfarin overdose. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Impacts of rodenticide and insecticide toxicants from marijuana cultivation on fisher survival rates in the Sierra National Forest, California.

Treesearch

Craig Thompson; Kathryn Purcell

2013-01-01

Secondary exposure of wildlife to pesticides has been well documented, yet exposure is typically associated with agricultural or wildland-urban interface areas. Wildlife in undeveloped areas is generally presumed free from risk. In 2009, a male fisher was found dead in the Sierra National Forest and subsequent necropsy revealed that the animal died of acute rodenticide...

Final Natural Resource Actions Environmental Assessment

DTIC Science & Technology

2005-06-22

populations through use of insecticides and rodenticides would be accomplished under the supervision of the Base Pest Management Office and coordinated... Insecticide , Fungicide, and Rodenticide Act; DoD Directive 4150.7, DoD Pest Management Program; AFI 32-1053, Pest Management Program; and the North... insecticide and herbicide. Grand Forks AFB constructed a 2,400-square-foot pest management facility in 1996 in accor- dance with the guidelines

Warfarin Toxicity and Individual Variability—Clinical Case

PubMed Central

Piatkov, Irina; Rochester, Colin; Jones, Trudi; Boyages, Steven

2010-01-01

Warfarin is a widely used anticoagulant in the treatment and prevention of thrombosis, in the treatment for chronic atrial fibrillation, mechanical valves, pulmonary embolism, and dilated cardiomyopathy. It is tasteless and colorless, was used as a poison, and is still marketed as a pesticide against rats and mice. Several long-acting warfarin derivatives—superwarfarin anticoagulants—such as brodifacoum, diphenadione, chlorophacinone, bromadiolone, are used as pesticides and can produce profound and prolonged anticoagulation. Several factors increase the risk of warfarin toxicity. However, polymorphisms in cytochrome P450 genes and drug interactions account for most of the risk for toxicity complications. Each person is unique in their degree of susceptibility to toxic agents. The toxicity interpretation and the health risk of most toxic substances are a subject of uncertainty. Genetically determined low metabolic capacity in an individual can dramatically alter the toxin and metabolite levels from those normally expected, which is crucial for drugs with a narrow therapeutic index, like warfarin. Personalized approaches in interpretation have the potential to remove some of the scientific uncertainties in toxicity cases. PMID:22069565

Palatability and efficacy of bromadiolone rodenticide block bait previously exposed to environmental conditions.

PubMed

Nakagawa, Lia; de Masi, Eduardo; Narciso, Emerson; Neto, Hildebrando Montenegro; Papini, Solange

2015-10-01

In São Paulo city, rodent infestation is considered to be a serious public health problem and is the object of a municipal rodent control programme. One of the most important routine methods involves baiting in sewers, using bromadiolone block bait in a pulsed baiting strategy. It has been observed that, after each pulse, bait is not always consumed, and its appearance is altered, which has led to concerns about efficacy. We assessed whether exposure to sewer conditions influences the palatability and efficacy of rodenticide baits to Norway rats (Rattus norvegicus). Baits containing bromadiolone as active ingredient were placed in sewers, removed after 30 days and offered to rats in a two-choice food trial and a no-choice food trial. The appearance of the rodenticide baits changed after 30 days exposure to sewer conditions, but they continued to be palatable and effective against rats. The level of mortality was considered to be satisfactory, 75% in the two-choice food trial and 100% in the no-choice food trial. Results support the reuse of rodenticide block bait in rodent control. It seems to be justified to continue using/reuse baits even when their appearance has changed after 30 days exposure in sewer systems. © 2014 Society of Chemical Industry.

Dietary supplement adverse events: report of a one-year poison center surveillance project.

PubMed

Haller, Christine; Kearney, Tom; Bent, Stephen; Ko, Richard; Benowitz, Neal; Olson, Kent

2008-06-01

The safety and efficacy of dietary supplements is of growing concern to regulators, health-care providers and consumers. Few scientific data exist on clinical effects and potential toxicities of marketed products. Harmful supplements may not be identified for months or years with existing adverse event monitoring mechanisms. Retrospective review of poison center statistics to capture supplement-associated toxicity also has limitations. We collaborated with the FDA Center for Food Safety and Nutrition (CFSAN) to conduct a 1-year prospective surveillance study of dietary supplement-related poison control center calls in 2006. Prompt follow-up of symptomatic cases, laboratory analysis of implicated dietary supplements, and causality assessment by a case review expert panel were performed. Of 275 dietary supplements calls, 41% involved symptomatic exposures; and two-thirds were rated as probably or possibly related to supplement use. Eight adverse events required hospital admission. Sympathomimetic toxicity was most common, with caffeine products accounting for 47%, and yohimbe products accounting for 18% of supplement-related symptomatic cases. Suspected drug-herb interactions occurred in 6 cases, including yohimbe co-ingested with buproprion (1) and methamphetamine (3), and additive anticoagulant/antiplatelet effects of NSAIDs taken with fish oils (1) and ginkgo (1). Laboratory analysis identified a pharmacologically active substance in 4 cases; supplement toxicity was ruled unlikely when analytical testing was negative in 5 cases. Most supplement-related adverse events were minor. Clinically significant toxic effects were most frequently reported with caffeine and yohimbe-containing products. Active surveillance of poison control center reports of dietary supplement adverse events enables rapid detection of potentially harmful products, which may facilitate regulatory oversight.

Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABAA receptors

PubMed Central

Shakarjian, Michael P.; Velíšková, Jana; Stanton, Patric K.; Velíšek, Libor

2012-01-01

Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic-clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic-clonic seizures or lethality, but increased the number of clonic seizures. Doubling the ketamine dose decreased tonic-clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABAA receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists are more likely to be effective in treating TMDT poisoning. PMID:23022509

Control of invasive rats on islands and priorities for future action.

PubMed

Duron, Quiterie; Shiels, Aaron B; Vidal, Eric

2017-08-01

Invasive rats are one of the world's most successful animal groups that cause native species extinctions and ecosystem change, particularly on islands. On large islands, rat eradication is often impossible and population control, defined as the local limitation of rat abundance, is now routinely performed on many of the world's islands as an alternative management tool. However, a synthesis of the motivations, techniques, costs, and outcomes of such rat-control projects is lacking. We reviewed the literature, searched relevant websites, and conducted a survey via a questionnaire to synthesize the available information on rat-control projects in island natural areas worldwide to improve rat management and native species conservation. Data were collected from 136 projects conducted over the last 40 years; most were located in Australasia (46%) and the tropical Pacific (25%) in forest ecosystems (65%) and coastal strands (22%). Most of the projects targeted Rattus rattus and most (82%) were aimed at protecting birds and endangered ecosystems. Poisoning (35%) and a combination of trapping and poisoning (42%) were the most common methods. Poisoning allows for treatment of larger areas, and poison projects generally last longer than trapping projects. Second-generation anticoagulants (mainly brodifacoum and bromadiolone) were used most often. The median annual cost for rat-control projects was US$17,262 or US$227/ha. Median project duration was 4 years. For 58% of the projects, rat population reduction was reported, and 51% of projects showed evidence of positive effects on biodiversity. Our data were from few countries, revealing the need to expand rat-control distribution especially in some biodiversity hotspots. Improvement in control methods is needed as is regular monitoring to assess short- and long-term effectiveness of rat-control. © 2016 Society for Conservation Biology.

Quantitative Analysis of Tetramethylenedisulfotetramine ("Tetramine") Spiked into Beverages by Liquid Chromatography Tandem Mass Spectrometry with Validation by Gas Chromatography Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Owens, J; Hok, S; Alcaraz, A

Tetramethylenedisulfotetramine, commonly known as tetramine, is a highly neurotoxic rodenticide (human oral LD{sub 50} = 0.1 mg/kg) used in hundreds of deliberate food poisoning events in China. Here we describe a method for quantitation of tetramine spiked into beverages, including milk, juice, tea, cola, and water and cleaned up by C8 solid phase extraction and liquid-liquid extraction. Quantitation by high performance liquid chromatography tandem mass spectrometry (LC/MS/MS) was based upon fragmentation of m/z 347 to m/z 268. The method was validated by gas chromatography mass spectrometry (GC/MS) operated in SIM mode for ions m/z 212, 240, and 360. The limitmore » of quantitation was 0.10 {micro}g/mL by LC/MS/MS versus 0.15 {micro}g/mL for GC/MS. Fortifications of the beverages at 2.5 {micro}g/mL and 0.25 {micro}g/mL were recovered ranging from 73-128% by liquid-liquid extraction for GC/MS analysis, 13-96% by SPE and 10-101% by liquid-liquid extraction for LC/MS/MS analysis.« less

[Study of the interaction mechanism between brodifacoum and DNA by spectroscopy].

PubMed

Duan, Yun-qing; Min, Shun-geng

2009-04-01

The interaction between brodifacoum (3-[3-(4'-bromophenyl-4) 1,2,3,4-tetralin-10]-4-hydroxyl-coumarin) (BDF), an anticoagulant rodenticide, and calf thymus DNA (ct-DNA) was studied by UV spectrum and fluorescence spectrum. The results were summarized as follows: There was a hypochromic effect of low concentration ct-DNA on the UV spectra. The fluorescence quenching studies showed a regular decrease in the fluorescence intensity after addition of ct-DNA by the static quenching mode with a quenching constant (Ksv) of 1.21 x 10(4) L x mol(-1) at 27 degrees C. The BDF possibly bonded to ct-DNA mainly via Van der Waals forces by the corresponding thermodynamics parameter. KI quenching experiment found that there was not obvious protection of ct-DNA to BDF. The fluorescence intensity of BDF/ct-DNA system changed with the variation in ionic strength Quenching of ct-DNA on the fluorescence of BDF/beta-CD inclusion complex was reduced in contrast with the free BDF, which showed that beta-CD could provide BDF with protection. So the comprehensive interaction mode of BDF with ct-DNA may be the groove binding by the above results. It was indicated that there had been static-electro interaction between BDF and ct-DNA at the same time. The conjunct action of Van der Waals forces and electrostatic attraction favorably provide BDF bonding interaction in the groove of ct-DNA.

Results of laboratory testing for diphacinone in seawater, fish, invertebrates, and soil following aerial application of rodenticide on Lehua Island, Kauai County, Hawaii, January 2009

USGS Publications Warehouse

Orazio, Carl E.; Tanner, Michael J.; Swenson, Chris; Herod, Jeffrey J.; Dunlevy, Peter; Gale, Robert W.

2009-01-01

In January 2009, rodenticide bait (Ramik Green pellets) containing the active ingredient diphacinone was aerially applied to Lehua Island. Reported herein are the results of laboratory analyses to determine diphacinone concentrations in samples of seawater, fillet of fish, soft tissue of limpets (opihi), whole-body crabs, and soil collected from Lehua Island, Kauai County, Hawaii, after aerial application of the rodenticide bait. Diphacinone was specifically chosen because of its low toxicity to nontarget organisms. Its use on Lehua Island is the second time it has ever been used for an aerial application to eradicate rodents. Testing of the Lehua Island samples for diphacinone utilized high-performance liquid chromatography with photodiode array detection. No detectable concentrations of diphacinone were found in any of the samples from Lehua Island. The limits of detection for diphacinone were 0.4 nanograms per milliliter (parts per billion) seawater, 15 nanograms per gram (dry weight) soil, 20 nanograms per gram (parts per billion) fish fillet, 13 nanograms per gram whole crab, and 34 nanograms per gram soft tissue limpet.

Wartime rat control, rodent ecology, and the rise and fall of chemical rodenticides.

PubMed

Keiner, Christine

2005-09-01

The story of how World War II stimulated the development of DDT, and the ensuing postwar dependence on such chemical insecticides, is well known. However, less recognition has been given to the wartime efforts to synthesize new rodenticides to fight rat-borne epidemics. Baltimore, Maryland served as the site for field tests of the powerful new compound alpha naphthyl thiourea (ANTU) from 1942-1946. This experimental campaign sparked debates over the efficacy of controlling rats via chemical warfare instead of environmental sanitation, which led to the ironic conclusion that urban rat control demanded an ecological, rather than technological, approach.

Combined Diazepam and MK-801 Therapy Provides Synergistic Protection from Tetramethylenedisulfotetramine-induced Tonic-Clonic Seizures and Lethality in Mice

PubMed Central

Shakarjian, Michael P.; Ali, Mahil S.; Velíšková, Jana; Stanton, Patric K.; Heck, Diane E.; Velíšek, Libor

2015-01-01

The synthetic rodenticide, tetramethylenedisulfotetramine (TMDT), is a persistent and highly lethal GABA-gated Cl− channel blocker. TMDT is clandestinely produced, remains popular in mainland China, and causes numerous unintentional and deliberate poisonings worldwide. TMDT is odorless, tasteless, and easy to manufacture, features that make it a potential weapon of terrorism. There is no effective treatment. We previously characterized the effects of TMDT in C57BL/6 mice and surveyed efficacies of GABAergic and glutamatergic anticonvulsant treatments. At 0.4 mg/kg i.p., TMDT produced neurotoxic symptomatology consisting of twitches, clonic and tonic-clonic seizures, often progressing to status epilepticus and death. If administered immediately after the occurrence of the first clonic seizure, the benzodiazepine diazepam (DZP) effectively prevented all subsequent seizure symptoms, whereas the NMDA receptor antagonist dizocilpine (MK-801) primarily prevented tonic-clonic seizures. The latter agent, however, appeared to be more effective at preventing delayed death. The present study further explored these phenomena, and characterized the therapeutic actions of DZP and MK-801 as combinations. Joint treatment with both DZP and MK-801 displayed synergistic protection against tonic-clonic seizures and 24 hour lethality as determined by isobolographic analysis. Clonic seizures, however, remained poorly controlled. A modification of the treatment regimen, where DZP was followed 10 min later by MK-801, yielded a reduction in both types of seizures and improved overall outcome. Simultaneous monitoring of subjects via EEG and videography confirmed effectiveness of this sequential regimen. We conclude that TMDT blockage at GABAA receptors involves early activation of NMDA receptors, which contribute to persistent ictogenic activity. Our data predict that a sequential combination treatment with DZP followed by MK-801 will be superior to either individual therapy with, or simultaneous administration of, these two agents in treating TMDT poisoning. PMID:25783504

An Enigmatic Case of Acute Mercury Poisoning: Clinical, Immunological Findings and Platelet Function.

PubMed

Kleffner, Ilka; Eichler, Susann; Ruck, Tobias; Schüngel, Lisa; Pfeuffer, Steffen; Polzer, Philipp; Dittrich, Ralf; Dziewas, Rainer; Gross, Catharina C; Göbel, Kerstin; Wiendl, Heinz; Kehrel, Beate E; Meuth, Sven G

2017-01-01

Severe mercury intoxication is very rare in developed countries, but still occurs as the result of volatile substance abuse, suicide attempts, occupational hazards, or endemic food ingestion as reported in the cases of public health disasters in Iraq and in Minamata Bay, Japan. Here, we describe the dramatic physical and cognitive decline of a 23-year-old patient caused by a severe methyl mercury (MeHg) intoxication of unknown origin. We show serial magnetic resonance imaging (MRI) of the patient's brain, as well as ex vivo analyses of blood and cerebrospinal fluid including multicolor flow cytometric measurements, functional assays of hemostaseologic efficacy, and evaluation of regulatory effector molecules. Together with the clinical history, our findings show the progressive neuronal degeneration accompanying the deterioration of the patient. Moreover, the ex vivo analyses display alterations of thrombocyte function and coagulation, as well as an immunological milieu facilitating autoimmunity. Despite the successful reduction of the MeHg concentration in the patient's blood with erythrocyte apheresis and chelator therapy, his condition did not improve and led to a persistent vegetative state. This case illustrates the neurotoxicity of MeHg following severe intoxication for the first time by serial MRI. Data on immune-cell and thrombocyte function as well as on coagulation in mercury poisoning reveal potential implications for anticoagulation and immunomodulatory treatment.

Cytochrome P450-mediated warfarin metabolic ability is not a critical determinant of warfarin sensitivity in avian species: In vitro assays in several birds and in vivo assays in chicken.

PubMed

Watanabe, Kensuke P; Kawata, Minami; Ikenaka, Yoshinori; Nakayama, Shouta M M; Ishii, Chihiro; Darwish, Wageh Sobhi; Saengtienchai, Aksorn; Mizukawa, Hazuki; Ishizuka, Mayumi

2015-10-01

Coumarin-derivative anticoagulant rodenticides used for rodent control are posing a serious risk to wild bird populations. For warfarin, a classic coumarin derivative, chickens have a high median lethal dose (LD50), whereas mammalian species generally have much lower LD50. Large interspecies differences in sensitivity to warfarin are to be expected. The authors previously reported substantial differences in warfarin metabolism among avian species; however, the actual in vivo pharmacokinetics have yet to be elucidated, even in the chicken. In the present study, the authors sought to provide an in-depth characterization of warfarin metabolism in birds using in vivo and in vitro approaches. A kinetic analysis of warfarin metabolism was performed using liver microsomes of 4 avian species, and the metabolic abilities of the chicken and crow were much higher in comparison with those of the mallard and ostrich. Analysis of in vivo metabolites from chickens showed that excretions predominantly consisted of 4'-hydroxywarfarin, which was consistent with the in vitro results. Pharmacokinetic analysis suggested that chickens have an unexpectedly long half-life despite showing high metabolic ability in vitro. The results suggest that the half-life of warfarin in other bird species could be longer than that in the chicken and that warfarin metabolism may not be a critical determinant of species differences with respect to warfarin sensitivity. © 2015 SETAC.

Anti-Xa activity in apixaban overdose: a case report.

PubMed

Barton, James; Wong, Anselm; Graudins, Andis

2016-11-01

Apixaban is a novel oral anticoagulation agent that exerts its effect through direct factor Xa inhibition. We present a case of multi-drug overdose including apixaban with associated apixaban concentrations. A 53 year-old man presented to our metropolitan hospital following a deliberate self-poisoning with 200 mg apixaban, 35 mg ramipril, 105 mg bisoprolol, 280 mg atorvastatin, 6 mg colchicine, 37.4 mg magnesium, 4 × 500 mg paracetamol/9.5 mg codeine/5 mg phenylephrine and alcohol. He developed hypotension that was treated with noradrenaline. His initial and peak apixaban concentration was 1022.6 ng/ml and was associated with only minor bleeding from his femoral central line insertion site, which improved with local compression. Vitamin K 10 mg (at 9 h post-ingestion) and Prothrombinex-VF 2000 units (at 13 h post-ingestion) were also administered without any observed effect on coagulation studies. Apixaban elimination appeared to display first-order kinetics with an elimination half-life of 7.4 h. His plasma apixaban concentration was within the therapeutic dose range 10 h post-ingestion and he recovered uneventfully. A case of apixaban overdose with associated apixaban concentrations is presented. There was rapid resolution of anticoagulation with no demonstrable benefit of currently available clotting factor replacement.

Pesticide Reevaluation

EPA Pesticide Factsheets

Learn about the process for periodically evaluating registered pesticides to ensure they meet current science standards for risk assessment, as required by the Federal Insecticide Fungicide and Rodenticide Act.

An Enigmatic Case of Acute Mercury Poisoning: Clinical, Immunological Findings and Platelet Function

PubMed Central

Kleffner, Ilka; Eichler, Susann; Ruck, Tobias; Schüngel, Lisa; Pfeuffer, Steffen; Polzer, Philipp; Dittrich, Ralf; Dziewas, Rainer; Gross, Catharina C.; Göbel, Kerstin; Wiendl, Heinz; Kehrel, Beate E.; Meuth, Sven G.

2017-01-01

Severe mercury intoxication is very rare in developed countries, but still occurs as the result of volatile substance abuse, suicide attempts, occupational hazards, or endemic food ingestion as reported in the cases of public health disasters in Iraq and in Minamata Bay, Japan. Here, we describe the dramatic physical and cognitive decline of a 23-year-old patient caused by a severe methyl mercury (MeHg) intoxication of unknown origin. We show serial magnetic resonance imaging (MRI) of the patient’s brain, as well as ex vivo analyses of blood and cerebrospinal fluid including multicolor flow cytometric measurements, functional assays of hemostaseologic efficacy, and evaluation of regulatory effector molecules. Together with the clinical history, our findings show the progressive neuronal degeneration accompanying the deterioration of the patient. Moreover, the ex vivo analyses display alterations of thrombocyte function and coagulation, as well as an immunological milieu facilitating autoimmunity. Despite the successful reduction of the MeHg concentration in the patient’s blood with erythrocyte apheresis and chelator therapy, his condition did not improve and led to a persistent vegetative state. This case illustrates the neurotoxicity of MeHg following severe intoxication for the first time by serial MRI. Data on immune-cell and thrombocyte function as well as on coagulation in mercury poisoning reveal potential implications for anticoagulation and immunomodulatory treatment. PMID:29033890

History of drugs for thrombotic disease. Discovery, development, and directions for the future.

PubMed

Mueller, R L; Scheidt, S

1994-01-01

The history of the antithrombotic agents--aspirin, heparin, warfarin, and the thrombolytics--is a rich and lively odyssey of serendipity, perseverance, vision, and conflict involving a number of striking personalities. The history of aspirin spans ages and continents from Hippocrates' analgesic for women in labor to the rediscovery of the white willow bark by English country scholar Reverend Edward Stone. Bayer chemist Felix Hoffmann reinvented aspirin for his ailing father; suburban physician L.L. Craven pioneered the prophylactic antithrombotic uses of aspirin; and Sir John Vane elucidated aspirin's mechanism of action as the inhibition of prostaglandin synthetase. Heparin was discovered by McLean, working as a medical student in 1915 in search of a pure procoagulant in dog liver. His original impure material differed somewhat from today's heparin, but purified heparin was rapidly accepted for a myriad of clinical uses; to this day, diverse new properties of this complex glycosaminoglycan continue to be elucidated. The oral anticoagulants emerged from veterinary research in the 1920s on a hemorrhagic disorder afflicting cattle that consumed spoiled sweet clover hay. Several chance encounters led Karl Link and his University of Wisconsin team to the identification of dicumarol as the offending agent in 1939 and its widespread therapeutic use by Wright and others in the 1940s. Link later developed warfarin as a rodenticide, but its use in humans soon followed in the 1950s. Vitamin K was discovered in the 1930s; its involvement in the mechanism of the anticoagulant agents was not delineated until the 1970s. The intrinsic ability of clotted blood to liquify and the fibrinolytic properties of normal urine were noted in the 1800s. Tillett and Sherry's group stumbled on the fibrinolytic properties of streptokinase in the 1930s and pioneered the therapeutic use of streptokinase in the 1940s and of urokinase in the 1960s. Several teams found tissue-type plasminogen activator in various body sites beginning in the 1940s, leading to its cloning and widespread use in the 1980s; anisoylated plasminogen-streptokinase activator complex is an example of rational drug design. The discoverers of these diverse agents have not only provided physicians with a potent armamentarium of antithrombotic drugs but also helped elucidate much basic science and vividly demonstrated the merits of perseverance, independent thought, and adherance to the scientific method.

FIFRA Project Officers Manual

EPA Pesticide Factsheets

The FIFRA Project Officers Manual provides guidance to new as well as experienced project officers in the management of grants and cooperative agreements under the Federal Insecticide, Fungicide and Rodenticide Act.

FIFRA Scientific Advisory Panel

EPA Pesticide Factsheets

Experts on the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel provide independent scientific advice to the EPA on a wide range of health and safety issues related to pesticides.

PPIS Information and Report Samples

EPA Pesticide Factsheets

Technical information about the Pesticide Product Information System and its downloadable file formats, and sample reporting for Federal Insecticide Fungicide and Rodenticide Act (FIFRA) section 3 and section 24(c).

Disclosure of Reviews of Pesticide Test Data

EPA Pesticide Factsheets

This document describes a class determination that certain EPA-prepared reviews of data submitted under the Federal insecticide, Fungicide, and Rodenticide Act are not entitled to confidential treatment.

[Health risks from pest control products].

PubMed

Pieper, C; Holthenrich, D; Schneider, H

2014-05-01

According to European biocide legislation, pest control products require assessment and authorization by the responsible national or European authorities. Biocidal products can only be authorized if they have no unacceptable effects on human health. The health risk assessment performed for authorization comprises (a) the derivation of reference values for the active substances and substances of concern contained in the biocidal product and (b) an exposure assessment. These parameters are required for risk characterization. No unacceptable health risks are expected if the determined exposure is less than the relevant reference value. In addition, the toxicological information is used for classification of the biocidal product. The assessment may, where necessary, result in specific conditions for use or other restrictions aimed at minimizing risk. The risk to human health from pest control products is mainly based on the toxicological properties of their active substances. Commonly, the coformulants used in pest control products are of less concern than the active substances (e.g., food ingredients and animal feed products). For example, most rodenticides belong to the group of anticoagulants, which are also effective in humans. Regarding intoxications through insecticides, the group of pyrethroids is of particular importance. Fumigants containing metal phosphides, hydrogen cyanide, or sulfuryl difluoride are particularly toxic. This toxicity is linked to the high acute inhalation toxicity of the gaseous active substances themselves or, in the case of phosphides, of the released gas phosphane. The aim of health risk assessment for the authorization of biocidal products is to ensure their safe application for users and all other persons involved, assuming an adequate and label-compliant use.

Scientific Advisory Panel Report for Glyphosate Available

EPA Pesticide Factsheets

The Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) met December 13-16, 2016, to consider a set of scientific issues being evaluated by the Environmental Protection Agency

Why We Review Pesticides

EPA Pesticide Factsheets

As required by the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), EPA periodically reviews existing registered pesticides to ensure they can be used safely, without unreasonable risks to human health and the environment.

PPIS Download Product Information Data

EPA Pesticide Factsheets

Downloadable Pesticide Product Information System data for Federal Insecticide Fungicide and Rodenticide Act section 3 and section 24(c) (Special Local Need), vocabulary, and U.S. companies and organizations with EPA Company Numbers.

Registration Review Process

EPA Pesticide Factsheets

EPA will review each registered pesticide at least every 15 years to determine whether it continues to meet the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) standard for registration. There are currently 745 registration review cases.

Report on Minor Uses of Pesticides

EPA Pesticide Factsheets

This report on minor uses of pesticides was required by Section 31 of the Federal Insecticide, Fungicide and Rodenticide Act. It describes EPA's minor use activities and our partnerships with other federal agencies.

Differential antagonism of tetramethylenedisulfotetramine-induced seizures by agents acting at NMDA and GABA{sub A} receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shakarjian, Michael P., E-mail: michael_shakarjian@nymc.edu; Department of Medicine, Division of Pulmonary and Critical Care Medicine, UMDNJ–Robert Wood Johnson Medical School, Piscataway, NJ 08854; Velíšková, Jana, E-mail: jana_veliskova@nymc.edu

Tetramethylenedisulfotetramine (TMDT) is a highly lethal neuroactive rodenticide responsible for many accidental and intentional poisonings in mainland China. Ease of synthesis, water solubility, potency, and difficulty to treat make TMDT a potential weapon for terrorist activity. We characterized TMDT-induced convulsions and mortality in male C57BL/6 mice. TMDT (ip) produced a continuum of twitches, clonic, and tonic–clonic seizures decreasing in onset latency and increasing in severity with increasing dose; 0.4 mg/kg was 100% lethal. The NMDA antagonist, ketamine (35 mg/kg) injected ip immediately after the first TMDT-induced seizure, did not change number of tonic–clonic seizures or lethality, but increased the numbermore » of clonic seizures. Doubling the ketamine dose decreased tonic–clonic seizures and eliminated lethality through a 60 min observation period. Treating mice with another NMDA antagonist, MK-801, 0.5 or 1 mg/kg ip, showed similar effects as low and high doses of ketamine, respectively, and prevented lethality, converting status epilepticus EEG activity to isolated interictal discharges. Treatment with these agents 15 min prior to TMDT administration did not increase their effectiveness. Post-treatment with the GABA{sub A} receptor allosteric enhancer diazepam (5 mg/kg) greatly reduced seizure manifestations and prevented lethality 60 min post-TMDT, but ictal events were evident in EEG recordings and, hours post-treatment, mice experienced status epilepticus and died. Thus, TMDT is a highly potent and lethal convulsant for which single-dose benzodiazepine treatment is inadequate in managing electrographic seizures or lethality. Repeated benzodiazepine dosing or combined application of benzodiazepines and NMDA receptor antagonists is more likely to be effective in treating TMDT poisoning. -- Highlights: ► TMDT produces convulsions and lethality at low doses in mice. ► Diazepam pre- or post-treatments inhibit TMDT-induced convulsions and death. ► Ketamine and MK-801 display biphasic actions on TMDT seizures. ► Diazepam stops convulsions, but ictal EEG events persist to cause lethality hrs later. ► Diazepam repeat dose or paired with ketamine/MK-801 may more effectively block TMDT.« less

Pesticide Reregistration Performance Measures and Goals 1997-2008

EPA Pesticide Factsheets

Find past annual reports that were submitted, as required by the Federal Insecticide Fungicide and Rodenticide Act (as amended by FQPA), describing the agency's progress in meeting goals for reregistration and tolerance assessment.

Consent Agreement and Consent Order

EPA Pesticide Factsheets

Contains legal consent agreement and consent order for the assessment of a civil penality pursuant to Section 14(1) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), BioLab Inc., Conyers, GA, September 14, 1998.

Efficacy Testing of Pesticides used for Invertebrate Pests and Fire Ants

EPA Pesticide Factsheets

Event page for the upcoming Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) meeting on Efficacy Testing of Pesticides used for Invertebrate Pests and Fire Ants

Science Advisory Panel Meeting on PBPK Modeling Postponed

EPA Pesticide Factsheets

EPA is postponing the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) meeting scheduled for October 24-27, 2017 due to the unavailability of experts for the peer review panel.

[Strategies for sustainable management of commensal rodents. Definitions of control objectives at communal level].

PubMed

Plenge-Bönig, A; Schmolz, E

2014-05-01

The German Act on the Prevention and Control of Infectious Diseases in Man (Infektionsschutzgesetz, IfSG) provides a legal framework for activities and responsibilities concerning communal rodent control. However, actual governance of communal rodent control is relatively heterogeneous, as federal states (Bundesländer) have different or even no regulations for prevention and management of commensal rodent infestations (e.g. brown rats, roof rats and house mice). Control targets and control requirements are rarely precisely defined and often do not go beyond general measures and objectives. Although relevant regulations provide information about agreed preventive measures against rodents, the concept of sustainability is not expressed as such. A centrally managed database-supported municipal rodent control is a key factor for sustainability because it allows a systematic and analytical approach to identify and reduce rodent populations. The definition of control objectives and their establishment in legal decrees is mandatory for the implementation of a sustainable management strategy of rodent populations at a local level. Systematic recording of rodent infestations through municipal-operated monitoring provides the essential data foundation for a targeted rodent management which is already implemented in some German and European cities and nationwide in Denmark. A sustainable rodent management includes a more targeted rodenticide application which in the long-term will lead to an overall reduction of rodenticide use. Thus, the benefits of sustainable rodent management will be a reduction of rodenticide exposure to the environment, prevention of resistance and long-term economical savings.

ECOLOGICAL EFFECTS OF GENE FLOW.

EPA Science Inventory

The Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) and the Government Performance Results Act (GPRA, goal number four for Safe Communities), constitute the statutory authority and strategic framework respectively, for Agency research on non-target effects of pestici...

Botulism outbreak causes high mortality in Scottish cattle.

PubMed

2017-11-11

SAc C VS disease Surveillance report for july 2017 Botulism in finishing cattleSeasonal dermatitis in Cheviot ewes Streptococcus suis type 2 meningitis and septicaemia in pigletsRodenticide toxicity in chickens. British Veterinary Association.

Scientific Advisory Panel to Meet on Cancer Potential of Glyphosate

EPA Pesticide Factsheets

The Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) will meet October 18-21, 2016, to consider and review a set of scientific issues being evaluated by the regarding EPA's evaluation

Lupus anticoagulants and antiphospholipid antibodies

MedlinePlus

Blood clots - lupus anticoagulants; DVT - anticoagulants ... Most often, lupus anticoagulants and aPL are found in people with diseases such as systemic lupus erythematosus (SLE). Lupus anticoagulants and ...

Determining If Insect Repellent Skin Patch Products Must Be Registered Under FIFRA

EPA Pesticide Factsheets

Certain skin patch products that claim to repel insects are required to be registered under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), while others are exempt. Learn more about this issue.

FIFRA Peer Review: Proposed Risk Assessment Methods Process

EPA Pesticide Factsheets

From September 11-14, 2012, EPA participated in a Federal Insecticide, Fungicide and Rodenticide Act Scientific Advisory Panel (SAP) meeting on a proposed pollinator risk assessment framework for determining the potential risks of pesticides to honey bees.

Notification: National Pesticide Information Center Federal Insecticide, Fungicide, and Rodenticide Act Enforcement Referrals

EPA Pesticide Factsheets

Project #OPE-FY14-0035, March 21, 2014. The Office of Inspector General is starting preliminary research on the U.S. Environmental Protection Agency's oversight of the National Pesticide Information Center program.

Effects of tetramine used for rodent control in direct seeding of Douglas-fir.

Treesearch

Elmer W. Shaw

1953-01-01

Rodent control is one of the most critical problems in reforestation by direct seeding. Several different types of rodenticides, baits, and repellents have been developed, but none have been completely satisfactory.

Quantitative Analysis and Stability of the Rodenticide TETS ...

EPA Pesticide Factsheets

Journal Article The determination of the rodenticide tetramethylenedisulfotetramine (TETS) in drinking water is reportable through the use of automated sample preparation via solid phase extraction and detection using isotope dilution gas chromatography-mass spectrometry. The method was characterized over twenty-two analytical batches with quality control samples. Accuracies for low and high concentration quality control pools were 100 and 101%, respectively. The minimum reporting level (MRL) for TETS in this method is 0.50 ug/L. Five drinking waters representing a range of water quality parameters and disinfection practices were fortified with TETS at ten times the MRL and analyzed over a 28 day period to determine the stability of TETS in these waters. The amount of TETS measured in these samples averaged 100 ± 6% of the amount fortified suggesting that tap water samples may be held for up to 28 days prior to analysis.

Recovery of brodifacoum in vomitus following induction of emesis in dogs that had ingested rodenticide bait.

PubMed

Parton, K H; Willson, E K; Collett, M G; Booth, L H

2018-01-01

To assess the benefit of inducing emesis in dogs that have ingested rodenticide bait containing brodifacoum (BDF), by determining the amount of BDF in bait recovered from the vomitus relative to the estimated amount consumed. Between 2014 and 2015 samples of vomitus from seven dogs that ingested rodenticide baits containing BDF were submitted by veterinarians in New Zealand. All seven dogs had been given apomorphine by the veterinarian and vomited within 1 hour of ingesting the bait. Some or all of the bait particles were retrieved from each sample and were analysed for concentrations of BDF using HPLC. Based on estimations of the mass of bait consumed, the concentration of BDF stated on the product label, and the estimated mass of bait in the vomitus of each dog, the amount of BDF in the vomited bait was calculated as a percentage of the amount ingested. For five dogs an estimation of the mass of bait ingested was provided by the submitting veterinarian. For these dogs the estimated percentage of BDF in the bait retrieved from the vomitus was between 10-77%. All dogs were well after discharge but only one dog returned for further testing. This dog had a normal prothrombin time 3 days after ingestion. The induction of emesis within 1 hour of ingestion can be a useful tool in reducing the exposure of dogs to a toxic dose of BDF. The BDF was not fully absorbed within 1 hour of ingestion suggesting that the early induction of emesis can remove bait containing BDF before it can be fully absorbed.

Effect of sodium citrate based anticoagulants on the growth activity of malaria parasites.

PubMed

Liu, Zhong-xiang; Wang, Xian-feng; Li, Shu-mei; Li, Xun; Xue, Cai-fang; Miao, Jun

2004-12-01

To study the effect of anticoagulants based on sodium citrate on the growth activity of malaria parasites. The parasites were treated with 3 anticoagulants (ACD, CD and SC), respectively, and the parasitemia was determined to measure the effect of the anticoagulants on the growth of the parasites. Unsynchronized Plasmodium falciparum was treated with the anticoagulants at different concentrations for 3 h at 37 degrees C. Treated erythrocytes were mixed with normal parasites or treated parasites with normal erythrocytes, which was followed by parasitemia determination of the two cultures to determine the cell target of the anticoagulants. Stage-synchronized parasites (ring, trophozoite and schizont) were treated as above to investigate the stage target. P. berghei was also treated with anticoagulants and inoculated in mice to detect the effect of anticoagulants on the animal malaria parasite by counting the parasitemia. All 3 anticoagulants inhibited falciparum parasite growth and ACD had the strongest potency. The treatments of the erythrocyte and the parasite with anticoagulants respectively showed that the anticoagulants targeted the parasites rather than normal erythrocytes. Stage-synchronized parasite treatment suggested anticoagulants primarily inhibited schizonts. The effect of anticoagulants on P. berghei was similar to that on P. falciparum. ACD showed the most significant inhibitive effect on the growth of malaria parasites and SC was the best anticoagulant based on sodium citrate for malarial experiments.

Mitochondrial DNA phylogeography of the Norway rat.

PubMed

Song, Ying; Lan, Zhenjiang; Kohn, Michael H

2014-01-01

Central Eastern Asia, foremost the area bordering northern China and Mongolia, has been thought to be the geographic region where Norway rats (Rattus norvegicus) have originated. However recent fossil analyses pointed to their origin in southern China. Moreover, whereas analyses of fossils dated the species' origin as ∼ 1.2-1.6 million years ago (Mya), molecular analyses yielded ∼ 0.5-2.9 Mya. Here, to study the geographic origin of the Norway rat and its spread across the globe we analyzed new and all published mitochondrial DNA cytochrome-b (cyt-b; N = 156) and D-loop (N = 212) sequences representing wild rats from four continents and select inbred strains. Our results are consistent with an origin of the Norway rat in southern China ∼ 1.3 Mya, subsequent prehistoric differentiation and spread in China and Asia from an initially weakly structured ancestral population, followed by further spread and differentiation across the globe during historic times. The recent spreading occurred mostly from derived European populations rather than from archaic Asian populations. We trace laboratory strains to wild lineages from Europe and North America and these represent a subset of the diversity of the rat; leaving Asian lineages largely untapped as a resource for biomedical models. By studying rats from Europe we made the observation that mtDNA diversity cannot be interpreted without consideration of pest control and, possibly, the evolution of rodenticide resistance. However, demographic models explored by forward-time simulations cannot fully explain the low mtDNA diversity of European rats and lack of haplotype sharing with their source from Asia. Comprehensive nuclear marker analyses of a larger sample of Norway rats representing the world are needed to better resolve the evolutionary history of wild rats and of laboratory rats, as well as to better understand the evolution of anticoagulant resistance.

Pesticide Dashboard Help | ECHO | US EPA

EPA Pesticide Factsheets

The dashboards found on the Enforcement and Compliance History Online (ECHO) website are specialized to track both facility and agency performance as they relate to compliance with and enforcement of environmental standards under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).

Notification: Preliminary Research on the Adequacy of EPA's Oversight of State FIFRA Programs

EPA Pesticide Factsheets

Project #OPE-FY14-4013, November 06, 2013. The EPA OIG plans to begin preliminary research on the adequacy of the EPA’s oversight of states’ Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) programs.

40 CFR 26.1102 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... performance of routine physical or psychological examinations or tests. (i) Research involving intentional... Requirements for Third-Party Human Research for Pesticides Involving Intentional Exposure of Non-pregnant, Non... Insecticide, Fungicide, and Rodenticide Act, section 2(u)). (d) Research means a systematic investigation...

Consideration of Prions as a Pest under FIFRA

EPA Pesticide Factsheets

This is the record of decision regarding prions should be considered to be a “pest” the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended. It includes information about EPA regulation of pesticides based on this decision.

Anticoagulation and high dose liver radiation. A preliminary report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lightdale, C.J.; Wasser, J.; Coleman, M.

Two groups of patients were observed for evidence of acute radiation hepatitis during high dose radiation to the liver. The first group of 18 patients with metastatic liver disease received an average of 4,050 rad to the whole liver. Half received anticoagulation with warfarin. One patient on anticoagulation developed evidence of acute radiation hepatitis while 2 patients did so without anticoagulation. Eleven patients with Hodgkin's disease received 4,000 rad to the left lobe of the liver during extended field radiation. Four of these 11 patients were anticoagulated to therapeutic range. Only one of the fully anticoagulated patients showed changes onmore » liver scan consistent with radiation hepatitis whereas three did so without anticoagulation. No serious sequelae from anticoagulation occurred in either group. These preliminary data suggest that anticoagulation may be safely administered with high dose hepatic radiation and that further trials with anticoagulation are warranted.« less

50 CFR 402.43 - Interagency exchanges of information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S. Environmental Protection Agency Under the Federal Insecticide, Fungicide and Rodenticide Act § 402.43...

50 CFR 402.43 - Interagency exchanges of information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S. Environmental Protection Agency Under the Federal Insecticide, Fungicide and Rodenticide Act § 402.43...

50 CFR 402.43 - Interagency exchanges of information.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S. Environmental Protection Agency Under the Federal Insecticide, Fungicide and Rodenticide Act § 402.43...

50 CFR 402.43 - Interagency exchanges of information.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S. Environmental Protection Agency Under the Federal Insecticide, Fungicide and Rodenticide Act § 402.43...

50 CFR 402.43 - Interagency exchanges of information.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S. Environmental Protection Agency Under the Federal Insecticide, Fungicide and Rodenticide Act § 402.43...

Ubertool: Web Application for Ecological Risk Assessment of Pesticides

EPA Science Inventory

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) the U.S. Environmental Protection Agency (EPA) must regulate (license) pesticides before they become commercially available to ensure they will not cause unreasonable adverse effects on human health or the envi...

40 CFR 35.250 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL... Cooperative Agreements to States (as defined in section 2 of Federal Insecticide, Fungicide, and Rodenticide... Cooperative Agreements are awarded to assist States to develop and implement pesticide programs, including...

40 CFR 35.250 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL... Cooperative Agreements to States (as defined in section 2 of Federal Insecticide, Fungicide, and Rodenticide... Cooperative Agreements are awarded to assist States to develop and implement pesticide programs, including...

40 CFR 35.650 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL... Implementation cooperative agreements to Tribes and Intertribal Consortia under section 23(a)(1) of the Federal Insecticide, Fungicide, and Rodenticide Act. (b) Purpose of program. Cooperative agreements are awarded to...

40 CFR 35.650 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL... Implementation cooperative agreements to Tribes and Intertribal Consortia under section 23(a)(1) of the Federal Insecticide, Fungicide, and Rodenticide Act. (b) Purpose of program. Cooperative agreements are awarded to...

40 CFR 164.102 - Appeals from accelerated decisions.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... 164.102 Section 164.102 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... of the submission of briefs, but the Environmental Appeals Board may allow additional briefs and oral...

40 CFR 164.102 - Appeals from accelerated decisions.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... 164.102 Section 164.102 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... of the submission of briefs, but the Environmental Appeals Board may allow additional briefs and oral...

The Importance of Soil Protein Fate to PIP Crop Registration

EPA Science Inventory

Plant Incorporated Protectant (PIP) crops are registered under the authority of the Federal Insecticide Fungicide and Rodenticide Act (FIFRA) and as part of this registration certain environmental fate information is required to properly judge the environmental compatibility of n...

Influence of novel oral anticoagulants on anticoagulation care management.

PubMed

Janzic, Andrej; Kos, Mitja

2017-09-01

Anticoagulation treatment was recently improved by the introduction of novel oral anticoagulants (NOACs). Using a combination of qualitative and quantitative methods, this study explores the effects of the introduction of NOACs on anticoagulation care in Slovenia. Face-to-face interviews with key stakeholders revealed evolvement and challenges of anticoagulation care from different perspectives. Obtained information was further explored through the analysis of nationwide data of drug prescriptions and realization of health care services. Simplified management of anticoagulation treatment with NOACs and their high penetration expanded the capacity of anticoagulation clinics, and consequentially the treated population increased by more than 50 % in the last 5 years. The main challenge concerned the expenditures for medicines, which increased approximately 10 times in just a few years. At the same time, the anticoagulation clinics and their core organisation were not affected, which is not expected to change, since they are vital in delivering high-quality care.

50 CFR 402.47 - Special consultation procedures for complex FIFRA actions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations... Rodenticide Act § 402.47 Special consultation procedures for complex FIFRA actions. (a) Successive effects...

50 CFR 402.47 - Special consultation procedures for complex FIFRA actions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations... Rodenticide Act § 402.47 Special consultation procedures for complex FIFRA actions. (a) Successive effects...

50 CFR 402.47 - Special consultation procedures for complex FIFRA actions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations... Rodenticide Act § 402.47 Special consultation procedures for complex FIFRA actions. (a) Successive effects...

50 CFR 402.42 - Scope and applicability.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S. Environmental Protection Agency Under the Federal Insecticide, Fungicide and Rodenticide Act § 402.42 Scope and...

50 CFR 402.42 - Scope and applicability.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S. Environmental Protection Agency Under the Federal Insecticide, Fungicide and Rodenticide Act § 402.42 Scope and...

50 CFR 402.47 - Special consultation procedures for complex FIFRA actions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations... Rodenticide Act § 402.47 Special consultation procedures for complex FIFRA actions. (a) Successive effects...

50 CFR 402.47 - Special consultation procedures for complex FIFRA actions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations... Rodenticide Act § 402.47 Special consultation procedures for complex FIFRA actions. (a) Successive effects...

50 CFR 402.42 - Scope and applicability.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S. Environmental Protection Agency Under the Federal Insecticide, Fungicide and Rodenticide Act § 402.42 Scope and...

50 CFR 402.42 - Scope and applicability.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S. Environmental Protection Agency Under the Federal Insecticide, Fungicide and Rodenticide Act § 402.42 Scope and...

50 CFR 402.42 - Scope and applicability.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations Governing Actions by the U.S. Environmental Protection Agency Under the Federal Insecticide, Fungicide and Rodenticide Act § 402.42 Scope and...

Back-end Science Model Integration for Ecological Risk Assessment

EPA Science Inventory

The U.S. Environmental Protection Agency (USEPA) relies on a number of ecological risk assessment models that have been developed over 30-plus years of regulating pesticide exposure and risks under Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Endangered Spe...

Back-end Science Model Integration for Ecological Risk Assessment.

EPA Science Inventory

The U.S. Environmental Protection Agency (USEPA) relies on a number of ecological risk assessment models that have been developed over 30-plus years of regulating pesticide exposure and risks under Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Endangered Spe...

ASSESSMENT OF CHLORPYRIFOS EXPOSURE BY PASSIVE DOSIMETRY AND BIOMONITORING IN PESTICIDE WORKERS

EPA Science Inventory

Under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), the U.S. Environmental Protection Agency (EPA) has the authority to regulate the use of pesticides to prevent unreasonable adverse human health effects associated with pesticide exposure. Accordingly, the EPA...

Cheminformatics and Computational Chemistry: A Powerful Combination for the Encoding of Process Science

EPA Science Inventory

The registration of new chemicals under the Toxicological Substances Control Act (TSCA) and new pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) requires knowledge of the process science underlying the transformation of organic chemicals in natural...

40 CFR 35.230 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL... Agreements to States (as defined in section 2 of Federal Insecticide, Fungicide, and Rodenticide Act) under... program regulations are at 40 CFR parts 150 through 189 and 19 CFR part 12. ...

40 CFR 35.230 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL... Agreements to States (as defined in section 2 of Federal Insecticide, Fungicide, and Rodenticide Act) under... program regulations are at 40 CFR parts 150 through 189 and 19 CFR part 12. ...

The effects of glyphosate and aminopyralid on an artifical plant communities

EPA Science Inventory

The US EPA has responsibility for registration of pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). The potential adverse effects of pesticides to nontarget terrestrial plant communities are a concern that must be addressed in the pesticide regist...

The effects of low levels of herbicides on simple plant communities

EPA Science Inventory

In the United States, the US Environmental Protection Agency has the responsibility for the registration of pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act. Prior to registration applicants must demonstrate that their product will not adversely affect hu...

40 CFR 164.111 - Procedure for disposition of motions.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... 164.111 Section 164.111 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... thereafter, the Environmental Appeals Board shall announce its decision whether to grant or to deny the...

40 CFR 164.22 - Contents of document setting forth objections.

Code of Federal Regulations, 2011 CFR

2011-07-01

... objections. 164.22 Section 164.22 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... registration, or change the classification of a pesticide, shall clearly and concisely set forth such...

40 CFR 164.103 - Final decision or order on appeal or review.

Code of Federal Regulations, 2011 CFR

2011-07-01

... review. 164.103 Section 164.103 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... of an accelerated decision, unless otherwise stipulated by the parties, the Environmental Appeals...

40 CFR 164.103 - Final decision or order on appeal or review.

Code of Federal Regulations, 2010 CFR

2010-07-01

... review. 164.103 Section 164.103 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... of an accelerated decision, unless otherwise stipulated by the parties, the Environmental Appeals...

40 CFR 164.111 - Procedure for disposition of motions.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... 164.111 Section 164.111 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... thereafter, the Environmental Appeals Board shall announce its decision whether to grant or to deny the...

40 CFR 164.22 - Contents of document setting forth objections.

Code of Federal Regulations, 2010 CFR

2010-07-01

... objections. 164.22 Section 164.22 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... registration, or change the classification of a pesticide, shall clearly and concisely set forth such...

Notification: Evaluation of EPA’s Regional Negotiated Commitments with States for FIFRA Compliance Inspections

EPA Pesticide Factsheets

Project No. OPE-FY15-0022, March 23, 2015. The EPA OIG plans to begin preliminary research on the EPA’s regional negotiated commitments with states for Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) compliance inspections.

A prospective randomized open-label crossover trial of regional citrate anticoagulation vs. anticoagulation free liver dialysis by the Molecular Adsorbents Recirculating System

PubMed Central

2012-01-01

Introduction The Molecular Adsorbent Recycling System (MARS) is used to treat patients with liver failure. Observational data suggest that citrate anticoagulation during MARS is feasible. Comparative studies on the optimal anticoagulation regimen during MARS are lacking. The aim of the current study was to evaluate two heparin-free anticoagulation regimens. Methods We performed a prospective randomized open-label crossover study of regional citrate anticoagulation against no anticoagulation. Ten patients (age 55 ± 11 years) with liver failure undergoing MARS treatment were included. The primary endpoint was completion of MARS sessions. Secondary endpoints included treatment efficacy and safety. Longevity of MARS treatment was plotted as a Kaplan-Meier estimate. Fisher's exact test was used for contingency table analysis. Results Of a total of 27 6-hour sessions, four sessions had to be terminated prematurely, three due to occlusive clotting of the extracorporeal circuit and one due to uncontrollable bleeding from the vascular access site. All four events occurred in the group without anticoagulation. Between group comparison demonstrated citrate anticoagulation to significantly increase the likelihood of completed MARS treatment (Fisher's exact test, P 0.04). This translates into higher bilirubin reduction ratios when citrate was applied (reduction ratio 0.25 vs. 0.15, P 0.02). Systemic ionized calcium concentrations were significantly reduced during citrate anticoagulation (P < 0.001) but remained within a safe range. We observed no major adverse events. Conclusions Regional citrate anticoagulation in patients with liver failure is feasible. Citrate anticoagulation provides superior patency of the extracorporeal circuit. Avoidance of anticoagulation during MARS results in significant loss of treatment efficacy, due to treatment downtime. Additional studies are required to identify the optimal anticoagulation regimen for extracorporeal circulation in patients with liver failure. PMID:22305273

Diagnostic Error of a Patient with Combined Inherited Factor VII and Factor X Deficiency due to Accidental Ingestion of a Diphacinone Rodenticide.

PubMed

Li, Min; Jin, Yanhui; Wang, Mingshan; Xie, Yaosheng; Ding, Hongxiang

2016-11-01

To explore the characteristics of laboratory examination and confirm the diagnosis of a patient with combined inherited FVII and FX deficiency after he ingested diphacinone rodenticide accidentally. The coagulant parameter screening tests and coagulation factor activities were tested many times in the patient due to accidental ingestion of a diphacinone rodenticide. After the patient was treated for more than one year, gene analysis of correlated coagulation factors was analyzed in the patient and other family members by DNA direct sequencing. 106 persons were selected as controls from routine health examinations. After the patient was admitted to hospital, routine coagulation screening tests revealed the prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) and low levels of vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) activity, which was 102.4 seconds, 88.5 seconds, 7%, 3%, 8%, and 2%, respectively. During more than one year of treatment, the value of PT and APTT still showed significantly prolonged activity and FVII and FX activity levels were about 5%. While FII and FIX activity levels were in the normal range after 12 weeks of treatment. Two homozygous mutations, g.11267C>T of F7 gene resulting in the substitution Arg277Cys and g.28139G>T of F10 gene leading to the substitution Val384Phe, were identified in the patient. The patient's parents and sister was heterozygous for Arg277Cys and Val384Phe mutations. FVII and FX antigen levels in the patient were 7% and 30%, respectively. There were many similarities in the characteristics of laboratory examination between combined inherited FVII and FX deficiency and acquired vitamin K deficiency. The best way to identify them was gene analysis.

Time trends in intracranial bleeding associated with direct oral anticoagulants: a 5-year cohort study

PubMed Central

Hogg, Kerstin; Bahl, Bharat; Latrous, Meriem; Scaffidi Argentina, Sarina; Thompson, Jesse; Chatha, Aasil Ayyaz; Castellucci, Lana; Stiell, Ian G.

2015-01-01

Background: Over the past 5 years, dabigatran, rivaroxaban and apixaban were approved for stroke prevention. Phase III studies have shown a lower risk of intracranial bleeding with these direct oral anticoagulants than with warfarin; however, there is a lack of real-life data to validate this. We analyzed time trends in atraumatic intracranial bleeding from 2009 to 2013 among patients prescribed oral anticoagulants and those not prescribed oral anticoagulants. Methods: We used ICD-10-CA (enhanced Canadian version of the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) codes to identify all patients with atraumatic intracranial bleeding who presented to our neurosurgical centre (serving a population of more than 1.2 million). Trained researchers extracted data on anticoagulant medications used in the week before diagnosis of the intracranial bleed. Provincial prescription data for oral anticoagulants were obtained from IMS Brogan CompuScript Market Dynamics. The primary outcome was the time trend in incident intracranial bleeds associated with oral anticoagulation during the period 2009-2013. The secondary outcomes were the time trend in intracranial bleeds not associated with oral anticoagulation and the provincial prescribing patterns for oral anticoagulants during the same period. Results: A total of 2050 patients presented with atraumatic intracranial bleeds during the study period. Of the 371 (18%) prescribed an anticoagulant in the week before presentation, 335 were prescribed an oral anticoagulant. There was an increasing time trend in intracranial bleeding associated with oral anticoagulants (p = 0.009; 6 additional events per year) and in intracranial bleeding not associated with oral anticoagulation (p = 0.06). During 2013, prescriptions for warfarin decreased to 70% of all oral anticoagulant prescriptions in the province, whereas those for dabigatran and rivaroxaban increased to 17% and 12%, respectively. Interpretation: We observed increasing time trends in intracranial bleeding, both associated with and not associated with oral anticoagulants, over the study period. Although aggregate provincial data showed increased prescribing of oral anticoagulants, other more likely explanations for our findings include an aging population or increasing frailty. PMID:26770966

Practical management of anticoagulation in patients with atrial fibrillation.

PubMed

Kovacs, Richard J; Flaker, Greg C; Saxonhouse, Sherry J; Doherty, John U; Birtcher, Kim K; Cuker, Adam; Davidson, Bruce L; Giugliano, Robert P; Granger, Christopher B; Jaffer, Amir K; Mehta, Bella H; Nutescu, Edith; Williams, Kim A

2015-04-07

Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, management of major and minor bleeding, and treatment of special populations. The attendees continued to work toward consensus on these topics, and present the key findings of this roundtable in a state-of- the-art review focusing on the practical aspects of anticoagulation care for the patient with atrial fibrillation. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

50 CFR 402.48 - Conference on proposed species or proposed critical habitat.

Code of Federal Regulations, 2014 CFR

2014-10-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations... Rodenticide Act § 402.48 Conference on proposed species or proposed critical habitat. EPA may employ the...

50 CFR 402.48 - Conference on proposed species or proposed critical habitat.

Code of Federal Regulations, 2012 CFR

2012-10-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations... Rodenticide Act § 402.48 Conference on proposed species or proposed critical habitat. EPA may employ the...

50 CFR 402.48 - Conference on proposed species or proposed critical habitat.

Code of Federal Regulations, 2013 CFR

2013-10-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE); ENDANGERED SPECIES COMMITTEE REGULATIONS SUBCHAPTER A INTERAGENCY COOPERATION-ENDANGERED SPECIES ACT OF 1973, AS AMENDED Counterpart Regulations... Rodenticide Act § 402.48 Conference on proposed species or proposed critical habitat. EPA may employ the...

An Integrated Web-Based Assessment Tool for Assessing Pesticide Exposure and Risks

EPA Science Inventory

Background/Question/Methods We have created an integrated web-based tool designed to estimate exposure doses and ecological risks under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Endangered Species Act. This involved combining a number of disparat...

ASSESSING CONTAMINANT SENSITIVITY OF ENDANGERED AND THREATENED SPECIES: TOXICANT CLASSES

EPA Science Inventory

Under the Federal Insecticide, Fungicide and Rodenticide Act, the Toxic Substances Control Act and the Clean Water Act, the U.S. Environmental Protection Agency (EPA) is charged with determining if the manufacture, use, or disposal of a chemical will present an unreasonable risk ...

Notification: Evaluation of the Adequacy of EPA’s Oversight of State Federal Insecticide, Fungicide, and Rodenticide Act Programs

EPA Pesticide Factsheets

Project #OPE-FY14-0007, June 19, 2014. Our updated objective is to determine how the EPA's state oversight ensures the quality of state-performed Worker Protection Standard inspections and Certification and Training inspections.

PRN 75-5: Unacceptable Use of the Word Chlorine in the Name and Labeling of Pesticides

EPA Pesticide Factsheets

Use of the word CHLORINE on labels other than in products containing liquified chlorine under pressure has been determined to be in violation of Section 2(q)(l)(A) of the Federal Insecticide, Fungicide, and Rodenticide Act.

EPA Accepting Public Comments on Nominees for the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP)

EPA Pesticide Factsheets

FRN professional affiliations of recent nominees by the National Institutes of Health and the National Science Foundation for service on the FIFRA Scientific Advisory Panel established under section 25(d) of the FIFRA

21 CFR 226.20 - Buildings.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Buildings. 226.20 Section 226.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL... insecticides, fungicides, rodenticides, or other pesticides or their components unless such materials are...

40 CFR 164.122 - Final order and order of suspension.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... 164.122 Section 164.122 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... Environmental Appeals Board shall issue a final decision and order. Such final order may accept or reject in...

40 CFR 164.122 - Final order and order of suspension.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... 164.122 Section 164.122 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... Environmental Appeals Board shall issue a final decision and order. Such final order may accept or reject in...

Notification: Evaluation of EPA’s Federal Insecticide, Fungicide, and Rodenticide Act Section 18 Emergency Exemptions

EPA Pesticide Factsheets

Project #OPE-FY17-0024, August 21, 2017. The EPA OIG plans to begin preliminary research on the emergency exemption process used by the EPA’s Office of Chemical Safety and Pollution Prevention’s Office of Pesticide Programs.

A bill to amend the Federal Insecticide, Fungicide, and Rodenticide Act to improve the use of certain registered pesticides.

THOMAS, 112th Congress

Sen. Roberts, Pat [R-KS

2011-04-04

Senate - 04/04/2011 Read twice and referred to the Committee on Agriculture, Nutrition, and Forestry. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

A bill to amend the Federal Insecticide, Fungicide, and Rodenticide Act to improve the use of certain registered pesticides.

THOMAS, 113th Congress

Sen. Roberts, Pat [R-KS

2013-01-29

Senate - 01/29/2013 Read twice and referred to the Committee on Agriculture, Nutrition, and Forestry. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

A bill to amend the Federal Insecticide, Fungicide, and Rodenticide Act to improve the use of certain registered pesticides.

THOMAS, 111th Congress

Sen. Lincoln, Blanche L. [D-AR

2010-08-05

Senate - 08/05/2010 Read twice and referred to the Committee on Agriculture, Nutrition, and Forestry. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

LARGE AREA MONITORING FOR PESTICIDAL TRANSGENIC CROPS: HOW SPECTRAL IMAGING MAY PLAY A ROLE

EPA Science Inventory

Crops genetically engineered to contain a bacterial gene that expresses an insecticidal protein from Bacillus thuringiensis are regulated by EPA under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA). EPA has declared crops containing transgenic pesticidal traits to...

Untested pesticide mitigation requirements: ecological, agricultural, and legal implications

USGS Publications Warehouse

Vyas, Nimish B.

2013-01-01

Every pesticide sold in the United States must have a U.S. Environmental Agency approved label on its container. The label provides directions for the pesticide’s use and is legally enforceable under the Federal Insecticide, Fungicide and Rodenticide Act. For a pesticide with high ecological risks, mitigation statements may be included on the label to reduce the pesticide’s risks and to support its registration. Many mitigation mandates are easy to implement and are effective, however, at times, well-intentioned but novel and untested mitigation requirements, though theoretically sound, may not be perceived by the pesticide users to be practical under operational settings. Courts of law recognize the pesticide label as a legal document, therefore it is imperative that the label mitigation mandates be achievable. I use the rodenticide Rozol label to illustrate how an untested risk mitigation mandate may be considered too burdensome by pesticide users whereby the mitigation action may not be implemented in the field, resulting in label violation and unreasonable risks to the environment.

Anticoagulant Medicine: Potential for Drug-Food Interactions

MedlinePlus

... Medications Anticoagulants and Drug-Food Interactions Anticoagulants and Drug-Food Interactions Make an Appointment Ask a Question ... care provider before making the change. Anticoagulants and Medicine There are many medicines that can interact with ...

The mythology of anticoagulation therapy interruption for dental surgery.

PubMed

Wahl, Michael J

2018-01-01

Continuous anticoagulation therapy is used to prevent heart attacks, strokes, and other embolic complications. When patients receiving anticoagulation therapy undergo dental surgery, a decision must be made about whether to continue anticoagulation therapy and risk bleeding complications or briefly interrupt anticoagulation therapy and increase the risk of developing embolic complications. Results from decades of studies of thousands of dental patients receiving anticoagulation therapy reveal that bleeding complications requiring more than local measures for hemostasis have been rare and never fatal. However, embolic complications (some of which were fatal and others possibly permanently debilitating) sometimes have occurred in patients whose anticoagulation therapy was interrupted for dental procedures. Although there is now virtually universal consensus among national medical and dental groups and other experts that anticoagulation therapy should not be interrupted for most dental surgery, there are still some arguments made supporting anticoagulation therapy interruption. An analysis of these arguments shows them to be based on a collection of myths and half-truths rather than on logical scientific conclusions. The time has come to stop anticoagulation therapy interruption for dental procedures. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

Postpartum wound and bleeding complications in women who received peripartum anticoagulation.

PubMed

Limmer, Jane S; Grotegut, Chad A; Thames, Elizabeth; Dotters-Katz, Sarah K; Brancazio, Leo R; James, Andra H

2013-07-01

The objective of this study was to compare wound and bleeding complications between women who received anticoagulation after cesarean delivery due to history of prior venous thromboembolic disease, arterial disease, or being a thrombophilia carrier with adverse pregnancy outcome, to women not receiving anticoagulation. Women in the Duke Thrombosis Center Registry who underwent cesarean delivery during 2003-2011 and received postpartum anticoagulation (anticoagulation group, n=77), were compared with a subset of women who delivered during the same time period, but did not receive anticoagulation (no anticoagulation group, n=77). The no anticoagulation group comprised women who were matched to the anticoagulation group by age, body mass index, type of cesarean (no labor vs. labor), and date of delivery. Bleeding and wound complications were compared between the two groups. A multivariable logistic regression model was constructed to determine if anticoagulation was an independent predictor of wound complication. Women who received anticoagulation during pregnancy had a greater incidence of wound complications compared to those who did not (30% vs. 8%, p<0.001). Using multivariable logistic regression, while controlling for race, diabetes, chorioamnionitis, and aspirin use, anticoagulation predicted the development of any wound complication (OR 5.8, 95% CI 2.2, 17.6), but there were no differences in the mean estimated blood loss at delivery (782 vs. 778 ml, p=0.91), change in postpartum hematocrit (5.4 vs. 5.2%, p=0.772), or percent of women receiving blood products (6.5 vs. 1.3%, p=0.209) between the two groups. Anticoagulation following cesarean delivery is associated with an increased risk of post-cesarean wound complications, but not other postpartum bleeding complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Areas of improvement in anticoagulant safety. Data from the CACAO study, a cohort in general practice

PubMed Central

Cogneau, Joël; Gaboreau, Yoann; Abenhaïm, Nathan; Bayen, Marc; Calafiore, Matthieu; Guichard, Claude; Jacquet, Jean-Pierre; Lacoin, François; Bertoletti, Laurent

2017-01-01

Background Real-world studies on anticoagulants are mostly performed on health insurance databases, limited to reported events, and sometimes far from every-day issues in family practice. We assess the presence of data for safe monitoring of oral anticoagulants in general practice, and compare patients’ knowledge of taking an anticoagulant between vitamin K antagonists (VKA) and direct anticoagulants (DOAC), and the general practitioner’s perception of their adherence to anticoagulation. Methods The CACAO study is a national cohort study, conducted by general practitioners on ambulatory patients under oral anticoagulant. In the first phase, investigators provided safety data available from medical records at inclusion. They also evaluated patients’ knowledge about anticoagulation and graded their perception of patients’ adherence. Results Between April and December 2014, 463 general practitioners included 7154 patients. Renal and hepatic function tests were respectively unavailable in 109 (7.5%) and 359 (24.7%) DOAC patients. Among patients with atrial fibrillation, 345 patients (6.9%) had a questionable indication of anticoagulant (CHA2DS2-Vasc<2). One hundred and thirty-three VKA patients (2.3%) and 70 DOAC patients (4.9%) answered they took no anticoagulant (p<0.0001). According to general practitioners’ perception, 430 patients (6.1%) were classified as “not very” or “not adherent”, with no difference between groups. Conclusions Our results highlight the efforts needed to improve anticoagulant safety in daily practice: decreasing the rate of unknown biological data in patients with DOACs or the rate of patients with VKA with no strong indication of anticoagulation, and improving patient knowledge with regard to their anticoagulant. Patients’ adherence seems highly over-estimated by the general practitioners. Clinical trial registration ClinicalTrials.gov NCT02376777 PMID:28384199

Diet as prophylaxis and treatment for venous thromboembolism?

PubMed Central

2010-01-01

Background Both prophylaxis and treatment of venous thromboembolism (VTE: deep venous thrombosis (DVT) and pulmonary emboli (PE)) with anticoagulants are associated with significant risks of major and fatal hemorrhage. Anticoagulation treatment of VTE has been the standard of care in the USA since before 1962 when the U.S. Food and Drug Administration began requiring randomized controlled clinical trials (RCTs) showing efficacy, so efficacy trials were never required for FDA approval. In clinical trials of 'high VTE risk' surgical patients before the 1980s, anticoagulant prophylaxis was clearly beneficial (fatal pulmonary emboli (FPE) without anticoagulants = 0.99%, FPE with anticoagulants = 0.31%). However, observational studies and RCTs of 'high VTE risk' surgical patients from the 1980s until 2010 show that FPE deaths without anticoagulants are about one-fourth the rate that occurs during prophylaxis with anticoagulants (FPE without anticoagulants = 0.023%, FPE while receiving anticoagulant prophylaxis = 0.10%). Additionally, an FPE rate of about 0.012% (35/28,400) in patients receiving prophylactic anticoagulants can be attributed to 'rebound hypercoagulation' in the two months after stopping anticoagulants. Alternatives to anticoagulant prophylaxis should be explored. Methods and Findings The literature concerning dietary influences on VTE incidence was reviewed. Hypotheses concerning the etiology of VTE were critiqued in relationship to the rationale for dietary versus anticoagulant approaches to prophylaxis and treatment. Epidemiological evidence suggests that a diet with ample fruits and vegetables and little meat may substantially reduce the risk of VTE; vegetarian, vegan, or Mediterranean diets favorably affect serum markers of hemostasis and inflammation. The valve cusp hypoxia hypothesis of DVT/VTE etiology is consistent with the development of VTE being affected directly or indirectly by diet. However, it is less consistent with the rationale of using anticoagulants as VTE prophylaxis. For both prophylaxis and treatment of VTE, we propose RCTs comparing standard anticoagulation with low VTE risk diets, and we discuss the statistical considerations for an example of such a trial. Conclusions Because of (a) the risks of biochemical anticoagulation as anti-VTE prophylaxis or treatment, (b) the lack of placebo-controlled efficacy data supporting anticoagulant treatment of VTE, (c) dramatically reduced hospital-acquired FPE incidence in surgical patients without anticoagulant prophylaxis from 1980 - 2010 relative to the 1960s and 1970s, and (d) evidence that VTE incidence and outcomes may be influenced by diet, randomized controlled non-inferiority clinical trials are proposed to compare standard anticoagulant treatment with potentially low VTE risk diets. We call upon the U. S. National Institutes of Health and the U.K. National Institute for Health and Clinical Excellence to design and fund those trials. PMID:20701748

Anticoagulated patient's perception of their illness, their beliefs about the anticoagulant therapy prescribed and the relationship with adherence: impact of novel oral anticoagulant therapy - study protocol for The Switching Study: a prospective cohort study.

PubMed

Auyeung, Vivian; Patel, Jignesh P; Abdou, John K; Vadher, Bipin; Bonner, Lynda; Brown, Alison; Roberts, Lara N; Patel, Raj K; Arya, Roopen

2016-01-01

Anticoagulant therapy is prescribed for millions of patients worldwide for the prevention and treatment of both arterial and venous thrombosis. Historically, only vitamin K antagonists have been available for clinicians to prescribe. The anticoagulation landscape is changing. The recent availability of the novel oral anticoagulants overcome many of the disadvantages associated with vitamin K antagonists. However the lack of formal monitoring and clinic follow-up is a concern for clinicians, as medication adherence is being assumed, which is known to decline in patients prescribed medications for chronic conditions. The switching study is a programme of work investigating the association between medication adherence and patient's beliefs about anticoagulation therapy (warfarin and subsequently novel oral anticoagulants), together with beliefs about their illness and anticoagulation related quality of life. The anticoagulation database at King's College Hospital will be interrogated and two groups of patients will be identified; those with a time in therapeutic range on warfarin of ≥75 % and those <50 %. These groups of patients will have their illness perceptions, anticoagulation specific quality of life and beliefs about medications compared. Those patients in the time in therapeutic range <50 % group, will be then be invited to switch to a novel oral anticoagulant, as per local guidance. Those patients, who do switch, will then be followed longitudinally and have their adherence, illness perceptions, anticoagulation specific quality of life and beliefs about medications, re-evaluated on the novel agent. The results from these sub-studies, will inform a clinical pathway to support patients on these novel agents, which will be evaluated in an independent group of patients. The results from the switching study will be used to develop a clinical pathway to support patient's prescribed novel oral anticoagulant therapy long-term.

In-vitro anticoagulant activity of fucoidan derivatives from brown seaweed Laminaria japonica

NASA Astrophysics Data System (ADS)

Wang, Jing; Zhang, Quanbin; Zhang, Zhongshan; Hou, Yun; Zhang, Hong

2011-05-01

Fucoidan, a group of sulfated heteropolysaccharides, was extracted from Laminaria japonica, an important economic alga species in China. The anticoagulant activity of fucoidan and its derivatives (including sulfated, phosphorylated, and aminated fucoidan) was examined using in-vitro anticoagulant systems. The correlation between chemical variations within the fucoidan group and anticoagulant activity was determined. The in-vitro anticoagulant properties of fucoidan and its derivatives were determined by measuring activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results indicate anticoagulant activity in all samples using APTT and TT assays; however, only the fucoidan derivatives affected the PT assay. Thus, the fucoidan derivatives were able to inhibit both intrinsic and extrinsic blood coagulants. Fucoidan (FPS) and its derivatives presented better anticoagulant activity than low molecular weight fucoidan (DFPS) and its derivatives, suggesting that molecular weight and proper conformation are contributing factors for anticoagulant activity of polysaccharides. Amino groups have a positive charge and can thus change the charge density of fucoidan. Accordingly, among the tested samples, aminated fucoidan (NF) was the most active reflecting the importance of charge density for anticoagulant activity. Available data obtained using in-vitro models suggest that the sulfate content, sulfate/total-sugar ratio, molecular weight, and the substituted group of fucoidan are important factors for anticoagulant activity but that the influence of sulfate, phosphate and amino groups on anticoagulant activity was different.

Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance.

PubMed

Martin, Karlyn A; Lee, Craig R; Farrell, Timothy M; Moll, Stephan

2017-05-01

Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Anticoagulant and antithrombotic drugs in pregnancy: what are the anesthetic implications for labor and cesarean delivery?

PubMed

Butwick, A J; Carvalho, B

2011-02-01

Neuraxial anesthetic techniques are commonly used during the peripartum period to provide effective pain relief for labor and anesthesia during cesarean delivery. Major neurologic complications are rare after neuraxial anesthesia; however, spinal hematoma is associated with catastrophic neurologic outcomes (including lower-limb paralysis). Anticoagulant and antithrombotic drugs can increase the risk of spinal hematoma after neuraxial anesthesia, and better understanding of the pharmacokinetics and pharmacodynamics of anticoagulants has led to greater appreciation for withholding anticoagulation before and after neuraxial anesthesia. A number of national anesthetic societies have produced guidelines for performing neuraxial anesthesia in patients receiving anticoagulation. However, there is limited information about anesthetic implications of anticoagulation during the peripartum period. This article will review the risks of spinal hematoma after neuraxial anesthesia in pregnant patients; current guidelines for neuraxial anesthesia for anticoagulated patients; and relevant pharmacological data of specific anticoagulant and antithrombotic drugs in pregnancy.

Health care expenditures and therapeutic outcomes of a pharmacist-managed anticoagulation service versus usual medical care.

PubMed

Hall, Deanne; Buchanan, Julianne; Helms, Bethany; Eberts, Matthew; Mark, Scott; Manolis, Chronis; Peele, Pamela; Docimo, Anne

2011-07-01

To evaluate the differences in health care expenditures and therapeutic outcomes of patients receiving warfarin therapy management by a pharmacist-managed anticoagulation service compared with those receiving warfarin management by usual medical care. Retrospective, matched-cohort study. University of Pittsburgh Medical Center (UPMC) and UPMC Health Plan. Three hundred fifty adults who received warfarin therapy; 175 were managed by the pharmacist-managed anticoagulation service for at least 2 months between October 1, 2007, and September 30, 2008, (case patients) and 175 received usual care (matched comparison group). Medical claims data compared were direct anticoagulation cost and overall medical care costs, anticoagulation-related adverse events, hospitalizations and emergency department visits, frequency of international normalized ratio (INR) testing, and quantity of warfarin refills. Operational costs of the anticoagulation service were also calculated. The INR values and time within therapeutic range were assessed through anticoagulation service reports and laboratory results. The direct anticoagulation care cost was $35,465 versus $111,586 and the overall medical care cost was $754,191 versus $1,480,661 for the anticoagulation service group versus the usual care group. Accounting for operational and drug expenditure costs, the cost savings was $647,024 for the anticoagulation service group. The anticoagulation service group had significantly fewer anticoagulation-related adverse events (14 vs 41, p<0.0001), hospital admissions (3 vs 14, p<0.00001), and emergency department visits (58 vs 134, p<0.00001). The percentage of INR values in range and the percentage of time the INR values were in range were significantly higher in the anticoagulation service group (67.2% vs 54.6%, p<0.0001, and 73.7% vs 61.3%, p<0.0001, respectively). Compared with the usual care group, the anticoagulation service group had significantly more INR tests performed but demonstrated no significant difference in the quantity of drug refills. After accounting for operational costs, pharmacist-managed anticoagulation leads to reduced health care expenditure while improving therapeutic outcomes compared with usual medical care.

Prescription frequency and predictors for the use of novel direct oral anticoagulants for secondary stroke prevention in the first year after their marketing in Europe--a multicentric evaluation.

PubMed

Luger, Sebastian; Hohmann, Carina; Kraft, Peter; Halmer, Ramona; Gunreben, Ignaz; Neumann-Haefelin, Tobias; Kleinschnitz, Christoph; Walter, Silke; Haripyan, Veronika; Steinmetz, Helmuth; Foerch, Christian; Pfeilschifter, Waltraud

2014-07-01

Direct oral anticoagulants (DOAC) are alternatives to the use of vitamin K antagonists (VKA) as oral anticoagulant therapies to prevent stroke in patients with atrial fibrillation. We assembled a representative secondary prevention cohort from four tertiary care stroke centers to identify factors that independently influence therapeutic decision making 1) not to anticoagulate with either VKA or DOAC and 2) to use DOAC if the patient appears suitable for oral anticoagulant therapy. We identified all patients discharged with the diagnoses 'ischemic stroke' (ICD-10 code I63) or 'transient ischemic attack' (G45) in combination with 'atrial fibrillation' (I48) during 1 year. We performed binary logistic regression analyses to identify factors independently influencing the aforementioned decisions. Our cohort comprised 758 patients. At discharge from the stroke service, 374 patients (49·3%) received oral anticoagulant therapy. Older age, severe stroke, poor recovery in the acute phase, and higher serum creatinine were independent factors to withhold oral anticoagulant therapy, whereas prior oral anticoagulant therapy favored the decision to anticoagulate. Among patients who were anticoagulated, prescription was balanced for VKA (50·3%) and DOAC (49·7%). Renal function and prior oral anticoagulant therapies were the most important factors in this decision. Shortly after their marketing, DOAC are used as frequently as VKA for secondary stroke prevention in patients with atrial fibrillation. The decision between VKA and DOAC is mainly determined by the patient's renal function and the absence or presence of prior oral anticoagulant therapy. © 2014 World Stroke Organization.

Simulation Models Evaluation of Pest Resistance Development to Refuge in the Bag Concepts Related to Pioneer Submission

EPA Science Inventory

The USEPA, under its administration of the Federal Insecticide Fungicide and Rodenticide Act (FIFRA), requires the registration of all pesticides and pesticidal materials. The GM crops containing pesticidal traits are subject to FIFRA registration requirements. Concerns relating ...

An EPA Modeling Dashboard for Ecological Assessment of Pesticides

EPA Science Inventory

The EPA registers pesticides for use in the US and approves imported pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Before a pesticide can be registered, the EPA must assess whether the pesticide can be used without eing harmful to humans or pos...

Cheminformatics Applications and Physicochemical Property Calculators: A Powerful Combination for the Encoding of Process Science

EPA Science Inventory

The registration of new chemicals under the Toxic Substances Control Act (TSCA) and new pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) requires knowledge of the process science underlying the transport and transformation of organic chemicals in n...

Chapter 5. Pesticide Regulations: Exposure-dose modeling from FIFRA to FQPA

EPA Science Inventory

The federal laws and regulations governing the registration and use of pesticides in the United States under the Federal Insecticide, Fungicide, and Rodenticide Act are published in the Federal Register, while state laws such as California are published in the California Food an...

40 CFR 164.51 - Other discovery.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Other discovery. 164.51 Section 164.51... GOVERNING HEARINGS, UNDER THE FEDERAL INSECTICIDE, FUNGICIDE, AND RODENTICIDE ACT, ARISING FROM REFUSALS TO... OTHER HEARINGS CALLED PURSUANT TO SECTION 6 OF THE ACT General Rules of Practice Concerning Proceedings...

The effects of glyphosate and aminopyralid on a multi-species plant field trial

EPA Science Inventory

In the United States, the US EPA has the responsibility for the registration of pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act. Prior to registration applicants must demonstrate their product will not adversely affect human health or the environment. Th...

77 FR 48899 - Flutriafol; Pesticide Tolerances for Emergency Exemptions

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2012-08-15

... cotton, undelinted seed; cotton, meal; cotton, refined oil; and cotton gin byproducts. This action is in..., and Rodenticide Act (FIFRA) authorizing use of the pesticide on cotton. This regulation establishes a maximum permissible level for residues of flutriafol in or on cotton commodities. The time-limited...

78 FR 36774 - Agency Information Collection Activities; Proposed Collection; Comment Request; Pesticide...

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... Activities; Proposed Collection; Comment Request; Pesticide Registration Fees Program AGENCY: Environmental... collection activity or ICR does this action apply to? Title: Pesticide Registration Fees Program. ICR number... under Sections 3 and 24(c) of the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). In...

40 CFR 164.101 - Appeals from or review of initial decisions.

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2010-07-01

... decisions. 164.101 Section 164.101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... appeal such exceptions to the Environmental Appeals Board for decision by filing them in writing with the...

40 CFR 164.101 - Appeals from or review of initial decisions.

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2011-07-01

... decisions. 164.101 Section 164.101 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... appeal such exceptions to the Environmental Appeals Board for decision by filing them in writing with the...

40 CFR 164.80 - Order of proceeding and burden of proof.

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2011-07-01

... proof. 164.80 Section 164.80 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF CLASSIFICATIONS... and burden of proof. (a) At the hearing, the proponent of cancellation or change in classification has...

November 6, 2017, Virtual Meeting on the Charge Questions for the Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA SAP) Meeting on Endocrine Disruption

EPA Pesticide Factsheets

This virtual FIFRA SAP meeting will be discus questions on Continuing Development of Alternative High-Throughput Screens to Determine Endocrine Disruption, focusing on Androgen Receptor, Steroidogenesis, and Thyroid Pathways

Delivery of optimized inpatient anticoagulation therapy: consensus statement from the anticoagulation forum.

PubMed

Nutescu, Edith A; Wittkowsky, Ann K; Burnett, Allison; Merli, Geno J; Ansell, Jack E; Garcia, David A

2013-05-01

To provide recommendations for optimized anticoagulant therapy in the inpatient setting and outline broad elements that need to be in place for effective management of anticoagulant therapy in hospitalized patients; the guidelines are designed to promote optimization of patient clinical outcomes while minimizing the risks for potential anticoagulation-related errors and adverse events. The medical literature was reviewed using MEDLINE (1946-January 2013), EMBASE (1980-January 2013), and PubMed (1947-January 2013) for topics and key words including, but not limited to, standards of practice, national guidelines, patient safety initiatives, and regulatory requirements pertaining to anticoagulant use in the inpatient setting. Non-English-language publications were excluded. Specific MeSH terms used include algorithms, anticoagulants/administration and dosage/adverse effects/therapeutic use, clinical protocols/standards, decision support systems, drug monitoring/methods, humans, inpatients, efficiency/ organizational, outcome and process assessment (health care), patient care team/organization and administration, program development/standards, quality improvement/organization and administration, thrombosis/ drug therapy, thrombosis/prevention and control, risk assessment/standards, patient safety/standards, and risk management/methods. Because of this document's scope, the medical literature was searched using a variety of strategies. When possible, recommendations are supported by available evidence; however, because this paper deals with processes and systems of care, high-quality evidence (eg, controlled trials) is unavailable. In these cases, recommendations represent the consensus opinion of all authors and are endorsed by the Board of Directors of the Anticoagulation Forum, an organization dedicated to optimizing anticoagulation care. The board is composed of physicians, pharmacists, and nurses with demonstrated expertise and experience in the management of patients receiving anticoagulation therapy. Recommendations for delivering optimized inpatient anticoagulation therapy were developed collaboratively by the authors and are summarized in 8 key areas: (1) process, (2) accountability, (3) integration, (4) standards of practice, (5) provider education and competency, (6) patient education, (7) care transitions, and (8) outcomes. Recommendations are intended to inform the development of coordinated care systems containing elements with demonstrated benefit in improvement of anticoagulation therapy outcomes. Recommendations for delivering optimized inpatient anticoagulation therapy are intended to apply to all clinicians involved in the care of hospitalized patients receiving anticoagulation therapy. Anticoagulants are high-risk medications associated with a significant rate of medication errors among hospitalized patients. Several national organizations have introduced initiatives to reduce the likelihood of patient harm associated with the use of anticoagulants. Health care organizations are under increasing pressure to develop systems to ensure the safe and effective use of anticoagulants in the inpatient setting. This document provides consensus guidelines for anticoagulant therapy in the inpatient setting and serves as a companion document to prior guidelines relevant for outpatients.

Vena cava filter retrieval in therapeutically anticoagulated patients.

PubMed

Schmelzer, Thomas M; Christmas, A Britton; Taylor, Dennis A; Heniford, B Todd; Sing, Ronald F

2008-12-01

Vena cava filters (VCFs) are indicated in patients with active venous thromboembolism and are a contraindication to therapeutic anticoagulation. When patients can be anticoagulated, VCFs can be removed; however, patients often have anticoagulation discontinued during the retrieval procedure, leaving them at risk for pulmonary embolism (PE). The authors evaluated their experience with retrieving VCFs in therapeutically anticoagulated patients. Data from a prospectively collected database of patients with VCFs placed between January 2005 and September 2007 were reviewed. The retrievals in therapeutically anticoagulated patients (international normalized ratio, 2.0-3.4) were performed using a strict protocol, including preretrieval and postretrieval cavograms. All retrievals were performed in the operating room, and patients were discharged home the same day and examined within 7 to 14 days. Descriptive statistics including means and counts were calculated. One hundred thirteen VCF removals occurred during the study period; 62 were attempted on anticoagulated patients (42 male and 20 female patients; mean age, 36.5 years). Thirty-five patients (56%) had VCFs placed for prophylaxis, 22 (35%) had deep venous thromboses or PEs but had contraindications to anticoagulation, and 5 (8%) were on anticoagulation, which was discontinued perioperatively for major surgical operations. The mean time the filters were in place was 153.7 days (range, 22-684 days). No extravasation was seen on postretrieval cavography. Eight of 62 removal attempts in anticoagulated patients were unsuccessful. One patient had a postoperative pneumothorax that was successfully managed without intervention. There were no operative bleeding complications, and no hematomas or contusions were seen at follow-up. The retrieval of VCFs in therapeutically anticoagulated patients can be performed without complication. Given the perioperative risk for PE, anticoagulation should not be discontinued for VCF retrieval.

Underuse of Anticoagulation in Older Patients with Atrial Fibrillation and CHADS2 Score ≥ 2: Are We Doing Better Since the Marketing of Direct Oral Anticoagulants?

PubMed

Henrard, Séverine; Vandenabeele, Caroline; Marien, Sophie; Boland, Benoit; Dalleur, Olivia

2017-11-01

Our objectives were to (1) describe the evolution of the underuse of anticoagulants in older people with atrial fibrillation (AF) and a CHADS 2 score ≥ 2 since direct oral anticoagulants (DOACs) were introduced to the market and (2) describe factors associated with this underuse. We conducted a retrospective cross-sectional study including geriatric patients admitted during the pre-DOAC (2008-2011) and post-DOAC (2013-2015) periods in an academic hospital in Belgium. Five inclusion criteria were met: age ≥ 75 years, diagnosis of AF, indication for anticoagulation (CHADS 2 score ≥ 2), risk of functional decline (Identification of Seniors At Risk [ISAR] score ≥ 2), and comprehensive geriatric assessment. The use of anticoagulants and antiplatelets at home before admission was recorded. Risks of stroke and bleeding were calculated using CHADS 2 and HEMORR 2 HAGES scores, respectively. Three different logistic regression models were performed to describe the evolution of and factors associated with the underuse of anticoagulants after DOAC marketing. Anticoagulant underuse, present in 209 of 614 (34%) geriatric patients with AF, was lower in patients with a history of stroke (28.5%) or congestive heart failure (26.9%) but higher in those receiving antiplatelets (56.2%) and in older individuals. Anticoagulant underuse decreased significantly from the pre-DOAC (37.3%) to the post-DOAC (29.7%) era, as shown by two analyses using propensity scores. In older patients with AF, anticoagulant underuse was mainly associated with antiplatelet use. Anticoagulant underuse and antiplatelet use have both decreased since DOAC marketing. Underuse of anticoagulants was still a concern for three in ten geriatric patients with AF at high risk of stroke (CHADS 2 score ≥ 2).

76 FR 24047 - Palmyra Atoll National Wildlife Refuge, U.S. Pacific Island Territory; Nonnative Rat Eradication...

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...). The comments we received covered topics such as threats to nontarget species, our proposed selection... eradication, threats to nontarget species, our proposed selection of the rodenticide brodifacoum over... directional manner to all potential rat territories within a short operational period. Special measures to...

75 FR 51036 - Pesticide Emergency Exemptions; Agency Decisions and State and Federal Agency Crisis Declarations

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2010-08-18

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2010-0597; FRL-8840-4] Pesticide Emergency Exemptions..., Fungicide, and Rodenticide Act (FIFRA) for use of pesticides as listed in this notice. The exemptions were...), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington...

77 FR 66834 - Pesticide Emergency Exemptions; Agency Decisions and State and Federal Agency Crisis Declarations

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... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2012-0019; FRL-9362-1] Pesticide Emergency Exemptions..., Fungicide, and Rodenticide Act (FIFRA) for use of pesticides as listed in this notice. The exemptions were...), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC...

77 FR 59561 - Sulfoxaflor; Pesticide Tolerances for Emergency Exemptions

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2012-09-28

... metabolites and degradates in or on cotton, undelinted seed; cotton, gin byproducts; and cotton, hulls. This... Insecticide, Fungicide, and Rodenticide Act (FIFRA) authorizing use of the pesticide on cotton. This... or on cotton, undelinted seed at 0.2 parts per million (ppm); cotton, gin byproducts at 6.0 ppm; and...

77 FR 16829 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

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2012-03-22

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OECA-2011-0824; FRL-9513-7] Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment Request; Pesticide Registration Application... regulations is consolidated in 40 CFR part 9. Abstract: The Federal Insecticide, Fungicide, and Rodenticide...

77 FR 29339 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

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2012-05-17

... Activities; Submission to OMB for Review and Approval; Comment Request; Foreign Purchaser Acknowledgement... nature of the information collection activity and its expected burden and costs. DATES: Additional...(a)(2) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) requires an exporter of any...

77 FR 23713 - Pesticides; Final Guidance on Material Safety Data Sheets as Pesticide Labeling; Request for...

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2012-04-20

... pesticides registered under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and the Material... the information collection activities and related burden estimates associated with the guidance provided in PR Notice 2012-1. DATES: Comments on the Agency's information collection activities and related...

Socio-Economic Condition and the Risk of Zika: Risk Mapping in Brownsville, TX

EPA Science Inventory

EPA has a Congressional mandate to support and promote the use of IPM. Both Federal Insecticide Fungicide and Rodenticide Act (FIFRA) and the Food Quality Protection Act (FQPA) contain language directing EPA to cooperate with various partners to further the use of IPM. Congress m...

40 CFR 164.40 - Qualifications and duties of Administrative Law Judge.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Administrative Law Judge. 164.40 Section 164.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY..., AND RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES OF... recording of the proceedings on the record over the objection of any party. (e) Absence or change of the...

40 CFR 164.100 - Appeals from or review of interlocutory orders or rulings.

Code of Federal Regulations, 2011 CFR

2011-07-01

... interlocutory orders or rulings. 164.100 Section 164.100 Protection of Environment ENVIRONMENTAL PROTECTION..., FUNGICIDE, AND RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES... matter of right shall lie to the Environmental Appeals Board only from an initial or accelerated decision...

40 CFR 164.100 - Appeals from or review of interlocutory orders or rulings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... interlocutory orders or rulings. 164.100 Section 164.100 Protection of Environment ENVIRONMENTAL PROTECTION..., FUNGICIDE, AND RODENTICIDE ACT, ARISING FROM REFUSALS TO REGISTER, CANCELLATIONS OF REGISTRATIONS, CHANGES... matter of right shall lie to the Environmental Appeals Board only from an initial or accelerated decision...

40 CFR 180.284 - Zinc phosphide; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Zinc phosphide; tolerances for... § 180.284 Zinc phosphide; tolerances for residues. (a) General. Tolerances are established for residues of the phosphine resulting from the use of the rodenticide zinc phosphide in or on the raw...

78 FR 24195 - Product Cancellation Order for Certain Pesticide Registrations

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2013-04-24

... Insecticide, Fungicide, and Rodenticide Act (FIFRA). This cancellation order follows a December 19, 2012... effective December 31, 2016. FOR FURTHER INFORMATION CONTACT: Molly Clayton, Pesticide Re-Evaluation... registrants of the products in Tables 1. and 2. of this unit, in sequence by EPA company number. This number...

78 FR 32248 - Notice of Receipt of a Request to Voluntarily Cancel Certain Pesticide Registrations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

...). ACTION: Notice. SUMMARY: In accordance with the Federal Insecticide, Fungicide, and Rodenticide Act... for the allethrins end-use products will be effective December 31, 2016, as described in Unit II. If... 2020. The technical registrants (Sumitomo Chemical Company Limited and Valent BioSciences Corporation...

76 FR 77824 - Dicofol; Cancellation Order for Certain Pesticide Registrations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-14

... Insecticide, Fungicide, and Rodenticide Act (FIFRA), as amended. This cancellation order follows a June 22..., in sequence by EPA company number. Table 3--Registrants of Cancelled Products EPA company No. Company... products identified shall be allowed until October 31, 2016, and thereafter, only for the purposes of...

Decision Support and Web-based Implementation of Algorithms for the Ecological Assessment of Pesticides

EPA Science Inventory

The EPA registers pesticides for use in the US and approves imported pesticides under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Before a pesticide can be registered, the EPA must assess whether the pesticide can be used without being harmful to humans or po...

Oral and parenteral anticoagulants: new kids on the block.

PubMed

Aditya, S

2012-01-01

Well-documented drawbacks of traditional anticoagulants have lead to the quest for an ideal anticoagulant resulting in a surge of novel anticoagulant molecules. These newer agents directly target specific steps in coagulation cascade and include newer low molecular weight heparins (adomiparin), ultra low molecular weight heparins (semuloparin, RO-14), inhibitors of activated factor II (dabigatran, AZD0837), X (rivaroxaban, apixaban, edoxaban, betrixaban), IX (REG1,2), XI (antisense oligonucleotides, BMS 262084, clavatadine A), VII/tissue factor (tifacogin, PCI 274836, and BMS 593214), V (recomodulin, solulin), VIII (TB402), dual thrombin/factor X inhibitors (EP21709, tanogitran), and newer vitamin K antagonists (tecarfarin). Direct thrombin inhibitors and Factor X inhibitors are the most clinically advanced. This article discusses the recent advances in the development of novel targets of anticoagulants. Medline, EMBASE, cochrane database, medscape, SCOPUS, and clinicaltrials.gov were searched using terms "anticoagulants", "blood coagulation inhibitors", "anticoagulants and venous thromboembolism", "anticoagulants and atrial fibrillation", and "'antithrombins." Journal articles published from 2007 to 2012 discussing pharmacology and/or clinical trials were screened.

[Oral anticogulation for non-valvular atrial fibrilation in the elderly].

PubMed

Veiga Fernández, Fernando; Malfeito Jiménez, María del Rocío; Barros Cerviño, Sonia María; Magariños Losada, María del Mar

2015-01-01

Anticoagulation in elderly people with non-valvular atrial afibrillation (AF) is a challenge, due to the thromboembolic, as well as the haemorrhagic risks. The correct use of anticoagulants in these patients has shown a higher net clinical benefit when comparing it with a younger population. Non-vitamin K antagonist oral anticoagulants (NOACs) have been compared to oral vitamin K antagonists in several studies that included a sufficient number of elderly people. Favourable results for non-vitamin K antagonist oral anticoagulants were obtained in these studies, making them the preferred treatment for this group of patients. Basing the estimations on indirect comparisons, the ideal anticoagulant and the specific dose for each particular case has been determined. Finally, a new algorithm has been developed that relates these parameters. Geriatric assessment is the key to the indication for an anticoagulation, the type of anticoagulant needed, and also the best way to optimise all the factors for a safe anticoagulation. The arrival of non-vitamin K antagonist oral anticoagulants will enhance the efficient thromboembolic prophylaxis rate in elderly people with AF. This new treatment will remove different controversial prophylaxis, such as antiaggregants. Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: The SAMURAI‐NVAF Study

PubMed Central

Arihiro, Shoji; Todo, Kenichi; Yamagami, Hiroshi; Kimura, Kazumi; Furui, Eisuke; Terasaki, Tadashi; Shiokawa, Yoshiaki; Kamiyama, Kenji; Takizawa, Shunya; Okuda, Satoshi; Okada, Yasushi; Kameda, Tomoaki; Nagakane, Yoshinari; Hasegawa, Yasuhiro; Mochizuki, Hiroshi; Ito, Yasuhiro; Nakashima, Takahiro; Takamatsu, Kazuhiro; Nishiyama, Kazutoshi; Kario, Kazuomi; Sato, Shoichiro; Koga, Masatoshi; Nagatsuka, K; Minematsu, K; Nakagawara, J; Akiyama, H; Shibazaki, K; Maeda, K; Shibuya, S; Yoshimura, S; Endo, K; Miyagi, T; Osaki, M; Kobayashi, J; Okata, T; Tanaka, E; Sakamoto, Y; Takizawa, H; Takasugi, J; Tokunaga, K; Homma, K; Kinoshita, N; Matsuki, T; Higashida, K; Shiozawa, M; Kanai, H; Uehara, S

2015-01-01

Background Large clinical trials are lack of data on non‐vitamin K antagonist oral anticoagulants for acute stroke patients. Aim To evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk‐factor Assessment and Improvement‐NVAF registry (ClinicalTrials.gov NCT01581502). Method The study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23‐day stay) was assessed. Results Warfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10‐month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS 2, CHA 2 DS 2‐VASc, and HAS‐BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four‐days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20‐day or shorter hospitalization (OR 2·46, 95% CI 1·87–3·24). Conclusions Warfarin use at acute hospital discharge was still common in the initial years after approval of nonvitamin K antagonist oral anticoagulants, although nonvitamin K antagonist oral anticoagulant users increased gradually. The index stroke was milder and ischemia‐risk indices were lower in nonvitamin K antagonist oral anticoagulant users than in warfarin users. Early initiation of nonvitamin K antagonist oral anticoagulants seemed safe. PMID:25581108

Early Transcatheter Aortic Valve Function With and Without Therapeutic Anticoagulation.

PubMed

Hiremath, Pranoti G; Kearney, Kathleen; Smith, Bryn; Don, Creighton; Dvir, Danny; Aldea, Gabriel; Reisman, Mark; McCabe, James M

2017-11-01

Prosthetic leaflet thrombosis is a growing concern in transcatheter aortic valve replacement (TAVR). Given the uncertainty of best practices for antiplatelet and anticoagulation therapies in the post-TAVR period, additional evidence regarding the impact of anticoagulation on prosthetic valve function after TAVR is needed. Patients undergoing native-valve TAVR at a single academic institution between 2012 and 2015 were analyzed based on any anticoagulant use at hospital discharge post TAVR. Changes in prosthetic valve peak velocity and mean gradient were assessed based on transthoracic echocardiograms performed immediately following valve implant and at 4-week follow-up. Multivariate regression analyses were performed to explore the impact of anticoagulation status on early TAVR valve performance. For 403 patients, there were no available data to analyze. Of those, 29.6% were discharged on anticoagulation. Following TAVR, the average mean prosthetic valve gradient was 11.8 ± 5.6 mm Hg and peak velocity was 2.33 ± 0.52 m/s. There were no significant differences between anticoagulated and non-anticoagulated groups in the mean or peak gradients or velocity immediately following implant or at 4 weeks, which remained true following multivariate adjustment (P=.80 for delta mean gradient; P=.91 for delta peak velocity). Our data suggest that the absence of anticoagulation is not associated with short-term degradation in TAVR performance and do not support the routine use of anticoagulation following native-valve TAVR.

Optimal duration of anticoagulation in patients with venous thromboembolism.

PubMed

Prandoni, Paolo; Piovella, Chiara; Spiezia, Luca; Dalla Valle, Fabio; Pesavento, Raffaele

2011-07-01

The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE.

Recent progress and market analysis of anticoagulant drugs

PubMed Central

Fan, Ping; Gao, Yangyang; Zheng, Minglin; Xu, Ting; Schoenhagen, Paul

2018-01-01

This review describes epidemiology of thromboembolic disease in China and abroad, evaluates trends in the development of anticoagulant drugs, and analyzes the market situation based on large amounts of accumulated data. Specifically, we describe advances in clinical application of anticoagulants and analyze the most commonly used anticoagulants in the market systematically.

Anticoagulant and Antiplatelet Therapy in Patients with Atrial Fibrillation and Coronary Artery Disease

PubMed Central

Mischke, Karl; Knackstedt, Christian; Marx, Nikolaus

2012-01-01

Anticoagulation represents the mainstay of therapy for most patients with atrial fibrillation. Patients on oral anticoagulation often require concomitant antiplatelet therapy, mostly because of coronary artery disease. After coronary stent implantation, dual antiplatelet therapy is necessary. However, the combination of oral anticoagulation and antiplatelet therapy increases the bleeding risk. Risk scores such as the CHA2DS2-Vasc score and the HAS-BLED score help to identify both bleeding and stroke risk in individual patients. The guidelines of the European Society of Cardiology provide a rather detailed recommendation for patients on oral anticoagulation after coronary stent implantation. However, robust evidence is lacking for some of the recommendations, and especially for new oral anticoagulants and new antiplatelets few or no data are available. This review addresses some of the critical points of the guidelines and discusses potential advantages of new anticoagulants in patients with atrial fibrillation after stent implantation. PMID:22577538

Efficacy of aprotinin with various anticoagulant agents in cardiopulmonary bypass.

PubMed

Terrell, M R; Walenga, J M; Koza, M J; Pifarré, R

1996-08-01

Aprotinin has recently been approved for clinical use in cardiopulmonary bypass. Although unfractionated heparin has been the only anticoagulant widely used for cardiopulmonary bypass, disadvantages involving heparin have led to ongoing investigations of alternative anticoagulant agents. The objective of this study was to evaluate the efficacy of aprotinin in combination with other anticoagulant agents, specifically low molecular weight heparin and recombinant hirudin, using a dog model of cardiopulmonary bypass. The blood conservation resulting from the use of aprotinin was observed only with unfractionated heparin. Efficacy of anticoagulation as measured by protein deposits in the bypass circuit filter revealed an unexpected reduction in the quantity of deposits when aprotinin was used in combination with low molecular weight heparin. As alternative anticoagulant agents are sought, the potential benefits of aprotinin in the reduction of operative blood loss must be evaluated independently for each anticoagulant agent.

Variability in Antithrombotic Therapy Regimens Peri-TAVR: A Single Academic Center Experience.

PubMed

Rossi, Jeffrey E; Noll, Andrew; Bergmark, Brian; McCabe, James M; Nemer, David; Okada, David R; Vasudevan, Anant; Davidson, Michael; Welt, Frederick; Eisenhauer, Andrew; Shah, Pinak; Giugliano, Robert

2015-12-01

The aim of this study was to describe peri-procedural antithrombotic use in patients undergoing transcatheter aortic valve replacement (TAVR) at a single academic medical center. Retrospective collection of antiplatelet and anticoagulant use during the index hospitalization for all patients undergoing TAVR at our institution from April 2009 through March 2014. Of a total of 255 patients undergoing the procedure, 132 (51%) had an indication for anticoagulation pre-TAVR and 92 (70% of those with an indication) were on treatment. On discharge, 106 patients (44% of total surviving to discharge, 73% of those surviving with an indication for anticoagulation) were treated with oral anticoagulation. Of these patients, 89 (84%) were discharged on aspirin and an oral anticoagulant without clopidogrel. Only 122 (51% of total patients) were discharged on the regimen of aspirin and clopidogrel alone. Peri-procedural antithrombotic regimens vary greatly following TAVR. More than half of patients have an indication for anticoagulation following the procedure. Most patients at our institution who require anticoagulation are discharged on aspirin and an oral anticoagulant, though the optimal regimen requires further investigation.

Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

PubMed

Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

2015-01-01

Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.

The future of anticoagulation clinics.

PubMed

Macik, B Gail

2003-01-01

Anticoagulation therapy is the foundation of treatment for thromboembolic disorders; and coumarin derivatives (warfarin in the United States) are the only orally administered anticoagulant medications currently available. Due to the expense and relative difficulties associated with this route of administration, parenteral drugs are not used routinely for long-term therapy, leaving warfarin as the anticoagulant of choice in the outpatient setting. The management of warfarin is problematic, however, due the nuances of its pharmacodynamic and pharmacokinetic profile and the requirement for frequent monitoring of blood levels. Although management by anticoagulation clinics is considered the gold standard for warfarin therapy, management by an anticoagulation clinic may not be the optimal option from a clinician's view and, in many cases, may not be an option at all. Anticoagulation clinics may impinge on the doctor-patient relationship. Difficulties of communication and reimbursement are not ameliorated by a specialty clinic. Innovations in warfarin management, including patient self-management and computerized dosing programs, are alternatives for improved care that are available with or without input by an anticoagulation service. New oral drugs on the horizon do not require the same intensity of monitoring and do not present the same pharmacodynamic problems associated with warfarin. Warfarin will become obsolete in the foreseeable future. If anticoagulation clinics continue, they must re-define their role as the major part of the workload, warfarin management, disappears. To adapt, clinics must strengthen and enhance their role as coordinators and educators, and less so, managers of anticoagulation therapy.

Optimal duration of anticoagulation in patients with venous thromboembolism

PubMed Central

Prandoni, Paolo; Piovella, Chiara; Spiezia, Luca; Valle, Fabio Dalla; Pesavento, Raffaele

2011-01-01

The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE. PMID:21808129

Risk scores and geriatric profile: can they really help us in anticoagulation decision making among older patients suffering from atrial fibrillation?

PubMed

Maes, Frédéric; Dalleur, Olivia; Henrard, Séverine; Wouters, Dominique; Scavée, Christophe; Spinewine, Anne; Boland, Benoit

2014-01-01

Anticoagulation for the prevention of cardio-embolism is most frequently indicated but largely underused in frail older patients with atrial fibrillation (AF). This study aimed at identifying characteristics associated with anticoagulation underuse. A cross-sectional study of consecutive geriatric patients aged ≥75 years, with AF and clear anticoagulation indication (CHADS₂ [Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack] ≥2) upon hospital admission. All patients benefited from a comprehensive geriatric assessment. Their risks of stroke and bleeding were predicted using CHADS₂ and HEMORR2HAGES (Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age >75 years), Reduced platelet count or function, Rebleed risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, and Stroke) scores, respectively. Anticoagulation underuse was observed in 384 (50%) of 773 geriatric patients with AF (median age 85 years; female 57%, cognitive disorder 33%, nursing home 20%). No geriatric characteristic was found to be associated with anticoagulation underuse. Conversely, anticoagulation underuse was markedly increased in the patients treated with aspirin (odds ratio [OR] [95% confidence interval]: 5.3 [3.8; 7.5]). Other independent predictors of anticoagulation underuse were ethanol abuse (OR: 4.0 [1.4; 13.3]) and age ≥90 years (OR: 2.0 [1.2; 3.4]). Anticoagulation underuse was not inferior in patients with a lower bleeding risk and/or a higher stroke risk and underuse was surprisingly not inferior either in the AF patients who had previously had a stroke. Half of this geriatric population did not receive any anticoagulation despite a clear indication, regardless of their individual bleeding or stroke risks. Aspirin use is the main characteristic associated with anticoagulation underuse.

Risk scores and geriatric profile: can they really help us in anticoagulation decision making among older patients suffering from atrial fibrillation?

PubMed Central

Maes, Frédéric; Dalleur, Olivia; Henrard, Séverine; Wouters, Dominique; Scavée, Christophe; Spinewine, Anne; Boland, Benoit

2014-01-01

Objectives Anticoagulation for the prevention of cardio-embolism is most frequently indicated but largely underused in frail older patients with atrial fibrillation (AF). This study aimed at identifying characteristics associated with anticoagulation underuse. Methods A cross-sectional study of consecutive geriatric patients aged ≥75 years, with AF and clear anticoagulation indication (CHADS2 [Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack] ≥2) upon hospital admission. All patients benefited from a comprehensive geriatric assessment. Their risks of stroke and bleeding were predicted using CHADS2 and HEMORR2HAGES (Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age >75 years), Reduced platelet count or function, Rebleed risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, and Stroke) scores, respectively. Results Anticoagulation underuse was observed in 384 (50%) of 773 geriatric patients with AF (median age 85 years; female 57%, cognitive disorder 33%, nursing home 20%). No geriatric characteristic was found to be associated with anticoagulation underuse. Conversely, anticoagulation underuse was markedly increased in the patients treated with aspirin (odds ratio [OR] [95% confidence interval]: 5.3 [3.8; 7.5]). Other independent predictors of anticoagulation underuse were ethanol abuse (OR: 4.0 [1.4; 13.3]) and age ≥90 years (OR: 2.0 [1.2; 3.4]). Anticoagulation underuse was not inferior in patients with a lower bleeding risk and/or a higher stroke risk and underuse was surprisingly not inferior either in the AF patients who had previously had a stroke. Conclusion Half of this geriatric population did not receive any anticoagulation despite a clear indication, regardless of their individual bleeding or stroke risks. Aspirin use is the main characteristic associated with anticoagulation underuse. PMID:25053883

Optical sensing of anticoagulation status: Towards point-of-care coagulation testing

PubMed Central

Tripathi, Markandey M.; Hajjarian, Zeinab; Van Cott, Elizabeth M.; Nadkarni, Seemantini K.

2017-01-01

Anticoagulant overdose is associated with major bleeding complications. Rapid coagulation sensing may ensure safe and accurate anticoagulant dosing and reduce bleeding risk. Here, we report the novel use of Laser Speckle Rheology (LSR) for measuring anticoagulation and haemodilution status in whole blood. In the LSR approach, blood from 12 patients and 4 swine was placed in disposable cartridges and time-varying intensity fluctuations of laser speckle patterns were measured to quantify the viscoelastic modulus during clotting. Coagulation parameters, mainly clotting time, clot progression rate (α-angle) and maximum clot stiffness (MA) were derived from the clot viscoelasticity trace and compared with standard Thromboelastography (TEG). To demonstrate the capability for anticoagulation sensing in patients, blood samples from 12 patients treated with warfarin anticoagulant were analyzed. LSR clotting time correlated with prothrombin and activated partial thromboplastin time (r = 0.57–0.77, p<0.04) and all LSR parameters demonstrated good correlation with TEG (r = 0.61–0.87, p<0.04). To further evaluate the dose-dependent sensitivity of LSR parameters, swine blood was spiked with varying concentrations of heparin, argatroban and rivaroxaban or serially diluted with saline. We observed that anticoagulant treatments prolonged LSR clotting time in a dose-dependent manner that correlated closely with TEG (r = 0.99, p<0.01). LSR angle was unaltered by anticoagulation whereas TEG angle presented dose-dependent diminution likely linked to the mechanical manipulation of the clot. In both LSR and TEG, MA was largely unaffected by anticoagulation, and LSR presented a higher sensitivity to increased haemodilution in comparison to TEG (p<0.01). Our results establish that LSR rapidly and accurately measures the response of various anticoagulants, opening the opportunity for routine anticoagulation monitoring at the point-of-care or for patient self-testing. PMID:28771571

Thromboprophylaxis for Patients with High-risk Atrial Fibrillation and Flutter Discharged from the Emergency Department.

PubMed

Vinson, David R; Warton, E Margaret; Mark, Dustin G; Ballard, Dustin W; Reed, Mary E; Chettipally, Uli K; Singh, Nimmie; Bouvet, Sean Z; Kea, Bory; Ramos, Patricia C; Glaser, David S; Go, Alan S

2018-03-01

Many patients with atrial fibrillation or atrial flutter (AF/FL) who are high risk for ischemic stroke are not receiving evidence-based thromboprophylaxis. We examined anticoagulant prescribing within 30 days of receiving dysrhythmia care for non-valvular AF/FL in the emergency department (ED). This prospective study included non-anticoagulated adults at high risk for ischemic stroke (ATRIA score ≥7) who received emergency AF/FL care and were discharged home from seven community EDs between May 2011 and August 2012. We characterized oral anticoagulant prescribing patterns and identified predictors of receiving anticoagulants within 30 days of the index ED visit. We also describe documented reasons for withholding anticoagulation. Of 312 eligible patients, 128 (41.0%) were prescribed anticoagulation at ED discharge or within 30 days. Independent predictors of anticoagulation included age (adjusted odds ratio [aOR] 0.89 per year, 95% confidence interval [CI] 0.82-0.96); ED cardiology consultation (aOR 1.89, 95% CI [1.10-3.23]); and failure of sinus restoration by time of ED discharge (aOR 2.65, 95% CI [1.35-5.21]). Reasons for withholding anticoagulation at ED discharge were documented in 139 of 227 cases (61.2%), the most common of which were deferring the shared decision-making process to the patient's outpatient provider, perceived bleeding risk, patient refusal, and restoration of sinus rhythm. Approximately 40% of non-anticoagulated AF/FL patients at high risk for stroke who presented for emergency dysrhythmia care were prescribed anticoagulation within 30 days. Physicians were less likely to anticoagulate older patients and those with ED sinus restoration. Opportunities exist to improve rates of thromboprophylaxis in this high-risk population.

Preemptive Anticoagulation in Patients With a High Pretest Probability of Pulmonary Embolism: Are Guidelines Followed?

PubMed

Willoughby, Laura; Adams, Daniel M; Evans, R Scott; Lloyd, James F; Stevens, Scott M; Woller, Scott C; Bledsoe, Joseph R; Aston, Valerie T; Wilson, Emily L; Elliott, C Gregory

2018-05-01

Guidelines suggest anticoagulation of patients with high pretest probability of pulmonary embolism (PE) while awaiting diagnostic test results (preemptive anticoagulation). Data relevant to the practice of preemptive anticoagulation are not available. We reviewed 3,500 consecutive patients who underwent CT pulmonary angiography (CTPA) at two EDs. We classified the pretest probability for PE using the revised Geneva Score (RGS) as low (RGS 0-3), intermediate (RGS 4-10), or high (RGS 11-18). We classified patients with a high pretest probability of PE as receiving preemptive anticoagulation if therapeutic anticoagulation was given before CTPA completion. Patients with a high bleeding risk and those receiving treatment for DVT before CTPA were excluded from the preemptive anticoagulation analysis. We compared the time elapsed between ED registration and CTPA completion for patients with a low, intermediate, and high pretest probability for PE. We excluded three of 3,500 patients because CTPA preceded ED registration. Of the remaining 3,497 patients, 167 (4.8%) had a high pretest probability for PE. After excluding 29 patients for high bleeding risk and 21 patients who were treated for DVT prior to CTPA, only two of 117 patients (1.7%) with a high pretest probability for PE received preemptive anticoagulation. Furthermore, 37 of the remaining 115 patients (32%) with a high pretest probability for PE had a preexisting indication for anticoagulation but did not receive preemptive anticoagulation. The time from ED registration to CTPA completion did not differ based on the pretest probability of PE. Physicians rarely use preemptive anticoagulation in patients with a high pretest probability for PE. Clinicians do not expedite CTPA examinations for patients with a high pretest probability for PE. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Cost Effectiveness of Implantable Cardiac Monitor-Guided Intermittent Anticoagulation for Atrial Fibrillation: An Analysis of the REACT.COM Pilot Study.

PubMed

Steinhaus, Daniel A; Zimetbaum, Peter J; Passman, Rod S; Leong-Sit, Peter; Reynolds, Matthew R

2016-08-30

Anticoagulation guidelines for patients with atrial fibrillation (AF) disregard AF burden. A strategy of targeted anticoagulation with novel oral anticoagulants (NOACs) based on continuous rhythm assessment with an implantable cardiac monitor (ICM) has recently been explored. We evaluated the potential cost-effectiveness of this strategy versus projected outcomes with continuous anticoagulation. We developed a Markov model using data from the Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring (REACT.COM) pilot study (N = 59) and prior NOAC trials to calculate the costs and quality-adjusted life years (QALYs) associated with ICM-guided intermittent anticoagulation for AF versus standard care during a 3-year time horizon. Health state utilities were estimated from the pilot study population using the SF-12. Costs were based on current Medicare reimbursement. Over 14 ± 4 months of follow-up, 18 of 59 patients had 35 AF episodes. The ICM-guided strategy resulted in a 94% reduction in anticoagulant use relative to continuous treatment. There were no strokes, 3 (5.1%) TIAs, 2 major bleeding events (on aspirin) and 3 minor bleeding events with the ICM-guided strategy. The projected total 3-year costs were $12,535 for the ICM-guided strategy versus $13,340 for continuous anticoagulation. Projected QALYs were 2.45 for both groups. Based on a pilot study, a strategy of ICM-guided anticoagulation with NOACs may be cost-saving relative to expected outcomes with continuous anticoagulation, with similar quality-adjusted survival. This strategy could be attractive from a health economic perspective if shown to be safe and effective in a rigorous clinical trial. © 2016 Wiley Periodicals, Inc.

Cost Effectiveness of Implantable Cardiac Monitor-Guided Intermittent Anticoagulation for Atrial Fibrillation: An Analysis of the REACT.COM Pilot Study

PubMed Central

Steinhaus, Daniel A; Zimetbaum, Peter J; Passman, Rod S; Leong-Sit, Peter; Reynolds, Matthew R.

2016-01-01

Introduction Anticoagulation guidelines for patients with atrial fibrillation (AF) disregard AF burden. A strategy of targeted anticoagulation with novel oral anticoagulants (NOACs) based on continuous rhythm assessment with an implantable cardiac monitor (ICM) has recently been explored. We evaluated the potential cost-effectiveness of this strategy versus projected outcomes with continuous anticoagulation. Methods and Results We developed a Markov model using data from the Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring (REACT.COM) pilot study (N=59) and prior NOAC trials to calculate the costs and quality-adjusted life years (QALYs) associated with ICM-guided intermittent anticoagulation for AF vs. standard care over a 3-year time horizon. Health state utilities were estimated from the pilot study population using the SF-12. Costs were based on current Medicare reimbursement. Over 14±4 months of follow-up 18 of 59 patients had 35 AF episodes. The ICM-guided strategy resulted in a 94% reduction in anticoagulant use relative to continuous treatment. There were no strokes, 3 (5.1%) TIAs, 2 major bleeding events (on aspirin) and 3 minor bleeding events with the ICM-guided strategy. The projected total 3-year costs were $12,535 for the ICM-guided strategy vs. $13,340 for continuous anticoagulation. Projected QALYs were 2.45 for both groups. Conclusion Based on a pilot study, a strategy of ICM-guided anticoagulation with NOACs may be cost-saving relative to expected outcomes with continuous anticoagulation, with similar quality-adjusted survival. This strategy could be attractive from a health economic perspective if shown to be safe and effective in a rigorous clinical trial. PMID:27571718

Anticoagulation Use and Clinical Outcomes Following Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation

PubMed Central

Hernandez, Inmaculada; Zhang, Yuting; Brooks, Maria M.; Chin, Paul K.L.; Saba, Samir

2016-01-01

Background and Purpose Little is known about the clinical outcomes associated with post-hemorrhage anticoagulation resumption for atrial fibrillation. This study had two objectives: first, to evaluate anticoagulation use after a first major bleed on warfarin or dabigatran; and second, to compare effectiveness and safety outcomes between patients discontinuing anticoagulation after a major bleed and patients restarting warfarin or dabigatran. Methods Using 2010-2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding event while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their post-hemorrhage use of anticoagulation. We followed them until an ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors impacting anticoagulation resumption, and Cox Proportional Hazard models to compare the combined risk of ischemic stroke and all-cause mortality, and the risk of recurrent bleeding between treatment groups. Results Resumption of anticoagulation with warfarin (hazard ratio (HR) 0.76; 95%CI, 0.59-0.97) or dabigatran (HR0.66; 95%CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients prescribed warfarin after the event than for those prescribed dabigatran (HR2.31; 95%CI, 1.19-4.76) or whose anticoagulation ceased (HR1.56; 95%CI, 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation (HR0.66; 95% CI, 0.32-1.33). Conclusions Dabigatran was associated with a superior benefit/risk ratio than warfarin and anticoagulation discontinuation in the treatment of atrial fibrillation patients who have survived a major bleed. PMID:27909200

Optimizing the use of oral anticoagulant therapy for atrial fibrilation in primary care: a pharmacist-led intervention.

PubMed

Virdee, Mandeep S; Stewart, Derek

2017-02-01

Background Updated evidence-based guidelines for the management of atrial fibrillation (AF) necessitate patient review, particularly with respect to oral anticoagulants, to ensure maximum health gain around stroke prophylaxis. Objective To quantify the level of anticoagulation utilisation in patients with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female) according to evidence-based guidelines and to assess the impact of a pharmacist-led intervention to optimise therapy. Setting Fifteen general medical practices in Liverpool, North-West England with a practice population of 99,129. Method GRASP-AF software was employed to interrogate patient electronic medical records to identify and risk stratify AF patients (using CHA 2 DS 2 -VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female). Recommendations were discussed with a general practitioner (GP) and those patients in whom the need for anticoagulation was agreed were invited for a consultation with either the pharmacist or GP and therapy optimised where appropriate. The GPs were responsible for managing those patients referred for diagnosis confirmation or further specialist opinion. Main outcome measure Proportion of patients eligible/not eligible for anticoagulation; proportions in whom anticoagulants initiated, refused, antiplatelets discontinued. Results Five hundred and twenty-three patients (31% of patients identified with AF and a CHA 2 DS 2 -VASc ≥1/≥2 (male/female)) were not receiving an anticoagulant (26 subsequently died or left the practice leaving 497). Three hundred and eighty-two (77%) pharmacist recommendations to a GP were agreed without modification. Following outcomes of diagnostic investigations and specialist referrals, 202 (41%) patients were candidates for anticoagulation, 251 (51%) were not eligible for anticoagulation, 103 (21%) were anticoagulated (56 warfarin, 47 DOAC). Conclusion A pharmacist-led intervention re-aligned oral anticoagulant therapy to the latest evidence based guidelines for stroke prophylaxis, whilst simultaneously correcting the over-utilisation of antiplatelet therapy.

POST-NOAC: Portuguese observational study of intracranial hemorrhage on non-vitamin K antagonist oral anticoagulants.

PubMed

Marques-Matos, Cláudia; Alves, José Nuno; Marto, João Pedro; Ribeiro, Joana Afonso; Monteiro, Ana; Araújo, José; Silva, Fernando; Grenho, Fátima; Viana-Baptista, Miguel; Sargento-Freitas, João; Pinho, João; Azevedo, Elsa

2017-08-01

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA 2 DS 2 VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39-1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55-2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants- and vitamin K antagonists-associated intracranial hemorrhage, despite unavailability of non-vitamin K antagonist oral anticoagulants-specific reversal agents.

[Gastrointestinal lesions and characteristics of acute gastrointestinal bleeding in acenocoumarol-treated patients].

PubMed

Nantes, Óscar; Zozaya, José Manuel; Montes, Ramón; Hermida, José

2014-01-01

In the last few years, the number of anticoagulated patients has significantly increased and, as a consequence, so have hemorrhagic complications due to this therapy. We analyzed gastrointestinal (GI) bleeding because it is the most frequent type of major bleeding in these patients, and we hypothesized that they would have lesions responsible for GI bleeding regardless of the intensity of anticoagulation, although excessively anticoagulated patients would have more serious hemorrhages. To study the characteristics of anticoagulated patients with GI bleeding and the relationship between the degree of anticoagulation and a finding of causative lesions and bleeding severity. We prospectively studied 96 patients, all anticoagulated with acenocoumarol and consecutively admitted to hospital between 01/01/2003 and 09/30/2005 because of acute GI bleeding. We excluded patients with severe liver disease, as well as nine patients with incomplete details. The incidence of GI bleeding requiring hospitalization was 19.6 cases/100,000 inhabitants-year. In 90% of patients, we found a causative (85% of upper GI bleeding and 50% of lower GI bleeding) or potentially causative lesion, and 30% of them required endoscopic treatment, without differences depending on the intensity of anticoagulation. No relationship was found between the type of lesions observed and the degree of anticoagulation in these patients. Patients who received more intense anticoagulation therapy had more severe hemorrhages (23% of patients with an INR ≥4 had a life-threatening bleed versus only 4% of patients with INR <4). We found an incidence of 20 severe GI bleeding episodes in anticoagulated patients per 100,000 inhabitants-year, with no difference in localization or in the frequency of causative lesions depending on the intensity of anticoagulation. Patients receiving more intense anticoagulation had more severe GI bleeding episodes. Copyright © 2013 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer - A real world experience.

PubMed

Phelps, Megan K; Wiczer, Tracy E; Erdeljac, H Paige; Van Deusen, Kelsey R; Porter, Kyle; Philips, Gary; Wang, Tzu-Fei

2018-01-01

Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry "lower risk" features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.

40 CFR 35.101 - Environmental programs covered by the subpart.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (section 205(g) of the Clean Water Act). (19) Water quality management planning (section 205(j)(2) of the... Drinking Water Act). (6) Hazardous waste management (section 3011(a) of the Solid Waste Disposal Act). (7... Insecticide, Fungicide, and Rodenticide Act). (10) Nonpoint source management (sections 205(j)(5) and 319(h...

Report: EPA Needs to Comply with the Federal Insecticide, Fungicide, and Rodenticide Act and Improve Its Oversight of Exported Never-Registered Pesticides

EPA Pesticide Factsheets

Report #10-P-0026, November 10, 2009. EPA is not complying with FIFRA Section 17(a) which is, in part, intended to notify the government of an importing country that a potentially hazardous pesticide was imported into that country.

75 FR 54622 - Pesticide Emergency Exemptions; Agency Decisions and State and Federal Agency Crisis Declarations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2009-0019; FRL-8843-8] Pesticide Emergency Exemptions..., Fungicide, and Rodenticide Act (FIFRA) for use of pesticides as listed in this notice. The exemptions were... Division (7505P), Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW...

76 FR 4656 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

... Activities; Submission to OMB for Review and Approval; Comment Request; Plant-Incorporated Protectants; CBI... collection activity. An Agency may not conduct or sponsor, and a person is not required to respond to, a... requirements under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). Registrants sometimes...

21 CFR 225.35 - Use of work areas, equipment, and storage areas for other manufacturing and storage purpose.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING..., rodenticides, and other pesticides. Manufacturing, storage, or handling of nonfeed and feed products in the... pesticides unless such articles are approved drugs, indexed drugs, or approved food additives intended for...

78 FR 3420 - Pesticide Emergency Exemptions; Agency Decisions and State and Federal Agency Crisis Declarations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

... human health, including exposure of residues of the pesticide to infants and children. If the emergency... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2012-0019; FRL-9375-2] Pesticide Emergency Exemptions..., Fungicide, and Rodenticide Act (FIFRA) for use of pesticides as listed in this notice. The exemptions were...

77 FR 8860 - Pesticide Emergency Exemptions; Agency Decisions and State and Federal Agency Crisis Declarations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-15

... harm'' to human health, including exposure of residues of the pesticide to infants and children. If the... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2012-0019; FRL-9337-4] Pesticide Emergency Exemptions..., Fungicide, and Rodenticide Act (FIFRA) for use of pesticides as listed in this notice. The exemptions were...

21 CFR 225.35 - Use of work areas, equipment, and storage areas for other manufacturing and storage purpose.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING..., rodenticides, and other pesticides. Manufacturing, storage, or handling of nonfeed and feed products in the... pesticides unless such articles are approved drugs, indexed drugs, or approved food additives intended for...

21 CFR 225.35 - Use of work areas, equipment, and storage areas for other manufacturing and storage purpose.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING..., rodenticides, and other pesticides. Manufacturing, storage, or handling of nonfeed and feed products in the... pesticides unless such articles are approved drugs, indexed drugs, or approved food additives intended for...

21 CFR 225.35 - Use of work areas, equipment, and storage areas for other manufacturing and storage purpose.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING..., rodenticides, and other pesticides. Manufacturing, storage, or handling of nonfeed and feed products in the... pesticides unless such articles are approved drugs, indexed drugs, or approved food additives intended for...

21 CFR 225.35 - Use of work areas, equipment, and storage areas for other manufacturing and storage purpose.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING..., rodenticides, and other pesticides. Manufacturing, storage, or handling of nonfeed and feed products in the... pesticides unless such articles are approved drugs, indexed drugs, or approved food additives intended for...

Neurotoxicoses of small animals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simpson, S.T.

1976-02-01

Among the great variety of potentially neurotoxic substances are insecticides, rodenticides, herbicides, fungicides, heavy metals, plants, drugs, reptile and insect venoms, industrial chemicals and contaminated foodstuffs. The neurotoxicoses associated with several of these are described. Of the insecticides, organophosphates and chlorinated hydrocarbons are discussed. The heavy metals thallium and lead are discussed along with botulism and polyradiculoneuritis. 22 references.

76 FR 51031 - Registration; Cancellation Order for Rodenticide Products That Have Expired

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-17

...--Registrations and Product Names EPA Registration No. Product name 47629-14 Difenacoum Rat and Mouse Pellets (consumer use only). 47629-16 Difenacoum Rat and Mouse Block (consumer use only). 47629-17 Difenacoum Rat and Mouse Place Packs (consumer use only). 47629-11 Bromethalin Rat & Mouse Block. 47629-13...

Chemical Agents of Opportunity for Terrorism Workshop

DTIC Science & Technology

2014-04-01

a 15 month old child who developed status epilepticus describes the first known case in the US of exposure to a rodenticide brought in from China...and Iodine status for thyroid effects? A – I was involved with the first five volumes and do not recall such a chemical (showing toxicities on both

77 FR 75157 - Notice of Receipt of a Request To Voluntarily Cancel Certain Pesticide Registrations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-19

... Rodenticide Act (FIFRA), as amended, EPA is issuing a notice of receipt of request by registrants to... the cancellation for the allethrins end-use products will be effective December 31, 2016, as described... and Sumitomo Chemical Company Limited to cancel all their allethrins pesticide products registered...

78 FR 25438 - Product Cancellation Order for Certain Pesticide Registrations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-01

... Insecticide, Fungicide, and Rodenticide Act (FIFRA). This cancellation order follows a February 20, 2013... products in Table 1 and Table 2 of this unit, in sequence by EPA company number. This number corresponds to... unit. Table 3--Registrants of Cancelled Products EPA Company number Company name and address 279 FMC...

Climate change and other stressors change modeled population size and hybridization potential for San Joaquin kit fox

EPA Science Inventory

The San Joaquin kit fox was once widely distributed across the southern San Joaquin Valley, but agriculture and development have replaced much of the endangered subspecies’ habitat. We modeled impacts of climate change, land-use change, and rodenticide exposure on kit fox p...

48 CFR 1552.235-77 - Data Security for Federal Insecticide, Fungicide and Rodenticide Act Confidential Business...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Data Security for Federal... 1552.235-77 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 1552.235-77 Data Security for...

48 CFR 1552.235-77 - Data Security for Federal Insecticide, Fungicide and Rodenticide Act Confidential Business...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Data Security for Federal... 1552.235-77 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 1552.235-77 Data Security for...

48 CFR 1552.235-77 - Data Security for Federal Insecticide, Fungicide and Rodenticide Act Confidential Business...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Data Security for Federal... 1552.235-77 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 1552.235-77 Data Security for...

48 CFR 1552.235-77 - Data Security for Federal Insecticide, Fungicide and Rodenticide Act Confidential Business...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Data Security for Federal... 1552.235-77 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 1552.235-77 Data Security for...

48 CFR 1552.235-77 - Data Security for Federal Insecticide, Fungicide and Rodenticide Act Confidential Business...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Data Security for Federal... 1552.235-77 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 1552.235-77 Data Security for...

Abnormal uterine bleeding in women receiving direct oral anticoagulants for the treatment of venous thromboembolism.

PubMed

Godin, Richard; Marcoux, Violaine; Tagalakis, Vicky

2017-08-01

Abnormal uterine bleeding (AUB) is a common complication of anticoagulant therapy in premenopausal women affected with acute venous thromboembolism. AUB impacts quality of life, and can lead to premature cessation of anticoagulation. There is increasing data to suggest that the direct oral anticoagulants when used for the treatment of venous thromboembolism differ in their menstrual bleeding profile. This article aims to review the existing literature regarding the association between AUB and the direct oral anticoagulants and make practical recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.

Venous Thromboembolism Requiring Extended Anticoagulation Among HIV-Infected Patients in a Rural, Resource-Constrained Setting in Western Kenya.

PubMed

Kanyi, John; Karwa, Rakhi; Pastakia, Sonak Dinesh; Manji, Imran; Manyara, Simon; Saina, Collins

2017-05-01

HIV-infected patients are at an increased risk of developing venous thromboembolism (VTE), and minimal data are available to describe the need for extended treatment. To evaluate the frequency of and determine predictive risk factors for extended anticoagulation of VTE in HIV-infected patients in rural, western Kenya. A retrospective chart review was conducted at the Anticoagulation Monitoring Service affiliated with Moi Teaching and Referral Hospital and the Academic Model Providing Access to Healthcare. Data were collected on patients who were HIV-infected and receiving anticoagulation for lower-limb deep vein thrombosis. The need for extended anticoagulation, defined as receiving ≥7 months of warfarin therapy, was established based on patient symptoms or Doppler ultrasound-confirmed diagnosis. Evaluation of the secondary outcomes utilized a univariate analysis to identify risk factors associated with extended anticoagulation. A total of 71 patients were included in the analysis; 27 patients (38%) required extended anticoagulation. The univariate analysis showed a statistically significant association between the need for extended anticoagulation and achieving a therapeutic international normalized ratio within 21 days in both the unadjusted and adjusted analysis. Patients with a history of opportunistic infections required an extended duration of anticoagulation in the adjusted analysis: odds ratio = 3.42; 95% CI = 1.04-11.32; P = 0.04. This study shows that there may be a need for increased duration of anticoagulation in HIV-infected patients, with a need to address the issue of long-term management. Guideline recommendations are needed to address the complexity of treatment issues in this population.

Polyguluronate sulfate, polymannuronate sulfate, and their oligosaccharides have antithrombin III- and heparin cofactor II-independent anticoagulant activity

NASA Astrophysics Data System (ADS)

Zeng, Xuan; Lan, Ying; Zeng, Pengjiao; Guo, Zhihua; Hao, Cui; Zhang, Lijuan

2017-04-01

Cardiovascular disease is the leading causes of death. However, the complications can be treated with heparin and heparinoids, such as heparin pentasaccharide Fondaparinux, dermatan sulfate, and PSS made from alginate extracted from brown seaweeds by chemical sulfation. Alginate is composed of a linear backbone of polymannuronate (PM), polyguluronate (PG), and alternate residues of mannuronic acid and guluronic acid. It is unknown if heparin and sulfated PG (PGS)/PM (PMS) have the same or different anticoagulant molecular targets. In the current study, the anticoagulant activities of PGS, PMS, and their oligosaccharides were directly compared to that of heparin, Fondaparinux, and dermatan sulfate by the activated partial thrombinplastin time (aPTT) assay using normal, antithrombin III (ATIII)-deficient, heparin co-factor II (HCII)-deficient, and ATIII- and HCII-double deficient human plasmas. Our results showed that PGS, PMS, and their oligosaccharides had better anticoagulant activity than that of Fondaparinux in all four human plasmas tested. As expected, heparin was the best anticoagulant in normal plasma. Moreover, PGS, PGS6, PGS12, PGS25, PMS6, PMS12, and PMS25 were better anticoagulants than dermatan sulfate in HCII-deficient plasma. Most strikingly, PGS, PGS12, PGS25, PMS6, PMS12, and PMS25 were better anticoagulants than that of heparin in ATIII- and HCII-double deficient human plasma. The results revealed for the first time that sulfated alginate had ATIII- and HCII-independent anticoagulant activities. Therefore, developing PGS and PMS-based anticoagulants might require to discover their major molecular targets and to develop target-specific anticoagulant assays.

Considerations for long-term anticoagulant therapy in patients with venous thromboembolism in the novel oral anticoagulant era.

PubMed

Toth, Peter P

2016-01-01

Patients who have had a venous thromboembolic event are generally advised to receive anticoagulant treatment for 3 months or longer to prevent a recurrent episode. Current guidelines recommend initial heparin and an oral vitamin K antagonist (VKA) for long-term anticoagulation. However, because of the well-described disadvantages of VKAs, including extensive food and drug interactions and the need for regular anticoagulation monitoring, novel oral anticoagulants (NOACs) have become an attractive option in recent years. These agents are given at fixed doses and do not require routine coagulation-time monitoring. The NOACs are discussed in this review with regard to the needs of patients on long-term anticoagulation. Current guidelines from Europe and North America that refer to the treatment of deep vein thrombosis and/or pulmonary embolism are included, as well as published randomized Phase III clinical trials of NOACs. PubMed searches were used for sourcing case studies of long-term anticoagulant treatment, and results were filtered for human application and screened for relevance. NOAC-based therapy showed a similar efficacy and safety profile to heparins/VKAs but without the need for regular anticoagulation monitoring or dietary adjustments, and can be taken as a fixed-dose regimen once or twice daily. This represents a significant step forward in facilitating the management of long-term anticoagulation therapy. Furthermore, in the EINSTEIN studies, improved patient satisfaction was documented with the NOAC rivaroxaban, which may result in better adherence to therapy and an overall reduction in the incidence of recurrent venous thromboembolism.

Heparin bridge therapy and post-polypectomy bleeding.

PubMed

Kubo, Toshiyuki; Yamashita, Kentaro; Onodera, Kei; Iida, Tomoya; Arimura, Yoshiaki; Nojima, Masanori; Nakase, Hiroshi

2016-12-07

To identify risk factors for post-polypectomy bleeding (PPB), focusing on antithrombotic agents. This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. PPB occurred in 29 (3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210 (26.6%) patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB ( P < 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB ( P < 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants.

Risk of long-term anticoagulation under sustained severe arterial hypertension: A translational study comparing warfarin and the new oral anticoagulant apixaban

PubMed Central

Pfeilschifter, Waltraud; Steinstraesser, Thurid; Paulus, Patrick; Zeiner, Pia Susan; Bohmann, Ferdinand; Theisen, Alf; Lindhoff-Last, Edelgard; Penski, Cornelia; Wagner, Marlies; Mittelbronn, Michel

2016-01-01

New oral anticoagulants for the prevention of stroke and systemic embolism in patients with atrial fibrillation have recently been introduced. In this translational study, we explored the risk of long-term anticoagulation on intracerebral hemorrhage under sustained severe arterial hypertension. We initiated anticoagulation with warfarin or apixaban in spontaneously hypertensive rats prone to develop severe hypertension and subsequent intracerebral bleeding complications. A non-anticoagulated group served as control. During an 11-week-study period, blood pressure, anticoagulation parameters, and clinical status were determined regularly. The incidence of histopathologically proven intracerebral hemorrhage was defined as the primary endpoint. Both warfarin and apixaban anticoagulation was fairly stable during the study period, and all rats developed severe hypertension. Intracerebral hemorrhage was determined in 29% (4/14) of warfarin rats and in 10% (1/10) of apixaban rats. Controls did not show cerebral bleeding complications (chi-square not significant). Mortality rate at study termination was 33% (2/6) in controls, 43% (6/14) in the warfarin group, and 60% (6/10) in the apixaban group. Animals died from extracerebral complications in most cases. Our study describes an experimental intracerebral hemorrhage model in the context of sustained hypertension and long-term anticoagulation. Extracerebral bleeding complications occurred more often in warfarin-treated animals compared with apixaban and control rats. PMID:27189904

The role of oral anticoagulants in epistaxis.

PubMed

Buchberger, A M S; Baumann, A; Johnson, F; Peters, N; Piontek, G; Storck, K; Pickhard, A

2018-06-23

The purpose of this retrospective study was to identify the impact of oral anticoagulants on epistaxis with the focus on new oral anticoagulants. The study was conducted at the Department  for Ear- Nose- and Throat (ENT), Head and Neck Surgery, Technical University Munich, Germany. All patients presenting in 2014 with the diagnosis of epistaxis to a specialized ENT accident and emergency department were identified and analyzed in clinical data and medication. 600 adult cases, with a median age of 66.6 years were identified with active bleeding. 66.8% of all cases were anticoagulated. Classic oral anticoagulants (COAC) were three times more common in patients than new-generation oral anticoagulants (NOAC). Recurrent bleeding was significantly associated with oral anticoagulants (OAC) (p = 0.014) and bleeding location was most often anterior (p = 0.006). In contrast, severe cases, which required surgery or embolization were significantly more likely in non-anticoagulated middle-aged patients with posterior bleedings (p < 0.05). In our epistaxis cohort, OAC were highly overrepresented (40%) when compared to the general German population (1%) but COAC as well as NOAC played only a minor role in severe courses of epistaxis. Oral anticoagulation, especially with new-generation drugs, is not associated with more complicated and severe courses of epistaxis, but rather with recurrent bleeding. One should keep this information in mind when triaging the patient in the emergency room and when planning further procedures.

New horizons in anticoagulation: Direct oral anticoagulants and their implications in oral surgery

PubMed Central

Ripollés-de Ramón, Jorge; Collado-Yurrita, Luis; Vaello-Checa, Iris; Colmenero-Ruiz, Constantino; Helm, Alexandra; Ciudad-Cabañas, Maria-José; Serrano-Cuenca, Victoriano

2017-01-01

Background Thrombotic disorders remain a leading cause of death in the Western World. For decades, vitamin K antagonists used in the prevention of this pathology, such as warfarin or sintrom, were the only oral agents available for long-term anticoagulation, in spite of their disadvantages. Material and Methods An electronic database search was carried out on MedLine and The Cochrane Library Plus, without restrictions on the type of study nor dates, in English and Spanish. Abstracts were reviewed, and complete articles if necessary, considering all articles that included recommendations on DOACs and oral surgery. Results In recent years, the so-called “new oral anticoagulants” have been introduced in clinical practice to treat those patients whose medical conditions require long-term anticoagulant treatment, replacing traditional oral anticoagulants. Conclusions The new oral anticoagulants represent new therapeutic options, with a number of advantages such as poor interaction with food, minor drug interactions, and do not require periodic dose adjustments or routine controls. The purpose of this review is to establish an update on the new oral anticoagulants: Dabigatran, Rivarozaban, Apixaban and Edoxaban. Key words:Novel oral anticoagulants, Dabigatran, Rivaroxaban, Apixaban, Edoxaban, bleeding management, oral surgery, Anti-IIa, Anti Xa. PMID:28809374

[Clinical spectrum of patients with spontaneous retroperitoneal hematomas].

PubMed

Sánchez-González, Amada; Riancho-Zarrabeitia, Leyre; Salmón-González, Zaida; Riancho, José Antonio; Valero, Carmen

2015-10-05

Spontaneous retroperitoneal hematoma (SRH) is a potentially fatal clinical entity requiring immediate recognition and intervention. The clinical records of 18-year-old and older patients admitted to the University Hospital Marqués de Valdecilla from 2003 to 2013 were reviewed. "Spontaneous" was defined as unrelated to trauma, invasive procedures or bleeding due to aortic aneurysm rupture. Thirty-four patients with SRH (44% were on anticoagulant drugs). One-third of cases had chronic renal insufficiency. Abdominal pain was the most common symptom both in anticoagulated and non-anticoagulated patients (80% in anticoagulated and 89% in non-anticoagulated patients). About one half of the patients developed shock. A CT scan was the most commonly performed diagnostic test, followed by abdominal ultrasound. Most cases were managed conservatively (80%). More than half of the patients (66%) restarted anticoagulation therapy after the acute event with a mean delay of 19 days (range 2-90 days). None of them suffered a new bleeding episode. Restarting the anticoagulation treatment after hematoma resolution seems to be a safe practice. There is an increasing frequency of SRH in non-anticoagulated patients. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation in the primary prevention of ischemic stroke.

PubMed

Lightowlers, S; McGuire, A

1998-09-01

A number of clinical trials have shown the value of anticoagulating patients with nonrheumatic atrial fibrillation to prevent ischemic stroke. The purpose of this study was to assess the cost-effectiveness of anticoagulation in nonrheumatic atrial fibrillation with particular reference to the very elderly (aged >75 years) who have a higher incidence of bleeding events while undergoing anticoagulation. We calculated the incremental costs per life-year gained for 4 base cases using efficacy data from the Boston Area Anticoagulation Trial for Atrial Fibrillation, the meta-analysis of the 5 nonrheumatic atrial fibrillation trials, cost data from a district general hospital, and review of the literature. The cost per life-year gained free from stroke over 10 years ranged from -pound sterling 400.45 (ie, a resource saving achieved for each life-year gained free from stroke) to pound sterling 13,221.29. The results were most sensitive to alteration in the frequency of anticoagulation monitoring. For medical and economic reasons, anticoagulation treatment in the prevention of ischemic stroke is justified. Although older patients are more at risk of adverse events, anticoagulation is more cost-effective in this group.

Evaluation of the anticoagulant potential of polysaccharide-rich fractions extracted from macroalgae.

PubMed

Adrien, Amandine; Dufour, Delphine; Baudouin, Stanislas; Maugard, Thierry; Bridiau, Nicolas

2017-09-01

The aim of this study was to evaluate the potential anticoagulant activity of sulphated polysaccharide-containing extracts of six french edible marine macroalgae. Aqueous extracts of brown (Himanthalia elongata, Laminaria digitata, Ascophyllum nodosum, Fucus vesiculosus), green (Ulva lactuca) and red (Chondrus crispus) macroalgae were prepared and their biochemical properties were determined, including major biomolecules, sulphate and ash contents. The anticoagulant activity of each extract was investigated using different scales from the specific antithrombin-dependent pathway (anti-Xa and anti-IIa) to the intrinsic and/or common (Activated Partial Thromboplastin Time, APTT), extrinsic (Prothrombin Time, PT) or common (Thrombin Time, TT) anticoagulant pathways, and compared with those of commercial anticoagulants, heparin and Lovenox®. Laminaria digitata, Fucus vesiculosus and Chondrus crispus extracts showed a significant APTT anticoagulant capacity, only 5-fold lower than that of Lovenox®, which is a pure low molecular weight heparin used as an anticoagulant agent to prevent pulmonary embolism in patients undergoing surgery.

[Cataract surgery under topical anesthesia with oral anticoagulants].

PubMed

Wirbelauer, C; Weller, A; Häberle, H; Pham, D T

2004-09-01

Approximately 14 % of cataract surgery patients receive blood-thinning agents. In a prospective study, the influence of oral anticoagulants on intraoperative and postoperative hemorrhages in patients undergoing cataract surgery in topical anesthesia was investigated. 128 patients presenting for cataract surgery under oral anticoagulation were included. The mean preoperative prothrombin time was 39 +/- 18 %. Most patients (81 %) continued their oral anticoagulation (prothrombin time 34 +/- 13 %). All surgeries were performed in topical anesthesia. In 9 patients (7 %) an ocular hemorrhagic event was observed. These were not sight-threatening and resorbed spontaneously within a few days. Only one patient (0.8 %) had a slight hemorrhage in the anterior chamber. There were no differences (P > 0.05) between patients with or without hemorrhagic complications in the postoperative visual acuity, the intraocular pressure, the prothrombin time or the discontinuation of oral anticoagulants. Cataract surgery in topical anesthesia under oral anticoagulation did not increase the risk of sight-threatening hemorrhages. The continuation of oral anticoagulation seems particularly indicated for ambulatory cataract surgery.

What NPs need to know about anticoagulation therapy.

PubMed

Gay, Sarah E; Munaco, Sandra

2012-10-10

Venous thromboembolism (VTE) refers to pulmonary embolism and deep venous thrombosis. Anticoagulation is the cornerstone of management for patients with VTE. This review will discuss current anticoagulation guidelines.

Surgeon's guide to anticoagulant and antiplatelet medications part two: antiplatelet agents and perioperative management of long-term anticoagulation

PubMed Central

Yeung, Louise Y Y; Sarani, Babak; Weinberg, Jordan A; McBeth, Paul B; May, Addison K

2016-01-01

An increasing number of potent antiplatelet and anticoagulant medications are being used for the long-term management of cardiac, cerebrovascular, and peripheral vascular conditions. Management of these medications in the perioperative and peri-injury settings can be challenging for surgeons, mandating an understanding of these agents and the risks and benefits of various management strategies. In this two part review, agents commonly encountered by surgeons in the perioperative and peri-injury settings are discussed and management strategies for patients on long-term antiplatelet and anticoagulant therapy reviewed. In part one, we review warfarin and the new direct oral anticoagulants. In part two, we review antiplatelet agents and assessment of platelet function and the perioperative management of long-term anticoagulation and antiplatelet therapy. PMID:29767644

A surgeon's guide to anticoagulant and antiplatelet medications part one: warfarin and new direct oral anticoagulant medications

PubMed Central

McBeth, Paul B; Weinberg, Jordan A; Sarani, Babak; Yeung, Louise Y Y; May, Addison K

2016-01-01

An increasing number of potent antiplatelet and anticoagulant medications are being used for the long-term management of cardiac, cerebrovascular, and peripheral vascular conditions. Management of these medications in the perioperative and peri-injury settings can be challenging for surgeons, mandating an understanding of these agents and the risks and benefits of various management strategies. In this two-part review, agents commonly encounter by surgeons in the perioperative and peri-injury settings are discussed and management strategies for patients on long-term antiplatelet and anticoagulant therapy reviewed. In part I, we review warfarin and the new direct oral anticoagulants. In part II, we review antiplatelet agents and assessment of platelet function and the perioperative management of long-term anticoagulant and antiplatelet therapy. PMID:29767647

Left Atrial Appendage Closure Device With Delivery System: A Health Technology Assessment

PubMed Central

Nevis, Immaculate; Falk, Lindsey; Wells, David; Higgins, Caroline

2017-01-01

Background Atrial fibrillation is a common cardiac arrhythmia, and 15% to 20% of those who have experienced stroke have atrial fibrillation. Treatment options to prevent stroke in people with atrial fibrillation include pharmacological agents such as novel oral anticoagulants or nonpharmacological devices such as the left atrial appendage closure device with delivery system (LAAC device). The objectives of this health technology assessment were to assess the clinical effectiveness and cost-effectiveness of the LAAC device versus novel oral anticoagulants in patients without contraindications to oral anticoagulants and versus antiplatelet agents in patients with contraindications to oral anticoagulants. Methods We performed a systematic review and network meta-analysis. We also conducted an economic literature review, economic evaluation, and budget impact analysis to assess the cost-effectiveness and budget impact of the LAAC device compared with novel oral anticoagulants and oral antiplatelet agents (e.g., aspirin). We also spoke with patients to better understand their preferences, perspectives, and values. Results Seven randomized controlled studies met the inclusion criteria for indirect comparison. Five studies assessed the effectiveness of novel oral anticoagulants versus warfarin, and two studies compared the LAAC device with warfarin. No studies were identified that compared the LAAC device with aspirin in patients in whom oral anticoagulants were contraindicated. Using the random effects model, we found that the LAAC device was comparable to novel oral anticoagulants in reducing stroke (odds ratio [OR] 0.85; credible interval [Cr.I] 0.63–1.05). Similarly, the reduction in the risk of all-cause mortality was comparable between the LAAC device and novel oral anticoagulants (OR 0.71; Cr.I 0.49–1.22). The LAAC device was found to be superior to novel oral anticoagulants in preventing hemorrhagic stroke (OR 0.45; Cr.I 0.29–0.79), whereas novel oral anticoagulants were found to be superior to the LAAC device in preventing ischemic stroke (OR 0.67; Cr.I 0.24–1.64). The body of clinical evidence was found to be of moderate quality as assed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Results from the economic evaluation indicate that the LAAC device is cost-effective compared with aspirin in patients with contraindications to oral anticoagulants. In patients without contraindications to oral anticoagulants, we found that the LAAC device is not cost-effective compared with novel oral anticoagulants. Publicly funding the LAAC device in patients with nonvalvular atrial fibrillation with contraindications to oral anticoagulants could result in additional funding of $1.1 million to $7.7 million over the first five years. Patients interviewed reported on the impact of living with nonvalvular atrial fibrillation and were supportive of the LAAC device as a treatment option. Conclusions Moderate-quality evidence suggests that the LAAC device is as effective as novel oral anticoagulants in preventing stroke in people with nonvalvular atrial fibrillation. However, our results indicate that the LAAC device is cost-effective only in patients with contraindications to oral anticoagulants. People with nonvalvular atrial fibrillation with whom we spoke reported positive support for the LAAC device. PMID:28744335

Practical recommendations for the choice of anticoagulants in the management of patients with atrial fibrillation on ibrutinib.

PubMed

Chai, Khai Li; Rowan, Gail; Seymour, John F; Burbury, Kate; Carney, Dennis; Tam, Constantine S

2017-12-01

The management of AF represents a major challenge in patients with CLL, especially in elderly patients with multiple comorbidities who are representative of the majority of patients with CLL. This is especially complex in the case of ibrutinib. Many anticoagulants have potential for pharmacological interaction with ibrutinib, and ibrutinib itself has antiplatelet properties. Use of ibrutinib therapy in these patients mandates review and revision of the need for anticoagulation and best anticoagulant to use. Herein, we review the current knowledge of the metabolism of common anticoagulants and how they may interact with ibrutinib.

Satisfaction with oral anticoagulants in patients with atrial fibrillation

PubMed Central

Suárez Fernández, Carmen; Castilla-Guerra, Luis; Cantero Hinojosa, Jesus; Suriñach, Josep Maria; Acosta de Bilbao, Fernando; Tamarit, Juan José; Diaz Diaz, José Luis; Hernandez, Jose Luis; Pose, Antonio; Montero-Pérez-Barquero, Manuel; Roquer, Jaume; Gállego, Jaime; Vivancos, José; Mostaza, Jose María

2018-01-01

Background Although, by itself, atrial fibrillation is associated with an impairment of quality of life antithrombotic therapy may play a role. Objective To evaluate the satisfaction with anticoagulant treatment in patients with nonvalvular atrial fibrillation who attended internal medicine departments in Spain. Methods Patients from two different cross-sectional studies were combined. To measure the satisfaction with anticoagulant treatment, the Anti-Clot-Treatment Scale (ACTS) questionnaire was completed by every patient. A multivariate analysis was performed to determine the variables associated with satisfaction of patients receiving oral anticoagulants. Results A total of 1,309 patients (mean age 78.5±8.4 years; 49.3% men; CHA2DS2VASC 4.9±1.5; HAS-BLED 2.0±0.9) were included in the study, of whom 902 (68.9%) were taking vitamin K antagonists (VKA) and 407 (31.1%) direct oral anticoagulants (DOACs). Overall, satisfaction with oral anticoagulation was high (ACTS Burdens scale 49.69±9.45; ACTS Benefits scale 11.35±2.61). The perceived burdens with anticoagulant treatment were lower in men, as well as in patients with no dependency, normal renal function, who were not polymedicated, or who had moderate bleeding risk. Among patients taking VKA, those subjects with a lower number of International Normalized Ratio (INR) determinations in the last 6 months or with an optimal time in the therapeutic range exhibited a lower perceived burden. Patients taking DOACs (vs VKA) showed a lower perceived burden with anticoagulation. Benefits with anti-coagulation were higher in men, younger patients, those with no dependency, or low bleeding risk. Perceived benefits were higher in patients taking DOACs (vs VKA). Conclusion Satisfaction with oral anticoagulation was high in patients with nonvalvular atrial fibrillation, who were attending internal medicine departments daily in Spain. Among patients taking VKA, those subjects with a lower number of INR determinations in the last 6 months or with an optimal time in the therapeutic range exhibited a lower perceived burden with anticoagulant therapy. Patients taking DOACs (vs VKA) showed lower perceived burdens and higher perceived benefits with anticoagulation. PMID:29497282

A new instrument for measuring anticoagulation-related quality of life: development and preliminary validation

PubMed Central

Samsa, Greg; Matchar, David B; Dolor, Rowena J; Wiklund, Ingela; Hedner, Ewa; Wygant, Gail; Hauch, Ole; Marple, Cheryl Beadle; Edwards, Roger

2004-01-01

Background Anticoagulation can reduce quality of life, and different models of anticoagulation management might have different impacts on satisfaction with this component of medical care. Yet, to our knowledge, there are no scales measuring quality of life and satisfaction with anticoagulation that can be generalized across different models of anticoagulation management. We describe the development and preliminary validation of such an instrument – the Duke Anticoagulation Satisfaction Scale (DASS). Methods The DASS is a 25-item scale addressing the (a) negative impacts of anticoagulation (limitations, hassles and burdens); and (b) positive impacts of anticoagulation (confidence, reassurance, satisfaction). Each item has 7 possible responses. The DASS was administered to 262 patients currently receiving oral anticoagulation. Scales measuring generic quality of life, satisfaction with medical care, and tendency to provide socially desirable responses were also administered. Statistical analysis included assessment of item variability, internal consistency (Cronbach's alpha), scale structure (factor analysis), and correlations between the DASS and demographic variables, clinical characteristics, and scores on the above scales. A follow-up study of 105 additional patients assessed test-retest reliability. Results 220 subjects answered all items. Ceiling and floor effects were modest, and 25 of the 27 proposed items grouped into 2 factors (positive impacts, negative impacts, this latter factor being potentially subdivided into limitations versus hassles and burdens). Each factor had a high degree of internal consistency (Cronbach's alpha 0.78–0.91). The limitations and hassles factors consistently correlated with the SF-36 scales measuring generic quality of life, while the positive psychological impact scale correlated with age and time on anticoagulation. The intra-class correlation coefficient for test-retest reliability was 0.80. Conclusions The DASS has demonstrated reasonable psychometric properties to date. Further validation is ongoing. To the degree that dissatisfaction with anticoagulation leads to decreased adherence, poorer INR control, and poor clinical outcomes, the DASS has the potential to help identify reasons for dissatisfaction (and positive satisfaction), and thus help to develop interventions to break this cycle. As an instrument designed to be applicable across multiple models of anticoagulation management, the DASS could be crucial in the scientific comparison between those models of care. PMID:15132746

Heparin bridge therapy and post-polypectomy bleeding

PubMed Central

Kubo, Toshiyuki; Yamashita, Kentaro; Onodera, Kei; Iida, Tomoya; Arimura, Yoshiaki; Nojima, Masanori; Nakase, Hiroshi

2016-01-01

AIM To identify risk factors for post-polypectomy bleeding (PPB), focusing on antithrombotic agents. METHODS This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. RESULTS PPB occurred in 29 (3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210 (26.6%) patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB (P < 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB (P < 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. CONCLUSION Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants. PMID:28018108

Optical profiling of anticoagulation status (Conference Presentation)

NASA Astrophysics Data System (ADS)

Tshikudi, Diane M.; Tripathi, Markandey M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.

2016-02-01

Defective blood coagulation resulting from excessive procoagulant activity often leads to thrombotic disorders such as stroke and myocardial infarction. A variety of oral and injectable anticoagulant drugs are prescribed to prevent or treat life-threatening thrombosis. However, due to bleeding complications often associated with anticoagulant treatment, routine monitoring and accurate dosing of anticoagulant therapy is imperative. We have developed Optical thromboelastography (OTEG), a non-contact approach that utilizes a drop of whole blood to measure blood coagulation status in patients. Here, we demonstrate the capability of OTEG for rapidly monitoring anticoagulation in whole blood samples. OTEG monitors coagulation status by assessing changes in blood viscosity from temporal intensity fluctuations of laser speckle patterns during clotting. In OTEG a blood drop is illuminated with coherent light and the blood viscosity is measured from the speckle intensity autocorrelation curve, g2 (t). The metrics, clotting time (R+k), clot progression (angle) and maximum clot stiffness (MA) are then extracted. The aim of the current study was to evaluate the accuracy of OTEG in assessing anticoagulation status of common anticoagulants including heparin, argatroban and rivaroxaban status. A dose-dependent prolongation of R+k was observed in anticoagulated blood, which closely corresponded with standard-reference Thromboelastography (TEG) (r 0.87-0.99, P>0.01 for all cases). OTEG angle was unaltered by anticoagulation whereas TEG angle presented a dose-dependent diminution probably linked to clot rupture. In both OTEG and TEG, MA was unaffected by heparin, argatroban or rivaroxaban. We conclude that OTEG can accurately monitor anticoagulation status following treatment, potentially providing a powerful tool for routine monitoring of patients in the doctor's office or in the home setting.

Anticoagulation in pregnant women with mechanical heart valve prostheses

PubMed Central

Meschengieser, S; Fondevila, C; Santarelli, M; Lazzari, M

1999-01-01

OBJECTIVE—To evaluate the outcome of pregnancy in women with mechanical heart valve prostheses in relation to the anticoagulant treatment used in the first trimester and the incidence of thrombotic and bleeding complications.
METHODS—92 pregnancies in 59 women were followed between 1986 and 1997. In 31 pregnancies, oral anticoagulants were discontinued when pregnancy was diagnosed and subcutaneous heparin was started (12 500 U every 12 hours) adjusted to prolong the adjusted partial thromboplastin time to twice the control level. In the second trimester oral anticoagulants were resumed but changed to heparin again 15 days before the expected delivery date. In 61 pregnancies oral anticoagulants were continued during the first trimester. The same regimen of heparin was used for delivery.
RESULTS—Abortion or fetal losses were similar (p = 0.5717) in women exposed to oral anticoagulants in the first trimester (13/61; 25%) compared with those who received adjusted subcutaneous heparin (6/31; 19%). Embolic episodes were more common (p = 0.0029) in women who received heparin (4.92%) compared with those on oral anticoagulants (0.33%). Embolic episodes were cerebral and transient. No valve thromboses were observed. No malformations appeared in the 71 newborns, except for one case of hydrocephalus. There were no maternal deaths secondary to thrombotic complications. The only death was the result of major bleeding after the delivery of a premature stillborn.
CONCLUSIONS—Oral anticoagulants seem to be safer for the mother than adjusted subcutaneous heparin. Heparin does not offer a clear advantage over oral anticoagulation in the pregnancy outcome.


Keywords: pregnancy; oral anticoagulants; heparin; prosthetic valves PMID:10377303

Impact of non-anticoagulant therapy on patients with sepsis-induced disseminated intravascular coagulation: A multicenter, case-control study.

PubMed

Kudo, Daisuke; Hayakawa, Mineji; Ono, Kota; Yamakawa, Kazuma

2018-03-01

Anticoagulant therapy for patients with sepsis is not recommended in the latest Surviving Sepsis Campaign guidelines, and non-anticoagulant therapy is the global standard treatment approach at present. We aimed at elucidating the effect of non-anticoagulant therapy on patients with sepsis-induced disseminated intravascular coagulation (DIC), as evidence on this topic has remained inconclusive. Data from 3195 consecutive adult patients admitted to 42 intensive care units for the treatment of severe sepsis were retrospectively analyzed via propensity score analyses with and without multiple imputation. The primary outcome was in-hospital all-cause mortality. Among 1784 patients with sepsis-induced DIC, 745 (41.8%) were not treated with anticoagulants. The inverse probability of treatment-weighted (with and without multiple imputation) and quintile-stratified propensity score analyses (without multiple imputation) indicated a significant association between non-anticoagulant therapy and higher in-hospital all-cause mortality (odds ratio [95% confidence interval]: 1.59 [1.19-2.12], 1.32 [1.02-1.81], and 1.32 [1.03-1.69], respectively). However, quintile-stratified propensity score analyses with multiple imputation and propensity score matching analysis with and without multiple imputation did not show this association. Survival duration was not significantly different between patients in the propensity score-matched non-anticoagulant therapy group and those in the anticoagulant therapy group (Cox regression analysis with and without multiple imputation: hazard ratio [95% confidence interval]: 1.26 [1.00-1.60] and 1.22 [0.93-1.59], respectively). It remains controversial if non-anticoagulant therapy is harmful, equivalent, or beneficial compared with anticoagulant therapy in the treatment of patients with sepsis-induced DIC. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinicians-related Determinants of Anticoagulation Therapy and Prophylaxis in Nigeria

PubMed Central

Anakwue, Raphael; Nwagha, Theresa; Ukpabi, Ogba J.; Obeka, Ndudim; Onwubuya, Emmanuel; Onwuchekwa, Uwa; Azubuike, Benjamin; Okoye, Innocent

2017-01-01

Background: Thromboembolic and hypercoagulable diseases are common life-threatening but treatable problems in hospital practice. Fortunately, anticoagulation is an efficacious management practice indicated for arterial, venous, and intracardiac thromboembolism. Clinicians in developing countries may have gaps in their knowledge of anticoagulation therapy/prophylaxis which could affect their clinical decision. Objectives: The study examined the knowledge and attitude of clinicians to anticoagulation therapy/prophylaxis in some tertiary hospitals in Nigeria. Methodology: The study was a multicenter survey. A pretested questionnaire was administered to clinicians in six tertiary hospitals in Southeast Nigeria. Results: A total of 528 questionnaires were returned by 419 (79.4%) residents and 109 (20.6%) consultants. We observed significant abysmal knowledge and lack of awareness of direct oral anticoagulants (DOACs) among most respondents irrespective of their job grades (P = 0.02, odds ratio [OR] 0.59, 95% confidence interval [CI] 0.38–0.90). Their knowledge of anti-Xa assay as laboratory monitoring tool was also significantly inadequate (P = 0.001, OR 0.23, 95% CI 0.10–0.51). On statement analysis on their attitude to anticoagulation therapy/prophylaxis, “Do you think anticoagulation therapy/prophylaxis is clinically relevant” had the highest mean of 4.60, P = 0.01, and a high degree of agreement; while “Should hospital inpatient with > 3 days admission routinely receive anticoagulation/prophylaxis?” had the lowest mean of 2.27, P = 0.02, and a low degree of agreement. Conclusion: There is the need to upscale knowledge of anticoagulation agents and an attitude change to anticoagulation therapy/prophylaxis, especially on the DOACs through continuing medical education activities in emerging countries such as Nigeria. PMID:29063899

Differentiation of parenteral anticoagulants in the prevention and treatment of venous thromboembolism.

PubMed

Fareed, Jawed; Adiguzel, Cafer; Thethi, Indermohan

2011-03-28

The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available. MEDLINE and EMBASE databases were searched to identify relevant original articles. Low-molecular-weight heparins have nearly replaced unfractionated heparin as the gold standard antithrombotic agent. Low-molecular-weight heparins currently available in the US are enoxaparin, dalteparin, and tinzaparin. Each low-molecular-weight heparin is a distinct pharmacological entity with different licensed indications and available clinical evidence. Enoxaparin is the only low-molecular-weight heparin that is licensed for both venous thromboembolism prophylaxis and treatment. Enoxaparin also has the largest body of clinical evidence supporting its use across the spectrum of venous thromboembolism management and has been used as the reference standard comparator anticoagulant in trials of new anticoagulants. As well as novel oral anticoagulant agents, biosimilar and/or generic low-molecular-weight heparins are now commercially available. Despite similar anticoagulant properties, studies report differences between the branded and biosimilar and/or generic agents and further clinical studies are required to support the use of biosimilar low-molecular-weight heparins. The newer parenteral anticoagulant, fondaparinux, is now also licensed for venous thromboembolism prophylaxis in surgical patients and the treatment of acute deep-vein thrombosis; clinical experience with this anticoagulant is expanding. Parenteral anticoagulants should be prescribed in accordance with recommended dose regimens for each clinical indication, based on the available clinical evidence for each agent to assure optimal safety and efficacy.

75 FR 67088 - Clean Water Act (CWA) and Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Common...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-01

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2010-0818; FRL-9218-6] Clean Water Act (CWA) and... solicit input on methods being evaluated by the Office of Pesticide Programs (OPP) and the Office of Water (OW), with the support of the Office of Research and Development (ORD) to develop common...

A comparison of two rodent repellents in broadcast seeding Douglas-fir.

Treesearch

Edward J. Dimock

1957-01-01

Broadcast seeding of cutover lands is a promising, yet still problematical, means of tree regeneration. Substantial progress has been made since 1950, particularly with the introduction of new rodenticides and repellents suitable for direct application to the seed. One of these is tetramine (tetramethylene disulpho tetramine), a highly lethal repellent that has shown...

Frequently Asked Questions

Science.gov Websites

and pets? Can I apply DEET under my clothes? Return to Top Animals How can I protect my pets when (rodenticides) hurt kids and pets? Could snail bait hurt my dog? Return to Top Environment What should I do when ? Is 'food grade' diatomaceous earth okay for pest control? What does it mean when food is organic

75 FR 69658 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-15

... Activities; Submission to OMB for Review and Approval; Comment Request; Experimental Use Permits (EUPs) for... activity. An Agency may not conduct or sponsor, and a person is not required to respond to, a collection of... instrument or form, if applicable. Abstract: The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA...

To amend the Federal Insecticide, Fungicide, and Rodenticide Act to increase the availability of pesticides for the management of parasitic pests that adversely impact the health of managed pollinator bees, and for other purposes.

THOMAS, 113th Congress

Rep. Scott, Austin [R-GA-8

2014-09-10

House - 09/22/2014 Referred to the Subcommittee on Horticulture, Research, Biotechnology, and Foreign Agriculture. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

U.S. EPA, Pesticide Product Label, GOPHACIDE 0.1% BAIT (RODENTICIDE), 09/11/1972

EPA Pesticide Factsheets

2011-04-21

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78 FR 57388 - Product Cancellation Order for Certain Pesticide Registrations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-18

... Insecticide, Fungicide, and Rodenticide Act (FIFRA). This cancellation order follows a May 29, 2013 Federal... cancellation for the end use products listed in Table 2 of Unit II., will be effective December 31, 2016. FOR... products in Tables 1 and 2 of this unit, in sequence by EPA company number. This number corresponds to the...

76 FR 53942 - Notice of Lodging of First Addendum to Consent Decree Under the Emergency Planning and Community...

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2011-08-30

... DEPARTMENT OF JUSTICE Notice of Lodging of First Addendum to Consent Decree Under the Emergency Planning and Community Right-To-Know Act, the Clean Water Act, the Resource Conservation and Recovery Act, the Federal Insecticide, Fungicide, and Rodenticide Act, the Comprehensive Environmental Response, Compensation, and Liability Act, the Safe...

Direct oral anticoagulants: An update.

PubMed

Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

2017-12-30

Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

The Best Anticoagulation Therapy in Multiple-Trauma Patients with Mechanical Heart Valves: Evaluation of Latest Guidelines and Studies.

PubMed

Moeinipour, Aliasghar; Zarifian, Ahmadreza; Sheikh Andalibi, Mohammad Sobhan; Shamloo, Alireza Sepehri; Ahmadabadi, Ali; Amouzeshi, Ahmad; Hoseinikhah, Hamid

2015-12-22

It is common practice for patients with prosthetic cardiac devices, especially heart valve prosthesis, arterial stents, defibrillators, and pacemaker devices, to use anticoagulation treatment. When these patients suffer from multiple trauma after motor vehicle accidents, the best medical management for this challenging position is mandatory. This strategy should include a rapid diagnosis of all possible multiple organ injuries, with special attention to anticoagulation therapy so as to minimize the risk of thromboembolism complication in prosthetic devices. In this review, we describe the best medical management for patients with multiple trauma who use anticoagulants after heart valve replacement. We searched electronic databases PubMed/Medline, Scopus, Embase, and Google Scholar using the following terms: anticoagulant, warfarin, heparin, and multiple trauma. Also, similar studies suggested by the databases were included. Non-English articles were excluded from the review. For patients who use anticoagulation therapy, teamwork between cardiac surgeons, general surgeons, anesthesiologists, and cardiologists is essential. For optimal medical management, multiple consults between members of this team is mandatory for rapid diagnosis of all possible damaged organs, with special attention to the central nervous system, chest, and abdominal traumas. With this strategy, it is important to take note of anticoagulation drugs to minimize the risk of thromboembolism complications in cardiac devices. The best anticoagulant agents for emergency operations in patients with multiple trauma who are using an anticoagulant after heart valve replacement are fresh frozen plasma (FFP) and prothrombin complex concentrates (PCC).

[Anticoagulation in polypathological patients with atrial fibrillation].

PubMed

Díez-Manglano, Jesús; Bernabeu-Wittel, Máximo; Barón-Franco, Bosco; Murcia-Zaragoza, José; Fuertes Martín, Aurelio; Alemán, Antonio; Ollero-Baturone, Manuel

2013-02-02

To determine the use of oral anticoagulants in polypathological patients with atrial fibrillation and its influence on mortality and loss of functionality. Patients with polypathological patient criteria and atrial fibrillation were included in an observational, prospective and multicenter study. Data on demographic, clinical, functional and sociofamilial characteristics, CHADS2 score, levels of hemoglobin, albumin and creatinine, use of oral anticoagulants and survival and functional status at one year were collected. Five hundred and thirty-two (32.6%) of 1,632 polypathological patients had atrial fibrillation. The stroke risk was high in 505 (94.9%), moderate in 24 (4.5%) and low in 3 (0.6%) patients. Oral anticoagulants were used in 61% of patients with CHADS2 score≥2 and in 37.5% with CHADS2 score=1. Oral anticoagulants were less used in older patients, with more functional and cognitive impairment. Heart failure was associated with more use of oral anticoagulants. There was no difference by the presence of hypertension, diabetes, anemia, renal insufficiency or stroke. In multivariate analysis the use of oral anticoagulants was independently associated with lower age, lower cognitive impairment, absence of hepatic disease and with higher stroke risk. The prescription of oral anticoagulants was independently associated with more survival at one year with no influence on functional status. Oral anticoagulants are underused in polypathological patients with atrial fibrillation despite being associated with more survival. Copyright © 2012 Elsevier España, S.L. All rights reserved.

An overview of existing raptor contaminant monitoring activities in Europe.

PubMed

Gómez-Ramírez, P; Shore, R F; van den Brink, N W; van Hattum, B; Bustnes, J O; Duke, G; Fritsch, C; García-Fernández, A J; Helander, B O; Jaspers, V; Krone, O; Martínez-López, E; Mateo, R; Movalli, P; Sonne, C

2014-06-01

Biomonitoring using raptors as sentinels can provide early warning of the potential impacts of contaminants on humans and the environment and also a means of tracking the success of associated mitigation measures. Examples include detection of heavy metal-induced immune system impairment, PCB-induced altered reproductive impacts, and toxicity associated with lead in shot game. Authorisation of such releases and implementation of mitigation is now increasingly delivered through EU-wide directives but there is little established pan-European monitoring to quantify outcomes. We investigated the potential for EU-wide coordinated contaminant monitoring using raptors as sentinels. We did this using a questionnaire to ascertain the current scale of national activity across 44 European countries. According to this survey, there have been 52 different contaminant monitoring schemes with raptors over the last 50years. There were active schemes in 15 (predominantly western European) countries and 23 schemes have been running for >20years; most monitoring was conducted for >5years. Legacy persistent organic compounds (specifically organochlorine insecticides and PCBs), and metals/metalloids were monitored in most of the 15 countries. Fungicides, flame retardants and anticoagulant rodenticides were also relatively frequently monitored (each in at least 6 countries). Common buzzard (Buteo buteo), common kestrel (Falco tinnunculus), golden eagle (Aquila chrysaetos), white-tailed sea eagle (Haliaeetus albicilla), peregrine falcon (Falco peregrinus), tawny owl (Strix aluco) and barn owl (Tyto alba) were most commonly monitored (each in 6-10 countries). Feathers and eggs were most widely analysed although many schemes also analysed body tissues. Our study reveals an existing capability across multiple European countries for contaminant monitoring using raptors. However, coordination between existing schemes and expansion of monitoring into Eastern Europe is needed. This would enable assessment of the appropriateness of the EU-regulation of substances that are hazardous to humans and the environment, the effectiveness of EU level mitigation policies, and identify pan-European spatial and temporal trends in current and emerging contaminants of concern. Copyright © 2014. Published by Elsevier Ltd.

Fall risk and anticoagulation for atrial fibrillation in the elderly: A delicate balance.

PubMed

Hagerty, Tracy; Rich, Michael W

2017-01-01

Guidelines for managing atrial fibrillation recommend systemic anticoagulation for almost all patients age 65 and older, but in practice up to 50% of older patients do not receive maintenance anticoagulation therapy. The most common reason physicians cite for withholding anticoagulation in older patients with atrial fibrillation is a perception of a high risk of falling and associated bleeding, especially intracranial hemorrhage. Copyright © 2017 Cleveland Clinic.

Efficacy of vitamin E-bonded polysulfone dialyzer and polysulfone dialyzer on a series of non-anticoagulant hemodialysis.

PubMed

Torato, Toshihiro; Doi, Kent; Negishi, Kousuke; Hamasaki, Yoshifumi; Satonaka, Hiroshi; Hanafusa, Norio; Noiri, Eisei

2013-01-01

Non-anticoagulant hemodialysis is conducted occasionally at limited numbers of hospitals on an empirical basis. This study examines the efficacy of polysulfone and vitamin E-bonded polysulfone dialyzer for non-anticoagulant hemodialysis. These dialyzers were assigned one after the other for a vintage hemodialysis patient complicated with uncontrollable bleeding. The patient's vital and console data throughout non-anticoagulant hemodialysis were monitored serially. Both dialyzers were reasonably applicable to hemodialysis without major clotting. The scheduled treatment period was completed. Vitamin E-bonded polysulfone dialyzer was superior to non-anticoagulant hemodialysis based on venous pressure observed during treatment.

Athletes and blood clots: individualized, intermittent anticoagulation management.

PubMed

Berkowitz, J N; Moll, S

2017-06-01

Essentials Athletes on anticoagulants are typically prohibited from participation in contact sports. Short-acting anticoagulants allow for reconsideration of this precedent. An individualized pharmacokinetic/pharmacodynamics study can aid patient-specific management. Many challenges and unresolved issues exist regarding such tailored intermittent dosing. Athletes with venous thromboembolism (VTE) are typically prohibited from participating in contact sports during anticoagulation therapy, but such mandatory removal from competition can cause psychological and financial detriments for athletes and overlooks patient autonomy. The precedent of compulsory removal developed when options for anticoagulation therapy were more limited, but medical advances now allow for rethinking of the management of athletes with VTE. We propose a novel therapeutic approach to the treatment of athletes who participate in contact sports and require anticoagulation. A personalized pharmacokinetic/pharmacodynamics study of a direct oral anticoagulant can be performed for an athlete, which can inform the timing of medication dosing. Managed carefully, this can allow athletic participation when plasma drug concentration is minimal (minimizing bleeding risk) and prompt resumption of treatment after the risk of bleeding sufficiently normalizes (maximizing therapeutic time). © 2017 International Society on Thrombosis and Haemostasis.

Pathology consultation on anticoagulation monitoring: factor X-related assays.

PubMed

Wool, Geoffrey D; Lu, Chuanyi M

2013-11-01

To review various anticoagulation therapies and related laboratory monitoring issues, with a focus on factor X-related chromogenic assays. A case-based approach is used to review pertinent published literatures and product inserts of anticoagulation drugs and to look back on clinical use of factor X-related chromogenic assays. The number of anticoagulants available to clinicians has increased greatly in the past decade. Whether and how these anticoagulants should be monitored are areas of uncertainty for clinicians, which can lead to misuse of laboratory assays and suboptimal patient management. Factor X-related assays are of particular concern because of the similar and often confusing test names. Based on a common clinical case scenario and literature review regarding anticoagulant monitoring, an up-to-date discussion and review of the various factor X-related assays are provided, focusing on the differences in test designs and clinical utilities between the chromogenic anti-Xa and chromogenic factor X activity assays. Anticoagulation therapy and related laboratory monitoring are rapidly evolving areas of clinical practices. A good knowledge of relevant laboratory assays and their clinical applications is necessary to help optimize patient care.

[Treatment with inhibitors of new oral direct anticoagulants in patients with severe bleedings or urgent surgical procedures. The new dabigatran antidote: the place of idarucizumab in clinical practice].

PubMed

Boda, Zoltán

2016-03-20

Only vitamin K antagonists could be applied as oral anticoagulants over the past six decades. Coumarols have narrow therapeutic range, and unpredictable anticoagulant effects are resulted by multiple drug interactions. Therefore, regular routine monitoring of the international normalized ratio is necessary. There are two groups of factor-specific anticoagulants: molecules with anti-FIIa (dabigatran) and anti-FXa (rivaroxaban, apixaban and edoxaban) effect. Author summarizes the most important clinical features of the new oral anticoagulants, their indications and the possibilities of laboratory controls. Bleedings are the most important side effects of anticoagulants. This review summarizes the current published evidences for new oral anticoagulants reversal (non-specific and specific) agents, especially in cases with severe acute bleedings or urgent surgery procedures. It reports on how to use inhibitors, the recommended doses and the most important clinical results. The review focuses on idarucizumab - already approved by the U.S. Food and Drug Administration and the European Medicines Agency - which has a key role as the first specific inhibitor of dabigatran.

Anticoagulation in Cardiobacterium hominis Prosthetic Valve Endocarditis in a Patient with Hypercoagulability: A Clinical Dilemma.

PubMed

Mamdani, Natasha; Shah, Jatan; Simms, Michael

2017-02-01

Cardiobacterium hominis is an uncommon cause of prosthetic valve endocarditis (PVE) and often presents insidiously. In comparison, prosthetic valve thrombosis (PVT) is a rare, but life-threatening condition that commonly occurs due to inadequate anticoagulation. Anticoagulation is relatively contraindicated in patients with endocarditis as it may prove to be lethal due to increased risk of cerebral hemorrhage. However, anticoagulation is required in patients with PVT, or for its prevention. We present a case of a 35-year-old male with a history of hypercoagulability and St. Jude's aortic valve on warfarin, who presented with chest pain andwas found to have a mass on the aorticvalve, with blood cultures revealing C. hominis.The patient was treated with appropriate antibiotics and anticoagulation was continued. No neurological complications were noted during the treatment period. This case demonstrates that carefully weighing the risks and benefits of continuing anticoagulation is essential in preventing poor outcomes.

Anticoagulation management associated with extracorporeal circulation.

PubMed

Sniecinski, Roman M; Levy, Jerrold H

2015-06-01

The use of extracorporeal circulation requires anticoagulation to maintain blood fluidity throughout the circuit, and to prevent thrombotic complications. Additionally, adequate suppression of hemostatic activation avoids the unnecessary consumption of coagulation factors caused by the contact of blood with foreign surfaces. Cardiopulmonary bypass represents the greatest challenge in this regard, necessitating profound levels of anticoagulation during its conduct, but also quick, efficient reversal of this state once the surgical procedure is completed. Although extracorporeal circulation has been around for more than half a century, many questions remain regarding how to best achieve anticoagulation for it. Although unfractionated heparin is the predominant agent used for cardiopulmonary bypass, the amount required and how best to monitor its effects are still unresolved. This review discusses the use of heparin, novel anticoagulants, and the monitoring of anticoagulation during the conduct of cardiopulmonary bypass. Copyright © 2015 Elsevier Ltd. All rights reserved.

Catheter-related thrombosis: biological and clinical evidence for risk with currently available anticoagulants.

PubMed

Montalescot, Gilles; Walenga, Jeanine M

2009-01-01

Anticoagulants used during percutaneous coronary intervention (PCI) should not only prevent coronary events, but also minimize the risk of periprocedural complications. Current anticoagulation therapies for PCI include unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin. UFH and enoxaparin have good efficacy and safety profiles in PCI; furthermore, associated periprocedural complications such as catheter thrombosis are rare. Although newer anticoagulants seem safe and effective in patients with acute coronary syndrome, clinical trial data suggest that some pure factor Xa (FXa) inhibitors are associated with increased rates of catheter thrombosis, compared with heparin-based agents. Experimental systems show that polytherapeutic agents, including UFH and enoxaparin, are more effective anticoagulants than certain single-target agents. More studies are needed to assess whether catheter thrombosis is a class-, drug-, or dose-related effect, and how best to prevent it. Future trials should report the rates of periprocedural complications when assessing the safety of novel anticoagulation therapies in PCI.

Sustained impact of anticoagulant control achieved in an anticoagulation management service after transfer of management to the primary care physician.

PubMed

Bungard, Tammy J; Ritchie, Bruce; Garg, Sipi; Tsuyuki, Ross T

2012-02-01

To determine whether the impact of anticoagulant control achieved in an Anticoagulation Management Service (AMS) is sustained after transfer of anticoagulation management to the primary care physician (PCP), and to assess patient satisfaction with their anticoagulation management by both the AMS and PCP. Prospective, randomized trial. Pharmacist-directed ambulatory AMS located in a tertiary medical care facility and PCP practices in Canada. Sixty-two adults who had received at least 6 months of warfarin therapy managed by the AMS. Patients were randomly assigned to remain with AMS care (32 patients) or to transfer their anticoagulation management care to their PCP (30 patients). After 4.5 months of care, patients in both groups completed a validated survey instrument assessing their satisfaction with the management of their warfarin therapy. Of 295 patients screened, most were excluded from the study for denying consent or for having previous bleeding or clotting complications while taking warfarin. Patients in the AMS and PCP groups who completed the study were similar in age (median 70 and 76 yrs, respectively), and most had atrial fibrillation as an indication for warfarin (75% and 83%, respectively). The primary outcome measure-mean percentage of time within the desired international normalized ratio (INR) range after 6 months-was compared between the two groups, using both the actual range (INR 2.5 ± 0.5) and an expanded range (INR 2.5 ± 0.7). No significant difference was noted in this outcome between the groups (73.5 ± 19.1% vs 76.9 ± 24.5% for the AMS vs PCP groups, p=0.54). Other outcome measures were rates of thrombotic and hemorrhagic events resulting in emergency department visits or hospitalizations, patients' overall satisfaction with warfarin therapy, and patients' preferred anticoagulation management strategy. Two hemorrhagic events and one thrombotic event occurred in each group. Patients were more satisfied with their anticoagulant management by the AMS relative to PCP care (p=0.01), and given the choice, patients preferred AMS care (p=0.001). During this 6-month trial, anticoagulation control did not significantly differ between patients who continued to receive anticoagulation management by the AMS and those who transferred to their PCP for anticoagulation management, indicating that the effects of AMS care were sustained. Although patients were more satisfied and preferred to stay with AMS care, this study shows that select patients could have their anticoagulation care transferred to their PCP without compromising anticoagulation control. © 2012 Pharmacotherapy Publications, Inc.

Anticoagulation knowledge in patients with atrial fibrillation: An Australian survey.

PubMed

Obamiro, Kehinde O; Chalmers, Leanne; Lee, Kenneth; Bereznicki, Bonnie J; Bereznicki, Luke R E

2018-03-01

Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia in clinical practice, and is associated with a significant medical and economic burden. Anticoagulants reduce the risk of stroke and systemic embolism by approximately two-thirds compared with no therapy. Knowledge regarding anticoagulant therapy can influence treatment outcomes in patients with AF. To measure the level of anticoagulation knowledge in patients with AF taking oral anticoagulants (OACs), investigate the association between patient-related factors and anticoagulation knowledge, and compare these results in patients taking warfarin and direct-acting oral anticoagulant (DOACs). Participants were recruited for an online survey via Facebook. Survey components included the Anticoagulation Knowledge Tool, the Perception of Anticoagulant Treatment Questionnaires (assessing treatment expectations, convenience and satisfaction), a modified Cancer Information Overload scale and the Morisky Medication Adherence Scale. Treatment groups were compared and predictors of OAC knowledge were identified. Participants taking warfarin had a higher knowledge score compared with those taking DOACs (n = 386, 73% ± 13% vs 66% ± 14%, P<.001). Advancing age, type of OAC, health information overload and ease of OAC use (treatment expectation) were significant predictors of knowledge. Treatment expectation, including the belief that OAC treatment would cause bleeding side effects, varied significantly between participants taking warfarin and DOACs (P = .011). The study identified knowledge gaps in patients taking OACs, and these deficiencies appeared to be greater in participants taking DOACs. Knowledge assessment should be integrated into patient counselling sessions to help identify and resolve knowledge deficits. © 2018 John Wiley & Sons Ltd.

Acute management of bleeding in patients on novel oral anticoagulants.

PubMed

Siegal, Deborah M; Crowther, Mark A

2013-02-01

Novel oral anticoagulants that directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are currently available for prevention of venous thromboembolism (VTE) after orthopaedic surgery, treatment of acute VTE, and prevention of arterial thromboembolism in non-valvular atrial fibrillation. These agents offer advantages over VKAs, including rapid onset, shorter half-lives, fewer drug interactions, and lack of need for routine monitoring. However, there are no established agents to reverse their anticoagulant effect. We review the risk of bleeding with the novel oral anticoagulants and the limitations of conventional coagulation assays for measuring anticoagulant effect. We provide an approach to the management of patients with bleeding complications with evidence for various interventions for reversal, where available.

Impact of a pharmacist-led warfarin self-management program on quality of life and anticoagulation control: a randomized trial.

PubMed

Verret, Lucie; Couturier, Justine; Rozon, Andréanne; Saudrais-Janecek, Sarah; St-Onge, Amélie; Nguyen, Angela; Basmadjian, Arsène; Tremblay, Simon; Brouillette, Denis; de Denus, Simon

2012-10-01

To evaluate the impact of a pharmacist-led warfarin patient self-management program on quality of life and anticoagulation control compared with management in a physician-led specialized anticoagulation clinic. Prospective, randomized, controlled, open-label trial. Tertiary care academic medical center. A total of 114 patients aged 18-75 years who were followed at a specialized anticoagulation clinic, had received warfarin for at least 6 months, and were expected to continue warfarin for a minimum of 4 months. All patients attended an educational session on anticoagulation provided by a pharmacist. Patients randomized to the self-management group (58 patients) also received practical training to use the CoaguChek XS device and a self-management dosing algorithm. Patients in the control group (56 patients) continued to undergo standard management at the anticoagulation clinic. Patients completed a validated quality-of-life questionnaire and the validated Oral Anticoagulation Knowledge test at the beginning and end of the study. The quality of anticoagulation control was evaluated by using the time spent in therapeutic range. After 4 months of follow-up, a significant improvement in the self-management group was observed compared with the control group in four of the five quality-of-life topics (p<0.05). Improvements in knowledge were observed in both groups after the training session and persisted after 4 months (p<0.05 for all). The time spent in the therapeutic range (80.0% in the self-management group vs 75% in the control group, p=0.79) and in the extended therapeutic range ([target international normalized ratio ± 0.3] 93.2% in the self-management group vs 91.1% in the control group, p=0.30) were similar between groups. A self-management warfarin program led by pharmacists resulted in significant improvement in the quality of life of patients receiving warfarin therapy as well as a reduction in the time required for anticoagulation monitoring, while maintaining a level of anticoagulation control similar to a high-quality specialized anticoagulation clinic. © 2012 Pharmacotherapy Publications, Inc.

48 CFR 1552.235-71 - Treatment of confidential business information.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Control Act (33 U.S.C. 1251, et seq.), the Safe Drinking Water Act (42 U.S.C. 300f et seq.), the Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 136 et seq.), the Federal Food, Drug, and Cosmetic Act... Toxic Substances Control Act (15 U.S.C. 2601 et seq.). EPA regulations on confidentiality of business...

48 CFR 1552.235-71 - Treatment of confidential business information.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Control Act (33 U.S.C. 1251, et seq.), the Safe Drinking Water Act (42 U.S.C. 300f et seq.), the Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 136 et seq.), the Federal Food, Drug, and Cosmetic Act... Toxic Substances Control Act (15 U.S.C. 2601 et seq.). EPA regulations on confidentiality of business...

48 CFR 1552.235-71 - Treatment of confidential business information.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Control Act (33 U.S.C. 1251, et seq.), the Safe Drinking Water Act (42 U.S.C. 300f et seq.), the Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 136 et seq.), the Federal Food, Drug, and Cosmetic Act... Toxic Substances Control Act (15 U.S.C. 2601 et seq.). EPA regulations on confidentiality of business...

48 CFR 1552.235-71 - Treatment of confidential business information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Control Act (33 U.S.C. 1251, et seq.), the Safe Drinking Water Act (42 U.S.C. 300f et seq.), the Federal Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 136 et seq.), the Federal Food, Drug, and Cosmetic Act... Toxic Substances Control Act (15 U.S.C. 2601 et seq.). EPA regulations on confidentiality of business...

29 CFR 1910.1200 - Hazard communication.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., Fungicide, and Rodenticide Act (7 U.S.C. 136 et seq.), when subject to the labeling requirements of that Act... chemical substance or mixture as such terms are defined in the Toxic Substances Control Act (15 U.S.C. 2601..., and Cosmetic Act (21 U.S.C. 301 et seq.) or the Virus-Serum-Toxin Act of 1913 (21 U.S.C. 151 et seq...

Specific persistence and fate of a soil active herbicide-hexazinone and implications for management

Treesearch

J.L. Michael

2001-01-01

Federal pesticide regulation began officially in 1947 with the promulgation of P.L. 80-104, also known as the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). This early version was administered by the U.S. Department of Agriculture. Responsibility for administration of FIFRA was transferred to the U.S. Environmental Protection Agency (EPA) when it was...

Illinois Pesticide Applicator Study Guide. A Training Manual for Private and Commercial Pesticide Applicators and Operators. Special Publication 39.

ERIC Educational Resources Information Center

Bever, Wayne; And Others

This study guide is designed to provide the necessary information to prepare for certification as a private or commercial pesticide applicator. In addition to providing basic information covering the various sections of the amended Federal Insecticide, Fungicide, and Rodenticide Act, it contains a glossary of common pesticide terms, a list of…

Impact of Anticoagulation in Elderly Patients With Pulmonary Embolism That Undergo IVC Filter Placement: A Retrospective Cohort Study.

PubMed

Falatko, John M; Dalal, Bhavinkumar; Qu, Lihua

2017-12-01

Anticoagulation is the primary treatment for pulmonary embolism (PE). Inferior vena cava (IVC) filters are an adjunctive intervention to prevent recurrent pulmonary embolism. Long-term outcomes in elderly patients with contraindications to anticoagulation after IVC filter placement for prevention of recurrent pulmonary embolism have yet to be assessed. Patients ≥60years of age, that had an IVC filter placed between 1 January, 2008 and 2 February, 2013, with a primary diagnosis of pulmonary embolism, were included. Patients that died during index hospitalisation, were discharged to hospice, or had active malignancy were excluded. The primary endpoint was overall survival. Patients were divided depending on whether they were treated with an approved anticoagulant for VTE or had no anticoagulant. Of the 152 patients identified, 55 were not anti-coagulated after IVC filter placement. The incidence of death was 0.4 per 1000 filter days and 0.7 per 1000 filter days in the anti-coagulated and untreated groups respectively (p-value=0.06). After statistical correction for co-morbid conditions, the effect of anticoagulation was not significant (HR 0.82 CI 0.49-1.37, p-value 0.46). Age was a significant confounder that was associated with death. Increased BMI was protective. Indications for IVC filter placement were numerous, but similar between the two groups. Treatment with an approved anticoagulant is recommended after IVC filter placement for prevention of recurrent PE, however its effect may be attenuated by advanced age. In elderly patients that have undergone IVC filter placement for prevention of recurrent PE, survival may be more dependent on age and co-morbid conditions than exposure to anticoagulation. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Oral anticoagulation management in patients with atrial fibrillation undergoing cardiac implantable electronic device implantation.

PubMed

Black-Maier, Eric; Kim, Sunghee; Steinberg, Benjamin A; Fonarow, Gregg C; Freeman, James V; Kowey, Peter R; Ansell, Jack; Gersh, Bernard J; Mahaffey, Kenneth W; Naccarelli, Gerald; Hylek, Elaine M; Go, Alan S; Peterson, Eric D; Piccini, Jonathan P

2017-09-01

Oral anticoagulation (OAC) therapy is associated with increased periprocedural risks after cardiac implantable electronic device (CIED) implantation. Patterns of anticoagulation management involving non-vitamin K antagonist oral anticoagulants (NOACs) have not been characterized. Anticoagulation strategies and outcomes differ by anticoagulant type in patients undergoing CIED implantation. Using the nationwide Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we assessed how atrial fibrillation (AF) patients undergoing CIED implantation were cared for and their subsequent outcomes. Outcomes were compared by oral anticoagulant therapy (none, warfarin, or NOAC) as well as by anticoagulation interruption status. Among 9129 AF patients, 416 (5%) underwent CIED implantation during a median follow-up of 30 months (interquartile range, 24-36). Of these, 60 (14%) had implantation on a NOAC. Relative to warfarin therapy, those on a NOAC were younger (70.5 years [range, 65-77.5 years] vs 77 years [range, 70-82 years]), had less valvular heart disease (15.0% vs 31.3%), higher creatinine clearance (67.3 [range, 59.7-99.0] vs 65.8 [range, 50.0-91.6]), were more likely to have persistent AF (26.7% vs 22.9%), and use concomitant aspirin (51.7% vs 35.2%). OAC therapy was commonly interrupted for CIED in 64% (n = 183 of 284) of warfarin patients and 65% (n = 39 of 60) of NOAC patients. Many interrupted patients received intravenous bridging anticoagulation: 33/183 (18%) interrupted warfarin and 4/39 (10%) interrupted NOAC patients. Thirty-day periprocedure bleeding and stroke adverse events were infrequent. Management of anticoagulation among AF patients undergoing CIED implantation is highly variable, with OAC being interrupted in more than half of both warfarin- and NOAC-treated patients. Bleeding and stroke events were infrequent in both warfarin and NOAC-treated patients. © 2017 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.

Plasma clot formation and clot lysis to compare effects of different anticoagulation treatments on hemostasis in patients with atrial fibrillation.

PubMed

Königsbrügge, Oliver; Weigel, Günter; Quehenberger, Peter; Pabinger, Ingrid; Ay, Cihan

2018-02-07

The effect of direct oral anticoagulants (DOACs) on turbidimetric measurements of plasma clot formation and susceptibility to fibrinolysis may facilitate a comparison between different classes of anticoagulants in plasma samples. We obtained 424 citrate plasma samples from 226 atrial fibrillation patients on anticoagulation and 24 samples without anticoagulation serving as controls. As comparators, we measured the international normalized ratio (INR) for phenprocoumon samples (N = 166), anti-Xa for low molecular weight heparin (LMWH) samples (N = 42), and DOAC levels with mass spectrometry (dabigatran N = 40, rivaroxaban N = 110, apixaban N = 42). Plasma clot formation and lysis were recorded continuously on a photometer after addition of an activation mix (tissue factor 2 pmol/l and tissue plasminogen activator 333 ng/ml). We used linear regression and ANCOVA for correlation analysis. Clot formation lag phase was prolonged in the presence of anticoagulants in a concentration-dependent manner for DOACs (dabigatran Spearman r = 0.74; rivaroxaban r = 0.78; apixaban r = 0.72, all p < 0.0001), INR dependent for phenprocoumon (r = 0.59, p < 0.0001), anti-Xa level dependent in LMWH samples (r = 0.90, p < 0.0001). Maximum rate of clot formation and peak clot turbidity were reduced in the presence of anticoagulants, but correlated only moderately with the comparator measures of anticoagulation. The clot lysis time was inversely correlated with DOAC concentrations in the presence of recombinant thrombomodulin. A direct ex vivo comparison between the effects of different classes of anticoagulants is possible with turbidimetric measurement of plasma clot formation and lysis. Anticoagulation inhibited clot formation in a plasma concentration manner for DOACs, INR dependent for phenprocoumon, and anti-Xa dependent for LMWH. Susceptibility to fibrinolysis increased with increasing DOAC concentrations.

Effective estimation of correct platelet counts in pseudothrombocytopenia using an alternative anticoagulant based on magnesium salt

PubMed Central

Schuff-Werner, Peter; Steiner, Michael; Fenger, Sebastian; Gross, Hans-Jürgen; Bierlich, Alexa; Dreissiger, Katrin; Mannuß, Steffen; Siegert, Gabriele; Bachem, Maximilian; Kohlschein, Peter

2013-01-01

Pseudothrombocytopenia remains a challenge in the haematological laboratory. The pre-analytical problem that platelets tend to easily aggregate in vitro, giving rise to lower platelet counts, has been known since ethylenediamine-tetra acetic acid EDTA and automated platelet counting procedures were introduced in the haematological laboratory. Different approaches to avoid the time and temperature dependent in vitro aggregation of platelets in the presence of EDTA were tested, but none of them proved optimal for routine purposes. Patients with unexpectedly low platelet counts or flagged for suspected aggregates, were selected and smears were examined for platelet aggregates. In these cases patients were asked to consent to the drawing of an additional sample of blood anti-coagulated with a magnesium additive. Magnesium was used in the beginning of the last century as anticoagulant for microscopic platelet counts. Using this approach, we documented 44 patients with pseudothrombocytopenia. In all cases, platelet counts were markedly higher in samples anti-coagulated with the magnesium containing anticoagulant when compared to EDTA-anticoagulated blood samples. We conclude that in patients with known or suspected pseudothrombocytopenia the magnesium-anticoagulant blood samples may be recommended for platelet counting. PMID:23808903

Therapeutic implications of transesophageal echocardiography after transthoracic echocardiography on acute stroke patients

PubMed Central

de Abreu, Tiago Tribolet; Mateus, Sonia; Carreteiro, Cecilia; Correia, Jose

2008-01-01

Background The role of transesophageal echocardiography (TEE) in the evaluation of acute stroke patients is still ill-defined. We conducted a prospective observational study to find the prevalence of TEE findings that indicate anticoagulation as beneficial, in acute ischemic stroke patients without indication for anticoagulation based on clinical, electrocardiographic and transthoracic echocardiography (TTE) findings. Methods We prospectively studied all patients referred to our laboratory for TTE and TEE. Patients were excluded if the diagnosis was not acute ischemic stroke or if they had an indication for anticoagulation based on clinical, electrocardiographic, or TTE data. Patients with TEE findings that might indicate anticoagulation as beneficial were identified. Results A total of 84 patients with acute ischemic stroke and without indication for anticoagulation based on clinical and electrocardiographic or TTE data were included in the study. Findings indicating anticoagulation as beneficial were found in 32.1%: spontaneous echo contrast (1.2%), complex aortic atheroma (27.4%), thrombus (8.3%), and simultaneous patent foramen ovale and atrial septal aneurysm (2.4%). Conclusions The results of our study show that TEE can have therapy implications in 32.1% of ischemic stroke patients in sinus rhythm and with TTE with no indication for anticoagulation. PMID:18629351

Overview of a pharmacist anticoagulation certificate program.

PubMed

Kirk, Julienne K; Edwards, Rebecca; Brewer, Andrew; Miller, Cathey; Bray, Bryan; Groce, James B

2017-07-01

To describe the design of an ongoing anticoagulation certificate program and annual renewal update for pharmacists. Components of the anticoagulation certificate program include home study, pre- and posttest, live sessions, case discussions with evaluation and presentation, an implementation plan, and survey information (program evaluation and use in practice). Clinical reasoning skills were assessed through case work-up and evaluation prior to live presentation. An annual renewal program requires pharmacists to complete home study and case evaluations. A total of 361 pharmacists completed the anticoagulation certificate program between 2002 and 2015. Most (62%) practiced in ambulatory care and 38% in inpatient care settings (8% in both). In the past four years, 71% were working in or starting anticoagulation clinics in ambulatory and inpatient settings. In their evaluations of the program, an average of 90% of participants agreed or strongly agreed the lecture material was relevant and objectives were met. Pharmacists are able to apply knowledge and skills in management of anticoagulation. This structured practice-based continuing education program was intended to enhance pharmacy practice and has achieved that goal. The certificate program in anticoagulation was relevant to pharmacists who attended the program. Copyright © 2017. Published by Elsevier Inc.

Tailoring of TiO2 films by H2SO4 treatment and UV irradiation to improve anticoagulant ability and endothelial cell compatibility.

PubMed

Liao, Yuzhen; Li, Linhua; Chen, Jiang; Yang, Ping; Zhao, Ansha; Sun, Hong; Huang, Nan

2017-07-01

Surfaces with dual functions that simultaneously exhibit good anticoagulant ability and endothelial cell (EC) compatibility are desirable for blood contact materials. However, these dual functions have rarely been achieved by inorganic materials. In this study, titanium dioxide (TiO 2 ) films were treated by sulphuric acid (H 2 SO 4 ) and ultraviolet (UV) irradiation successively (TiO 2 H 2 SO 4 -UV), resulting in good anticoagulant ability and EC compatibility simultaneously. We found that UV irradiation improved the anticoagulant ability of TiO 2 films significantly while enhancing EC compatibility, though not significantly. The enhanced anticoagulant ability could be related to the oxidation of surface-adsorbed hydrocarbons and increased hydrophilicity. The H 2 SO 4 treatment improved the anticoagulant ability of TiO 2 films slightly, while UV irradiation improved the anticoagulant ability strongly. The enhanced EC compatibility could be related to the increased surface roughness and positive charges on the surface of the TiO 2 films. Furthermore, the time-dependent degradation of the enhanced EC compatibility and anticoagulant ability of TiO 2 H 2 SO 4 -UV was observed. In summary, TiO 2 H 2 SO 4 -UV expressed both excellent anticoagulant ability and good EC compatibility at the same time, which could be desirable for blood contact materials. However, the compatibility of TiO 2 H 2 SO 4 -UV with smooth muscle cells (SMCs) and macrophages was also improved. More effort is still needed to selectively improve EC compatibility on TiO 2 films for better re-endothelialization. Copyright © 2017 Elsevier B.V. All rights reserved.

Hospital variability in use of anticoagulant strategies during acute myocardial infarction treated with an early invasive strategy.

PubMed

Arnold, Suzanne V; Li, Shu-Xia; Alexander, Karen P; Spertus, John A; Nallamothu, Brahmajee K; Curtis, Jeptha P; Kosiborod, Mikhail; Gupta, Aakriti; Wang, Tracy Y; Lin, Haiqun; Dharmarajan, Kumar; Strait, Kelly M; Lowe, Timothy J; Krumholz, Harlan M

2015-06-15

During a myocardial infarction, no single best approach of systemic anticoagulation is recommended, likely due to a lack of comparative effectiveness studies and trade-offs between treatments. We investigated the patterns of use and site-level variability in anticoagulant strategies (unfractionated heparin [UFH] only, low-molecular-weight heparin [LMWH] only, UFH+LMWH, any bivalirudin) of 63 796 patients with a principal diagnosis of myocardial infarction treated with an early invasive strategy with percutaneous coronary intervention at 257 hospitals. About half (47%) of patients received UFH only, 6% UFH+LMWH, 7% LMWH only, and 40% bivalirudin. Compared with UFH, the median odds ratio was 2.90 for LMWH+UFH, 4.70 for LMWH only, and 3.09 for bivalirudin, indicating that 2 "identical" patients would have a 3- to 4-fold greater likelihood of being treated with anticoagulants other than UFH at one hospital compared with another. We then categorized hospitals as low- or high-users of LMWH and bivalirudin. Using hierarchical, multivariate regression models, we found that low bivalirudin-using hospitals had higher unadjusted bleeding rates, but the risk-adjusted and anticoagulant-adjusted bleeding rates did not differ across the hospital anticoagulation phenotypes. Risk-standardized mortality and risk-standardized length of stay also did not differ across hospital phenotypes. We found substantial site-level variability in the choice of anticoagulants for invasively managed acute myocardial infarction patients, even after accounting for patient factors. No single hospital-use pattern was found to be clinically superior. More studies are needed to determine which patients would derive the greatest benefit from various anticoagulants and to support consistent treatment of patients with the optimal anticoagulant strategy. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection.

PubMed

Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P; Ismail, Farooq; Im, Sun

2016-04-01

To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. International normalized ratio <2.0 was perceived as an ideal range for performing Botulinum toxin injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%-30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients.

Evaluation of US prescription patterns: Are treatment guidelines for cancer-associated venous thromboembolism being followed?

PubMed

Khorana, Alok A; Yannicelli, Daniel; McCrae, Keith R; Milentijevic, Dejan; Crivera, Concetta; Nelson, Winnie W; Schein, Jeffrey R

2016-09-01

Venous thromboembolism (VTE) is a common complication of cancer. Clinical practice guidelines recommend low-molecular-weight heparin (LMWH) for treatment of cancer-associated VTE, but it is unclear how frequently these are followed. This study assessed anticoagulation treatment patterns for VTE in newly diagnosed cancer patients in the United States. MarketScan® claims records of more than 80 million insured members between January 1, 2009 and July 31, 2014 were retrospectively analyzed. Subjects were included if they were 18years of age or older, and had a diagnosis of cancer (9 solid tumor types) and VTE. Data were included for LMWH, warfarin, and other anticoagulants (fondaparinux and direct oral anticoagulants [DOACs]). Patients with anticoagulant treatment prior to cancer diagnosis were excluded. VTE developed in 6.2% of cancer patients (median, 181days after cancer diagnosis). VTE rates were highest for pancreatic (17.5%) and lung (12.6%) cancer and lowest for breast (4.2%) and prostate (4.1%) cancer. For patients for whom outpatient prescription data were available, warfarin was most commonly used (50.0%), followed by LMWH (40.0%) and other anticoagulants (10.0%). Over 6months, 13% of patients who initiated injectable anticoagulants remained on them compared with 30% of those who initiated oral anticoagulants. More patients switched from LMWH to warfarin and other anticoagulants (44%) versus those who switched from warfarin (28%). Warfarin was the most utilized anticoagulant for cancer-associated VTE despite guideline recommendations for LMWH. More patients remained on oral versus injectable agents, which may be related to self-injection burden and costs. Copyright © 2016 Elsevier Ltd. All rights reserved.

The incidence of traumatic intracranial hemorrhage in head-injured older adults transported by EMS with and without anticoagulant or antiplatelet use.

PubMed

Nishijima, Daniel Kiden; Gaona, Samuel D; Waechter, Trent; Maloney, Ric; Blitz, Adam; Elms, Andrew R; Farrales, Roel D; Montoya, James; Bair, Troy; Howard, Calvin; Gilbert, Megan; Trajano, Renee; Hatchel, Kaela; Faul, Mark; Bell, Jeneita M; Coronado, Victor; Vinson, David R; Ballard, Dustin W; Tancredi, Daniel J; Garzon, Hernando; Mackey, Kevin E; Shahlaie, Kiarash; Holmes, James F

2017-11-06

Field triage guidelines recommend transport of head-injured patients on anticoagulants or antiplatelets to a higher-level trauma center based on studies suggesting a high incidence of traumatic intracranial hemorrhage (tICH). We compared the incidence of tICH in older adults transported by EMS with and without anticoagulation or antiplatelet use and evaluated the accuracies of different sets of field triage criteria to identify tICH. This was a prospective, observational study at 5 EMS agencies and 11 hospitals. Older adults (≥55 years) with head trauma and transported by EMS from Aug 2015 to Sept 2016 were eligible. EMS providers completed standardized data forms and patients were followed through ED or hospital discharge. We enrolled 1,304 patients; 1147 (88%) received a cranial CT scan and were eligible for analysis. 434 (33%) patients had anticoagulant or antiplatelet use and 112 (10%) had tICH. The incidence of tICH in patients with (11%, 95%CI 8-14%) and without (9%, 95%CI 7-11%) anticoagulant or antiplatelet use was similar. Anticoagulant or antiplatelet use was not predictive of tICH on adjusted analysis. Steps 1-3 criteria alone were not sensitive in identifying tICH (27%) while the addition of anticoagulant or antiplatelet criterion improved sensitivity (63%). Other derived sets of triage criteria were highly sensitive (>98%) but poorly specific (<11%). The incidence of tICH was similar between patients with and without anticoagulant or antiplatelet use. Use of anticoagulant or antiplatelet medications was not a risk factor for tICH. We were unable to identify a set of triage criteria that was accurate for trauma center need.

Switching, Adverse Effects and Use of Over-the-Counter Analgesics among Users of Oral Anticoagulants: A Pharmacy-based Survey.

PubMed

Hellfritzsch, Maja; Hyllested, Lea Maria Rønneberg; Meegaard, Line; Wiberg-Hansen, Alexander; Grove, Erik Lerkevang; Pottegård, Anton

2017-07-01

Oral anticoagulants are widely used but information on important aspects in that respect is not available from medical registers or clinical databases. Therefore, we conducted a survey including patients filling a prescription for oral anticoagulants at two large Danish community pharmacies. We collected information concerning the patients' knowledge of their anticoagulant treatment including prior drug switching. Further, patients were asked about use of over-the-counter analgesics, adverse effects and how the treatment affected their everyday life. Among 335 eligible patients, 301 (90%) agreed to participate. Atrial fibrillation was the most common indication (65%), and most patients filled a prescription for a non-vitamin K antagonist oral anticoagulant (NOAC) (58%). Among the 12% (n = 35) of participants who had switched oral anticoagulant treatment, 69% had switched from a vitamin K antagonist (VKA) to a NOAC. Switching was most frequently caused by inconvenience (34%) and adverse effects (23%). Although half of all patients had recently bought over-the-counter analgesics, purchase of ibuprofen and aspirin was rare (6%). More VKA users than NOAC users felt limited in their everyday life because of anticoagulant treatment (18% versus 9%). Among non-incident NOAC users, 21% had experienced adverse effects during their current treatment. Based on first-hand information from a large sample of anticoagulant users, we conclude that the main drug-related issues leading to anticoagulant switching and perceived limitations in everyday life were inconvenience and adverse effects. This varied between drug groups. Further, use of NSAIDs obtained over the counter was rare. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Four Thrombotic Events Over 5 Years, Two Pulmonary Emboli and Two Deep Venous Thrombosis, When Testosterone-HCG Therapy Was Continued Despite Concurrent Anticoagulation in a 55-Year-Old Man With Lupus Anticoagulant.

PubMed

Glueck, Charles J; Lee, Kevin; Prince, Marloe; Jetty, Vybhav; Shah, Parth; Wang, Ping

2016-01-01

When exogenous testosterone or treatments to elevate testosterone (human chorionic gonadotropin [HCG] or Clomid) are prescribed for men who have antecedent thrombophilia, deep venous thrombosis and pulmonary embolism often occur and may recur despite adequate anticoagulation if testosterone therapy is continued. A 55-year-old white male was referred to us because of 4 thrombotic events, 3 despite adequate anticoagulation over a 5-year period. We assessed interactions between thrombophilia, exogenous testosterone therapy, and recurrent thrombosis. In 2009, despite low-normal serum testosterone 334 ng/dL (lower normal limit [LNL] 300 ng/dL), he was given testosterone (TT) cypionate (50 mg/week) and human chorionic gonadotropin (HCG; 500 units/week) for presumed hypogonadism. Ten months later, with supranormal serum T (1385 ng/dL, upper normal limit [UNL] 827 ng/dL) and estradiol (E2) 45 pg/mL (UNL 41 pg/mL), he had a pulmonary embolus (PE) and was then anticoagulated for 2 years (enoxaparin, then warfarin). Four years later, on TT-HCG, he had his first deep venous thrombosis (DVT). TT was stopped and HCG continued; he was anticoagulated (enoxaparin, then warfarin, then apixaban, then fondaparinux). One year after his first DVT, on HCG, still on fondaparinux, he had a second DVT (5/315), was anticoagulated (enoxaparin + warfarin), with a Greenfield filter placed, but 8 days later had a second PE. Thrombophilia testing revealed the lupus anticoagulant. After stopping HCG, and maintained on warfarin, he has been free of further DVT-PE for 9 months. When DVT-PE occur on TT or HCG, in the presence of thrombophilia, TT-HCG should be stopped, lest DVT-PE reoccur despite concurrent anticoagulation.

Variations in Anticoagulation Practices Following the Maze Procedure.

PubMed

Chung, Jennifer; Sami, Magdi; Albert, Carole; Varennes, Benoit De

2015-01-01

The current real-world anticoagulation practices following left atrial appendectomy in the context of the Maze procedure are unknown. This is a cohort study of all patients who underwent the Maze procedure with amputation of the left atrial appendage from June 2005 to November 2012. Data was prospectively collected at regular intervals with an interview and Holter monitoring. All patients received anticoagulation for 3 months. Those then kept on anticoagulation and those for whom anticoagulation was stopped were compared in terms of death, bleeding and incidence of stroke. In total, there were 113 patients, of whom 66 were treated with anticoagulation (Group A) and 47 were not (Group B). There were no significant baseline differences between the two groups, including the presence of atrial fibrillation (A:19.7%, B:10.6%, p=0.30), CHADS2 score (A:1.41±1.05, B:1.15±1.08, p=0.19), and left atrial size (A:48.3±7.1mm, B:47.6±7.8 mm, p=0.57). There were 275 patient-years of follow-up, with an average of 2.43 years per patient. Only two patients experienced strokes, both in Group A (p=0.27). Of the 5 bleeding events, 4 occurred in the first 3 months while on anticoagulation and the remaining event occurred in Group A at 3 years post-operatively (p=0.10). No standardized approach to anticoagulation after the Maze procedure is apparent in real-world practice in an urban Canadian setting. Patients who undergo the Maze procedure with amputation of the left atrial appendage are at a low risk of stroke, but the optimal anticoagulation strategy requires further investigation.

[The current role of warfarin].

PubMed

Michalcová, Jana; Buliková, Alena; Zavřelová, Jiřina; Prudková, Marie; Penka, Miroslav

Well-managed warfarin therapy remains an important method of anticoagulation in the 21st century, despite the introduction of new antithrombotics into the clinical practice. The main advantages of warfarin are decades of treatment experience, the possibility to monitor its anticoagulant effect using the INR and the last, but not least, the low cost. Currently, approximately 75 % of anticoagulated patients in the Czech Republic are treated with warfarin and warfarin remains the only option for oral anticoagulant therapy in certain clinical conditions (particularly in patients with valvular atrial fibrillation or mechanical heart valves). For physicians across specialties it is still indispensable to master the basics of safe and effective warfarin therapy, including the management of treatment complications.Key words: anticoagulant therapy - INR - thrombosis - warfarin.

Isolation and characterization of an anticoagulant present in the salivary glands of the bont-legged tick, Hyalomma truncatum.

PubMed

Joubert, A M; Crause, J C; Gaspar, A R; Clarke, F C; Spickett, A M; Neitz, A W

1995-02-01

A low molecular mass anticoagulant (17 kDa) was isolated from the salivary glands of prefed female Hyalomma truncatum ticks by means of reverse phase and anion-exchange HPLC. Trypsin digestion and amino acid analysis confirmed the protein nature of the anticoagulant. The inhibitor appears to be uncompetitive with a Ki of 6.9 x 10(-10)M. The target of the anticoagulant is factor Xa at the junction of the extrinsic and intrinsic pathways. This may be crucial for the survival of the tick, making it feasible to investigate the possibility of vaccination with this antihaemostatic against tick feeding. In addition, tick anticoagulants may possibly have therapeutic application in controlling thrombosis.

Anticoagulation management in the ambulatory surgical setting.

PubMed

Eisenstein, Diana Hill

2012-04-01

Many people receiving maintenance anticoagulation therapy require surgery each year in ambulatory surgery centers. National safety organizations focus attention toward improving anticoagulation management, and the American College of Chest Physicians has established guidelines for appropriate anticoagulation management to balance the risk of thromboembolism when warfarin is discontinued with the risk of bleeding when anticoagulation therapy is maintained. The guidelines recommend that patients at high or moderate risk for thromboembolism should be bridged with subcutaneous low-molecular-weight heparin or IV unfractionated heparin with the interruption of warfarin, and low-risk patients may require subcutaneous low-molecular-weight heparin or no bridging with the interruption of warfarin. The guidelines recommend the continuation of warfarin for patients who are undergoing minor dermatologic or dental procedures or cataract removal. The literature reveals, however, that there is not adequate adherence to these recommendations and guidelines. Management of anticoagulation therapy by a nurse practitioner may improve compliance and safety in ambulatory surgery centers. Copyright © 2012 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Outpatient management of oral vitamin K antagonist therapy: defining and measuring high-quality management.

PubMed

Phillips, Katherine W; Ansell, Jack

2008-01-01

Oral anticoagulation therapy with warfarin is the mainstay of prevention and treatment of thromboembolic disease. However, it remains one of the leading causes of harmful medication errors and medication-related adverse events. The beneficial outcomes of oral anticoagulation therapy are directly dependent upon the quality of dose and anticoagulation management, but the literature is not robust with regards to what constitutes such management. This review focuses on, and attempts to define, the parameters of high-quality anticoagulation management and identifies the appropriate outcome measures constituting high-quality management. Elements discussed include the most fundamental measure, time in therapeutic range, along with other parameters including therapy initiation, time to therapeutic range, dosing management when patients are not in therapeutic range, perioperative dosing management, patient education, and other important outcome measures. Healthcare providers who manage oral anticoagulation therapy should utilize these parameters as a measure of their performance in an effort to achieve high-quality anticoagulation management.

[The study of anticoagulants selection in platelet-rich plasma preparation].

PubMed

Hua, Lei; Lai, Gui; Zhenjun, Liu; Guie, Ma

2015-07-01

To investigate the effect of the anticoagulants on PRP quality, so as to clarify the appropriate anticoagulant used in PRP production. The microstructure change of platelets collected via heparin, citrate, acid citrate dextrose (ACD) and citrate-theophylline-adenosine-dipyridamole ( CTAD) was observed by TEM following time course. The extent of spontaneous activation of platelets in four groups was detected by measuring sP-selectin in plasma. The TGF-β1 release amount of activated PRP of four groups was measured. CTAD is superior to other anticoagulants in maintaining the integrity of platelet structures for a long time and preventing platelet spontaneous activation. ACD slightly surpassed heparin and citrate in above two aspects. ACD-PRP and CTAD-PRP released significantly more TGF-β1 compared with heparin and citrate. The PRP quality and biological effects were strongly associated with the type of Anticoagulants. ACD and CTAD are optimal anticoagulants in PRP production for they can maintain platelet viability at a high level.

Assessing Bleeding Risk in Patients Taking Anticoagulants

PubMed Central

Shoeb, Marwa; Fang, Margaret C.

2013-01-01

Anticoagulant medications are commonly used for the prevention and treatment of thromboembolism. Although highly effective, they are also associated with significant bleeding risks. Numerous individual clinical factors have been linked to an increased risk of hemorrhage, including older age, anemia, and renal disease. To help quantify hemorrhage risk for individual patients, a number of clinical risk prediction tools have been developed. These risk prediction tools differ in how they were derived and how they identify and weight individual risk factors. At present, their ability to effective predict anticoagulant-associated hemorrhage remains modest. Use of risk prediction tools to estimate bleeding in clinical practice is most influential when applied to patients at the lower spectrum of thromboembolic risk, when the risk of hemorrhage will more strongly affect clinical decisions about anticoagulation. Using risk tools may also help counsel and inform patients about their potential risk for hemorrhage while on anticoagulants, and can identify patients who might benefit from more careful management of anticoagulation. PMID:23479259

Oral Anticoagulant Therapy

PubMed Central

Gallus, Alexander S.; Wittkowsky, Ann; Crowther, Mark; Hylek, Elaine M.; Palareti, Gualtiero

2012-01-01

Background: The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management. Methods: We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban Results: The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal. Conclusions: There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban. PMID:22315269

Effect of post-filter anticoagulation on mortality in patients with cancer-associated pulmonary embolism.

PubMed

Kang, Jieun; Kim, Seon Ok; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Jae Seung

2018-05-17

Malignancy is associated with an increased risk of venous thromboembolism. Inferior vena cava filters are a viable alternative when anticoagulation is infeasible because of the risk of bleeding. Although the current guidelines recommend that all patients with a vena cava filter be treated with anticoagulation treatment when the risk of bleeding is reduced, studies concerning the role of concomitant anticoagulation after vena cava filter insertion in high-risk patients are scarce. Since many cancer patients suffer from a high risk of hemorrhagic complications, we aimed to determine the effect of post-filter anticoagulation on mortality in patients with a malignant solid tumor. A retrospective cohort study of patients with pulmonary embolism was performed between January 2010 and May 2016. Patients with a solid tumor and vena cava filter inserted because of pulmonary embolism were included. Using Cox proportional hazards model, the prognostic effect of clinical variables was analyzed. A total of 180 patients were analyzed, with 143 patients receiving and 37 patients not receiving post-filter anticoagulation treatment. Mortality was not significantly different between the two groups. The presence of metastatic cancer and that of pancreatobiliary cancer were significant risk factors for mortality. However, post-filter anticoagulation did not show significant effect on mortality regardless of the stage of cancer. In patients with cancer-associated pulmonary embolism, the effect of post-filter anticoagulation on mortality may not be critical, especially in patients with a short life expectancy.

Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs direct oral anticoagulants.

PubMed

Yanagisawa, Naohiro; Nagata, Naoyoshi; Watanabe, Kazuhiro; Iida, Tatsuhiro; Hamada, Mariko; Kobayashi, Sakurako; Shimbo, Takuro; Akiyama, Junichi; Uemura, Naomi

2018-04-14

To verify the validity of the endoscopy guidelines for patients taking warfarin or direct oral anticoagulants (DOAC). We collected data from 218 patients receiving oral anticoagulants (73 DOAC users, 145 warfarin users) and 218 patients not receiving any antithrombotics (age- and sex-matched controls) who underwent polypectomy. (1) We evaluated post-polypectomy bleeding (PPB) risk in patients receiving warfarin or DOAC compared with controls; (2) we assessed the risks of PPB and thromboembolism between three AC management methods: Discontinuing AC with heparin bridge (HPB) (endoscopy guideline recommendation), continuing AC, and discontinuing AC without HPB. PPB rate was significantly higher in warfarin users and DOAC users compared with controls (13.7% and 13.7% vs 0.9%, P < 0.001), but was not significantly different between rivaroxaban (13.2%), dabigatran (11.1%), and apixaban (13.3%) users. Two thromboembolic events occurred in warfarin users, but none in DOAC users. Compared with the continuing anticoagulant group, the discontinuing anticoagulant with HPB group (guideline recommendation) had a higher PPB rate (10.8% vs 19.6%, P = 0.087). These findings were significantly evident in warfarin but not DOAC users. One thrombotic event occurred in the discontinuing anticoagulant with HPB group and the discontinuing anticoagulant without HPB group; none occurred in the continuing anticoagulant group. PPB risk was similar between patients taking warfarin and DOAC. Thromboembolism was observed in warfarin users only. The guideline recommendations for HPB should be re-considered.

Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies.

PubMed

Suleria, Hafiz Ansar Rasul; Masci, Paul P; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A; Gobe, Glenda C

2017-08-04

Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic.

Dietary vitamin K guidance: an effective strategy for stable control of oral anticoagulation?

USDA-ARS?s Scientific Manuscript database

Numerous factors have been identified as risk factors for instability of oral anticoagulation, including variability in vitamin K intake. However few studies have directly tested the feasibility of manipulating dietary vitamin K to achieve stable oral anticoagulation. Recent findings from a rando...

Anticoagulation Quality Assessment in Patients with Nonvalvular Atrial Fibrillation (NVAF) and Comparison with Major Trials of Direct-Acting Oral Anticoagulants

DTIC Science & Technology

2016-04-22

Purpose: The benefits of warfarin anticoagulation therapy are strongly correlated with the ability to maintain patients’ INR goal, known as the time...Rosendaal). Differences in TTR calculations could alter perceptions about the effectiveness of warfarin therapy.

Scintigraphic detection of occult hemorrhage in a patient receiving anticoagulants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenbaum, R.C.; Johnston, G.S.; Whitley, N.O.

1986-02-01

The exact location of hemorrhage complicating anticoagulant therapy is sometimes difficult to establish. We present a case in which imaging with 99mTc-labeled red cells had a significant role in the diagnosis of soft-tissue bleeding in a paraplegic patient receiving long-term anticoagulation.

Breast hematoma complicating anticoagulant therapy: management and literature review.

PubMed

Salemis, Nikolaos S

2012-01-01

Anticoagulant-induced spontaneous breast hematoma is a very rare clinical entity with only a few cases reported in the literature so far. We describe a case of a spontaneous breast hematoma in a female patient under combined oral anticoagulant and antiplatelet therapy. Physicians should be aware of this possibility in patients under anticoagulant treatment presenting with sudden onset of breast pain and a palpable mass. Repeat imaging is mandatory until complete clinical and imaging resolution of the hematoma. If an abnormality persists, further investigation is needed to exclude an underlying malignancy.

Stroke prevention in the elderly atrial fibrillation patient with comorbid conditions: focus on non-vitamin K antagonist oral anticoagulants

PubMed Central

Turagam, Mohit K; Velagapudi, Poonam; Flaker, Greg C

2015-01-01

Stroke prevention in elderly atrial fibrillation patients remains a challenge. There is a high risk of stroke and systemic thromboembolism but also a high risk of bleeding if anticoagulants are prescribed. The elderly have increased chronic kidney disease, coronary artery disease, polypharmacy, and overall frailty. For all these reasons, anticoagulant use is underutilized in the elderly. In this manuscript, the benefits of non-vitamin K antagonist oral anticoagulants compared with warfarin in the elderly patient population with multiple comorbid conditions are reviewed. PMID:26366064

Anticoagulant therapy: basic principles, classic approaches and recent developments.

PubMed

Sinauridze, Elena I; Panteleev, Mikhail A; Ataullakhanov, Fazoil I

2012-09-01

The standard multipotent anticoagulants (unfractionated and low molecular weight heparins, antagonists of vitamin K) are commonly used for treatment and/or prophylaxis of different thrombotic complications, such as deep vein thrombosis, thrombophilia, pulmonary embolism, myocardial infarction, stroke and so on. Advantages and shortcomings of these anticoagulants are considered. The modern tendencies to use small selective direct inhibitors of thrombin or factor Xa are surveyed. The search of the new targets in the coagulation cascade for development of new promising anticoagulants and improvement in antithrombotic therapy is discussed.

Economic evaluation of prescribing conventional and newer oral anticoagulants in older adults.

PubMed

Hasan, Syed Shahzad; Kow, Chia Siang; Curley, Louise E; Baines, Darrin L; Babar, Zaheer-Ud-Din

2018-05-09

Anticoagulants refer to a variety of agents that inhibit one or more steps in the coagulation cascade. Generally, clinical conditions that require the prescribing of an oral anticoagulant increase in frequency with age. However, a major challenge of anticoagulation use among older patients is that this group of patients also experience the highest bleeding risk. To date, economic evaluation of prescribing of anticoagulants that includes the novel or newer oral anticoagulants (NOACs) in older adults has not been conducted and is warranted. Areas covered: A review of articles that evaluated the cost of prescribing conventional (e.g. vitamin K antagonists) and NOACs (e.g. direct thrombin inhibitors and direct factor Xa inhibitors) in older adults. Expert commentary: While the use of NOACs significantly increases the cost of the initial treatment for thromboembolic disorders, they are still considered cost-effective relative to warfarin since they offer reduced risk of intracranial haemorrhagic events. The optimum anticoagulation with warfarin can be achieved by providing specialised care; clinics managed by pharmacists have been shown to be cost-effective relative to usual care. There are suggestions that genotyping the CYP2C9 and VKORC1 genes is useful for determining a more appropriate initial dose and thereby increasing the effectiveness and safety of warfarin.

Stroke prophylaxis with warfarin or dabigatran for patients with non-valvular atrial fibrillation-cost analysis.

PubMed

Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

2012-09-01

cost of anticoagulation with dabigatran is largely based on estimation of complication rates derived from clinical trials. to investigate cost of anticoagulation with dabigatran in comparison with warfarin in clinical practice. a prospective observational study of patients with non-vavular atrial fibrillation (NVAF) referred to anticoagulation clinic. Patients were interviewed (4-6 weekly by telephone) about bleeding events. Costs of anticoagulation were calculated as: (i) drug cost, (ii) international normalised ratio (INR) monitoring cost and (iii) bleeding cost. For cost calculation of dabigatran, INR monitoring cost was omitted. a total of 402 patients were included and followed up for a mean (SD) of 19 (8.1) months. Annual cost of anticoagulation was £207.3 and £1,573.5 per patient for warfarin and dabigatran, respectively. Drug price constituted 13.6% of the total cost for warfarin and 94% for dabigatran. Total cost of anticoagulation to prevent one stroke per year was £6,219, £28,086.5 and £25,181 for warfarin, dabigatran 110 and 150 mg, respectively. cost of anticoagulation is mainly driven by drug price for dabigatran and quality of INR control for warfarin. Until the price of dabigatran is reviewed, warfarin remains suitable for the majority of patients with NVAF.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study.

PubMed

Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Caso, Valeria; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H; Michel, Patrik; Cordier, Maria; Vanacker, Peter; Remillard, Suzette; Alberti, Andrea; Venti, Michele; Scoditti, Umberto; Denti, Licia; Orlandi, Giovanni; Chiti, Alberto; Gialdini, Gino; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Putaala, Jukka; Tatlisumak, Turgut; Masotti, Luca; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Martini, Giuseppe; Tsivgoulis, Georgios; Vadikolias, Kostantinos; Liantinioti, Chrissoula; Corea, Francesco; Del Sette, Massimo; Ageno, Walter; De Lodovici, Maria Luisa; Bono, Giorgio; Baldi, Antonio; D'Anna, Sebastiano; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Acciarresi, Monica; D'Amore, Cataldo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Consoli, Domenico; Galati, Franco; Pieroni, Alessio; Toni, Danilo; Monaco, Serena; Baronello, Mario Maimone; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Mosconi, Maria Giulia; Bubba, Valentina; Silvestri, Ilenia; Lees, Kennedy R

2015-08-01

The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants. © 2015 American Heart Association, Inc.

Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis.

PubMed

van Walraven, Carl; Hart, Robert G; Singer, Daniel E; Laupacis, Andreas; Connolly, Stuart; Petersen, Palle; Koudstaal, Peter J; Chang, Yuchiao; Hellemons, Beppie

2002-11-20

Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke and other vascular events. To compare the risk of vascular and bleeding events in patients with nonvalvular AF treated with vitamin K -inhibiting oral anticoagulants or acetylsalicylic acid (aspirin). Pooled analysis of patient-level data from 6 published, randomized clinical trials. A total of 4052 patients with AF randomly assigned to receive therapeutic doses of oral anticoagulant or aspirin with or without low-dose oral anticoagulants. Ischemic and hemorrhagic stroke, other cardiovascular events, all-cause death, and major bleeding events. Person-year incidence rates were calculated to provide crude comparisons. Relative efficacy was assessed using proportional hazards modeling stratified by study. The variation of the oral anticoagulant's relative effect by pertinent patient factors was explored with interaction terms. All analyses were conducted using the intention-to-treat principle. Patients receiving oral anticoagulant and aspirin were balanced for important prognostic factors. There was no significant heterogeneity between trials in the relative efficacy of oral anticoagulant vs aspirin for any outcome. Patients receiving oral anticoagulant were significantly less likely to experience any stroke (2.4 vs 4.5 events per 100 patient-years; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.43-0.71), ischemic stroke (HR, 0.48; 95% CI, 0.37-0.63), or cardiovascular events (HR, 0.71; 95% CI, 0.59-0.85) but were more likely to experience major bleeding (2.2 vs 1.3 events per 100 patient-years; HR, 1.71; 95% CI, 1.21-2.41). The reduction in ischemic stroke risk was similar in patients with paroxysmal AF (1.5 vs 4.7 events per 100 patient-years; HR, 0.32; 95% CI, 0.16-0.61; P<.001). Treating 1000 patients with AF for 1 year with oral anticoagulant rather than aspirin would prevent 23 ischemic strokes while causing 9 additional major bleeds. Overall all-cause survival did not differ but appeared to improve for oral anticoagulant patients 3 years after therapy was started. Compared with aspirin, oral anticoagulant significantly decreases the risk of all strokes, ischemic strokes, and cardiovascular events for patients with nonvalvular chronic or paroxysmal AF but modestly increases the absolute risk of major bleeding. The balance of benefits and risks varies by patient subgroup.

Effect of anticoagulants on the protein corona-induced reduced drug carrier adhesion efficiency in human blood flow.

PubMed

Sobczynski, Daniel J; Eniola-Adefeso, Omolola

2017-01-15

Plasma proteins rapidly coat the surfaces of particulate drug carriers to form a protein corona upon their injection into the bloodstream. The high presence of immunoglobulins in the corona formed on poly(lactic-co-glycolic acid) (PLGA) vascular-targeted carrier (VTC) surfaces was recently shown to negatively impact their adhesion to activated endothelial cells (aECs) in vitro. Here, we characterized the influence of anticoagulants, or their absence, on the binding efficiency of VTCs of various materials via modulation of their protein corona. Specifically, we evaluated the adhesion of PLGA, poly(lactic acid) (PLA), polycaprolactone (PCL), silica, and polystyrene VTCs to aECs in heparinized, citrated, and non-anticoagulated (serum and whole) blood flows relative to buffer control. Particle adhesion is substantially reduced in non-anticoagulated blood flows regardless of the material type while only moderate to minimal reduction is observed for VTCs in anticoagulant-containing blood flow depending on the anticoagulant and material type. The substantial reduction in VTC adhesion in blood flows was linked to a high presence of immunoglobulin-sized proteins in the VTC corona via SDS-PAGE analysis. Of all the materials evaluated, PLGA was the most sensitive to plasma protein effects while PCL was the most resistant, suggesting particle hydrophobicity is a critical component of the observed negative plasma protein effects. Overall, this work demonstrates that anticoagulant positively alters the effect of plasma proteins in prescribing VTC adhesion to aECs in human blood flow, which has implication in the use of in vitro blood flow assays for functional evaluation of VTCs for in vivo use. This study addresses the impact of anticoagulant on altering the extent of the previously observed protein corona-induced adhesion reduction of vascular-targeted drug carriers in human blood flows. Specifically, serum blood flow (no anticoagulant) magnifies the negative effect of the plasma protein corona on drug carrier adhesion relative to citrated or heparinized blood flows. Overall, the results from this work suggest that serum better predicts targeted drug carrier adhesion efficiency in vivo compared to anticoagulant containing plasma. Furthermore, this study offers critical insight into the importance of how the choice of anticoagulant can greatly affect drug delivery-related processes in vitro. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Federal-State Environmental Programs: The State Perspective. A Compilation of Questionnaire Responses. Supplement to a Report to the Congress by the Comptroller General of the United States.

ERIC Educational Resources Information Center

Comptroller General of the U.S., Washington, DC.

Summarized are responses to questionnaires prepared by the United States General Accounting Office (GAO) and mailed to state-level environmental agency administrators. Also included in this survey are state program directors responsible for administering the Clean Air Act; the Federal Insecticide, Fungicide and Rodenticide Act; the Clean Water…

Restarting Anticoagulant Treatment After Intracranial Hemorrhage in Patients With Atrial Fibrillation and the Impact on Recurrent Stroke, Mortality, and Bleeding: A Nationwide Cohort Study.

PubMed

Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Gorst-Rasmussen, Anders; Rasmussen, Lars Hvilsted; Lip, Gregory Y H

2015-08-11

Intracranial hemorrhage is the most feared complication of oral anticoagulant treatment. The optimal treatment option for patients with atrial fibrillation who survive an intracranial hemorrhage remains unknown. We hypothesized that restarting oral anticoagulant treatment was associated with a lower risk of stroke and mortality in comparison with not restarting. Linkage of 3 Danish nationwide registries in the period between 1997 and 2013 identified patients with atrial fibrillation on oral anticoagulant treatment with incident intracranial hemorrhage. Patients were stratified by treatment regimens (no treatment, oral anticoagulant treatment, or antiplatelet therapy) after the intracranial hemorrhage. Event rates were assessed 6 weeks after hospital discharge and compared with Cox proportional hazard models. In 1752 patients (1 year of follow-up), the rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for patients treated with oral anticoagulants was 13.6, in comparison with 27.3 for nontreated patients and 25.7 for patients receiving antiplatelet therapy. The rate of ischemic stroke/systemic embolism and all-cause mortality (per 100 person-years) for recurrent intracranial hemorrhage, the rate of ischemic stroke/systemic embolism, and all-cause mortality (per 100 person-years) patients treated with oral anticoagulants was 8.0, in comparison with 8.6 for nontreated patients and 5.3 for patients receiving antiplatelet therapy. The adjusted hazard ratio of ischemic stroke/systemic embolism and all-cause mortality was 0.55 (95% confidence interval, 0.39-0.78) in patients on oral anticoagulant treatment in comparison with no treatment. For ischemic stroke/systemic embolism and for all-cause mortality, hazard ratios were 0.59 (95% confidence interval, 0.33-1.03) and 0.55 (95% confidence interval, 0.37-0.82), respectively. Oral anticoagulant treatment was associated with a significant reduction in ischemic stroke/all-cause mortality rates, supporting oral anticoagulant treatment reintroduction after intracranial hemorrhage as feasible. Future trials are encouraged to guide clinical practice in these patients. © 2015 American Heart Association, Inc.

Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin.

PubMed

Davidson, Bruce L; Verheijen, Sara; Lensing, Anthonie W A; Gebel, Martin; Brighton, Timothy A; Lyons, Roger M; Rehm, Jeffrey; Prins, Martin H

2014-06-01

Combined anticoagulant and aspirin therapy is associated with increased bleeding risk in patients with atrial fibrillation, but the bleeding risk of combined use of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs) is poorly documented. To estimate the bleeding risk of combined anticoagulant (rivaroxaban or enoxaparin-vitamin K antagonist [VKA]) and NSAID or aspirin therapy in patients with venous thromboembolism. Prospective analysis of observational data from the EINSTEIN deep vein thrombosis and pulmonary embolism clinical trials comparing rivaroxaban with enoxaparin-VKA treatment, trials performed in hospitals and clinics in 8246 patients enrolled from 2007 to 2009. Bleeding event rates during exposure to NSAID and aspirin therapy were compared to time without exposure. Days of NSAID or aspirin use and nonuse, clinically relevant bleeding event and major bleeding event rates by patient-years, and hazard ratios. During NSAID-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 37.5 per 100 patient-years vs 16.6 per 100 patient-years during anticoagulant use only (hazard ratio [HR], 1.77 [95% CI, 1.46-2.14]). Major bleeding during NSAID-anticoagulant treatment occurred with an event rate of 6.5 per 100 patient-years, compared to 2.0 per 100 patient-years during nonuse (HR, 2.37 [95% CI, 1.51-3.75]). For aspirin-anticoagulant concomitant treatment, clinically relevant bleeding occurred with an event rate of 36.6 per 100 patient-years, compared to 16.9 per 100 patient-years during aspirin nonuse (HR, 1.70 [95% CI, 1.38-2.11]). Major bleeding in aspirin-anticoagulant-treated patients occurred with an event rate of 4.8 per 100 patient-years, compared to 2.2 per 100 patient-years during aspirin nonuse (HR, 1.50 [95% CI, 0.86-2.62]). Increases in risk for clinically relevant and major bleeding were similar for rivaroxaban and enoxaparin-VKA anticoagulation regimens. Among patients with venous thromboembolism receiving anticoagulant therapy, concomitant use of an NSAID or aspirin is associated with an increased risk of clinically relevant and major bleeding.

Percutaneous left atrial appendage occlusion for stroke prevention in patients with atrial fibrillation and contraindication for anticoagulation.

PubMed

Grosset-Janin, D; Barth, E; Bertrand, B; Detante, O

2015-05-01

Stroke, as the third cause of death in developed countries, is a public health issue. Atrial fibrillation is an important cause of ischemic stroke and its prevention is efficient with oral anticoagulation. However, oral anticoagulation can be contraindicated because of hemorrhagic risk related to these treatments. Percutaneous left atrial appendage occlusion is a new alternative of oral anticoagulation for patients with atrial fibrillation and high risk of cardio-embolic stroke but contraindicated for oral anticoagulation. We describe in this paper the procedure of left atrial appendage occlusion with the Amplatzer cardiac plug device, used in our center in Grenoble university hospital, for the first three patients who have been treated with this device. These three patients (one man and two women) have all atrial fibrillation with neurological complication of this arrhythmia, as ischemic stroke. Oral anticoagulation is indicated to prevent another ischemic stroke. However, they all have a high risk of cerebral bleeding for different reasons (cavernomatosis, history of intracerebral hemorrhage and aneurysm of the polygon of Willis). Consequently, they have a high risk of cardio-embolic complication but contraindication for oral anticoagulation. They have been treated by left atrial appendage occlusion with Amplatzer cardiac plug device by percutaneous and trans-septal access. Then, they have been followed by neurologist and cardiologist, with clinical and paraclinical evaluation by echocardiography. Our three first patients have been successfully implanted, without periprocedural complication. No latest adverse event was observed, and particularly no cardiac or neurologic adverse event. The technique of left atrial appendage occlusion is a very interesting and promising technique for ischemic stroke prevention in patient with high risk of cardio-embolic complication because of atrial fibrillation, but high risk of bleeding and contraindication for oral anticoagulation. Because of frequency of both atrial fibrillation and contraindication for oral anticoagulation, occlusion of the left atrial appendage should become an interesting alternative for many patients. However, it remains an invasive procedure and efficacy and indications need to be evaluated in further clinical trials. Risk/benefit ratio must be carefully assessed and compared to that of the new anticoagulant drugs. Copyright © 2015. Published by Elsevier Masson SAS.

Prostate cancer-specific survival among warfarin users in the Finnish Randomized Study of Screening for Prostate Cancer.

PubMed

Kinnunen, Pete T T; Murtola, Teemu J; Talala, Kirsi; Taari, Kimmo; Tammela, Teuvo L J; Auvinen, Anssi

2017-08-29

Venous thromboembolic events (VTE) are common in cancer patients and associated with higher mortality. In vivo thrombosis and anticoagulation might be involved in tumor growth and progression. We studied the association of warfarin and other anticoagulant use as antithrombotic medication and prostate cancer (PCa) death in men with the disease. The study included 6,537 men diagnosed with PCa during 1995-2009. Information on anticoagulant use was obtained from a national reimbursement registry. Cox regression with adjustment for age, PCa risk group, primary therapy and use of other medication was performed to compare risk of PCa death between warfarin users with 1) men using other types of anticoagulants and 2) non-users of anticoagulants. Medication use was analyzed as a time-dependent variable to minimize immortal time bias. In total, 728 men died from PCa during a median follow-up of 9 years. Compared to anticoagulant non-users, post-diagnostic use of warfarin was associated with an increased risk of PCa death (overall HR 1.47, 95% CI 1.13-1.93). However, this was limited to low-dose, low-intensity use. Otherwise, the risk was similar to anticoagulant non-users. Additionally, we found no risk difference between warfarin and other types of anticoagulants. Pre-diagnostic use of warfarin was not associated with the risk of PCa death. We found no reduction in risk of PCa death associated with warfarin use. Conversely, the risk was increased in short-term use, which is probably explained by a higher risk of thrombotic events prompting warfarin use in patients with terminal PCa.

Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies

PubMed Central

Masci, Paul P.; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A.; Gobe, Glenda C.

2017-01-01

Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic. PMID:28777290

Sex and Gender Differences in Thromboprophylactic Treatment of Patients With Atrial Fibrillation After the Introduction of Non-Vitamin K Oral Anticoagulants.

PubMed

Loikas, Desirée; Forslund, Tomas; Wettermark, Björn; Schenck-Gustafsson, Karin; Hjemdahl, Paul; von Euler, Mia

2017-10-15

To examine sex differences in thromboprophylaxis in patients with atrial fibrillation before and after the introduction of non-vitamin K oral anticoagulants, we performed a cross-sectional registry study based on anonymized individual-level patient data of all individuals with a diagnosis of nonvalvular atrial fibrillation (International Classification of Diseases, Tenth Revision code I48) in the region of Stockholm, Sweden (2.2 million inhabitants), in 2011 and 2015, respectively. Thromboprophylaxis improved considerably during the period. During 2007 to 2011, 23,198 men and 18,504 women had an atrial fibrillation diagnosis. In 2011, more men than women (53% men vs 48% women) received oral anticoagulants (almost exclusively warfarin) and more women received aspirin only (35% women vs 30% men), whereas there was no sex difference for no thromboprophylaxis (17%). During 2011 to 2015, 27,237 men and 20,461 women had a diagnosis of atrial fibrillation. Compared with the earlier time period, a higher proportion used oral anticoagulants (71% women vs 70% men), but fewer women ≥80 years received anticoagulants (67% women vs 72% men), more women received aspirin (15% women vs 13% men), and fewer women had no thromboprophylaxis (15% women vs 17% men). Patients with co-morbidities potentially complicating oral anticoagulant use used more oral anticoagulant in 2015 compared with 2011. The sex differences observed in 2011 with fewer women using oral anticoagulants had disappeared in 2015 except in women 80 years and older and in patients with complicated co-morbidity. Copyright © 2017 Elsevier Inc. All rights reserved.

Anticoagulant factor V: factors affecting the integration of novel scientific discoveries into the broader framework.

PubMed

LaBonte, Michelle L

2014-09-01

Since its initial discovery in the 1940s, factor V has long been viewed as an important procoagulant protein in the coagulation cascade. However, in the later part of the 20th century, two different scientists proposed novel anticoagulant roles for factor V. Philip Majerus proposed the first anticoagulant function for factor V in 1983, yet ultimately it was not widely accepted by the broader scientific community. In contrast, Björn Dahlbäck proposed a different anticoagulant role for factor V in 1994. While this role was initially contested, it was ultimately accepted and integrated into the scientific framework. In this paper, I present a detailed historical account of these two anticoagulant discoveries and propose three key reasons why Dahlbäck's anticoagulant role for factor V was accepted whereas Majerus' proposed role was largely overlooked. Perhaps most importantly, Dahlbäck's proposed anticoagulant role was of great clinical interest because the discovery involved the study of an important subset of patients with thrombophilia. Soon after Dahlbäck's 1994 work, this patient population was shown to possess the factor V Leiden mutation. Also key in the ultimate acceptance of the second proposed anticoagulant role was the persistence of the scientist who made the discovery and the interest in and ability of others to replicate and reinforce this work. This analysis of two different yet similar discoveries sheds light on factors that play an important role in how new discoveries are incorporated into the existing scientific framework. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

Venous thromboembolism: role of pharmacists and managed care considerations.

PubMed

Horner, Tuesdy; Mahan, Charles E

2017-12-01

Venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism. Anticoagulation is used in patients with VTE to reduce the risk of recurrent VTE and VTE-related death. The overall incidence of VTE is 1 to 2 per 1000 person-years. Long-term mortality for patients with VTE is poor, with 25% of patients not surviving 7 days and nearly 40% not surviving the first year. Coagulation disorders demand effective anticoagulant therapy to avoid complications, especially recurrent VTE and VTE-related death. For more than 60 years, warfarin has been the cornerstone of therapy for patients requiring anticoagulation and was the sole oral anticoagulant available in the United States until 2010. Since then, the FDA has approved 5 direct-acting oral anticoagulants (DOACs) that inhibit single coagulation factors (factor Xa and thrombin). DOACs provide predictable anticoagulation with fixed dosing, easier perioperative management, no routine laboratory monitoring, and fewer food-drug interactions. However, when choosing DOACs, clinicians must consider several issues in addition to efficacy and safety before employing these therapies, including patient-specific factors, adherence and persistence with therapy, and their cost-effectiveness for clinical use.

Antioxidant and anticoagulant activity of polyphenol and polysaccharides from fermented Sargassum sp.

PubMed

Shobharani, P; Nanishankar, V H; Halami, P M; Sachindra, N M

2014-04-01

The current investigation was carried out with an objective of determining the structural characteristic of polysaccharides extracted from fermented Sargassum sp. to be used as potent natural heparin substitute anticoagulant compound. Sargassum sp. fermented with marine lactic acid bacteria was initially subjected to ethanol precipitation for the recovery of bioactive compounds. Antioxidant activity was maximum in the soluble fraction whereas anticoagulant activity was observed to be high in the precipitate which correlated with the increased polyphenols and total sugars respectively. The precipitate was purified by anion exchange chromatography and the fractions collected were analyzed for total sugars and anticoagulant activity. There was 2.6-3.9-folds increase in anticoagulant activity in the final purified fractions, with a maximum activity in case of sample fermented with Enterococcus faecium (6.7±0.22 IU/mg). Structural elucidation of potential anticoagulant polysaccharide by Fourier Transform Infrared Spectroscopy (FT-IR) and Nuclear Magnetic Resonance (NMR) analysis indicated the presence of alginate rich in mannuronic acid. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel anticoagulants for stroke prevention in patients with atrial fibrillation.

PubMed

Jalota, A; Scarabelli, T M; Saravolatz, L; Bakhsh, M U; Agrawal, P; Jalota, R; Chen-Scarabelli, C; Fuster, V; Halperin, J

2014-06-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia that can potentially result in stroke. Vitamin K antagonists (VKA) like warfarin were for many decades the only oral anticoagulants available for stroke prevention in patients with non-valvular atrial fibrillation (AF) at high risk of stroke. Recently, new oral anticoagulants (NOACS) have been introduced that act via direct inhibition of thrombin (dabigatran) or activated factor X (edoxaban, rivaroxaban and apixaban). Unlike VKAs, these anticoagulants do not require routine INR monitoring and posses favorable pharmacological properties. NOACs act rapidly, and have a stable and predictable dose-related anticoagulant effect with few clinically relevant drug-drug interactions. Phase III trials comparing these agents to warfarin for stroke prevention in patients with non-valvular AF demonstrated that they are at least as efficacious and safe as warfarin. Evolution of clinical guidelines to incorporate the new anticoagulants for stroke prevention in non-valvular AF may result in a reduction in the incidence of AF-related strokes. Safe and effective use of these new drugs in clinical practice requires understanding of their distinct pharmacological properties.

[Analysis of characteristics of acute poisoning caused by various poisons in Guangxi, China].

PubMed

Hu, De-hong; Zhang, Zhen-ming; Liu, Qing-hua; Jiang, Dong-fang

2013-11-01

To investigate the characteristics of acute poisonings caused by various poisons in Guangxi, China. A retrospective investigation was performed in 5859 cases of acute poisonings who were admitted to 63 hospitals in 11 cities, as well as 531 types of poisons involved. The poisons were categorized into 6 groups; each group of cases was stratified by the rural or urban settings, frequency of poisoning, and cause of poisoning to analyze the numbers of cases and constituent ratios. Most types of poisons (68.74%) belonged to drugs (217 types) and pesticides (148 types). Most cases of poisonings (61.63%) were caused by pesticides (n = 2547) and chemicals (n = 1064). Pesticides, poisons of plant origins, and poisons of animal origins were responsible for most of the cases in rural settings; 88.46%, 79.10%, and 66.74% of the cases of these poison categories happened in rural settings. Chemicals, drugs, and other poisons were responsible for most of the cases in urban settings; 70.20%, 61.74%, and 63.73% of the cases of these poison categories happened in urban settings. The numbers of cases in 5-year-poisoning groups were the highest in all categories of poisons, accounting for 85.24%, 88.57%, 55.16%, 70.79%, 68.36%, and 66.44%of cases of respective categories. Most cases of poisonings by chemicals, poisons of animal origin, and other poisons were accident-related (86.24%, 72.66%, and 46.71%of the poison categories). Most cases of poisonings by pesticides and drugs were suicide-related (59.39% and 33.52% of the poison categories). Most cases by poisons of plant origin were caused by accidental ingestion (70.36% of the poison category). Most of the acute poisonings in Guangxi area are caused by pesticides and chemicals; the most common causes of poisoning are accidents, accidental ingestion, and suicide. There are significant differences in the causes of acute poisonings between the urban and rural settings.

[Management of new oral anticoagulants in gastrointestinal bleeding and endoscopy].

PubMed

del Molino, Fátima; Gonzalez, Isabel; Saperas, Esteve

2015-10-01

New oral direct anticoagulants agents are alternatives to warfarin for long-term anticoagulation in a growing number of patients that require long-term anticoagulation for atrial fibrillation, deep venous thrombosis and pulmonary embolism. These new agents with predictable pharmacokinetic and pharmacodynamics profiles offer a favorable global safety profile, but increased gastrointestinal bleeding compared to the vitamin K antagonists. Many gastroenterologists are unfamiliar and may be wary of these newer drugs, since Clinical experience is limited and no specific antidote is available to reverse their anticoagulant effect. In this article the risk of these new agents and, how to manage these agents in both the presence of acute gastrointestinal bleeding and in patients undergoing endoscopic procedures is reviewed. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Anticoagulant management in the cardiovascular setting.

PubMed

Verheugt, Freek W A

2012-02-01

Vitamin K antagonists have been used as oral anticoagulants (OACs) for over five decades, yet their use in real-world practice is problematic primarily because of their narrow therapeutic window, exacerbated by extensive food and drug interactions, necessitating regular coagulation monitoring and dose adjustment. Around half of patients receiving warfarin are within the therapeutic range, exposing them to the dangers of under-anticoagulation (i.e. thrombosis formation) or over-anticoagulation (i.e. bleeding). A new generation of OACs with improved pharmacology promises to revolutionize antithrombotic management. Rivaroxaban, apixaban (both oral direct Factor Xa inhibitors) and dabigatran (a direct thrombin inhibitor) all exhibit predictable anticoagulant responses and few drug-drug interactions and do not require routine coagulation monitoring. © 2011 The Author Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Acute major gastrointestinal bleeding caused by hookworm infection in a patient on warfarin therapy: A case report.

PubMed

Meng, Yu; Lu, FangGen; Shi, Lin; Cheng, MeiChu; Zhang, Jie

2018-03-01

The use of anticoagulants is a contributor to gastrointestinal (GI) bleeding. Most bleeding patients on anticoagulant therapy such as warfarin commonly have basic lesions existing in their GI mucosa. We report a case of major GI bleeding following the use of anticoagulants in a patient with hookworm infection. The patient was diagnosed with nephrotic syndrome with pulmonary embolism. He was treated with anticoagulants and suffered from acute major GI bleeding during the treatment. Capsule endoscopy revealed many hookworms in the lumen of jejunum where fresh blood was seen coming from the mucosa. The patient was successfully rescued and cured with albendazole. Latent hookworm infection can be a cause of massive small-bowel hemorrhage in patients on anticoagulant therapy and anthelmintic treatment is the key to stop bleeding.

Comparative effectiveness of rivaroxaban versus warfarin or dabigatran for the treatment of patients with non-valvular atrial fibrillation.

PubMed

Norby, Faye L; Bengtson, Lindsay G S; Lutsey, Pamela L; Chen, Lin Y; MacLehose, Richard F; Chamberlain, Alanna M; Rapson, Ian; Alonso, Alvaro

2017-09-06

Rivaroxaban is an oral anticoagulant approved in the US for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). We determined the effectiveness and associated risks of rivaroxaban versus other oral anticoagulants in a large real-world population. We selected NVAF patients initiating oral anticoagulant use in 2010-2014 enrolled in MarketScan databases. Rivaroxaban users were matched with warfarin and dabigatran users by age, sex, enrolment date, anticoagulant initiation date, and high-dimensional propensity score. Study endpoints, including ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding, were identified from inpatient diagnostic codes. Multivariable Cox models were used to assess associations between type of anticoagulant and outcomes. The analysis included 44,340 rivaroxaban users matched to 89,400 warfarin and 16,957 dabigatran users (38% female, mean age 70) with 12 months of mean follow-up. Anticoagulant-naïve rivaroxaban initiators, but not those switching from warfarin, had lower risk of ischemic stroke [hazard ratio (HR) (95% confidence interval (CI)): 0.75 (0.62, 0.91)] and ICB [HR (95%CI): 0.55, (0.39, 0.78)] than warfarin users. In contrast, anticoagulant-experienced rivaroxaban initiators had higher risk of GI bleeding than warfarin users [HR (95%CI): 1.55 (1.32, 1.83)]. Endpoint rates were similar when comparing anticoagulant-naïve rivaroxaban and dabigatran initiators, with the exception of higher GI bleeding risk in rivaroxaban users [HR (95%CI) 1.28 (1.06, 1.54)]. There were no significant differences in the risk of MI among the comparison groups. In this large real-world sample of NVAF patients, effectiveness and risks of rivaroxaban versus warfarin differed by prior anticoagulant status, while effectiveness of rivaroxaban versus dabigatran differed in GI bleeding risk.

Changes in hemolymph characteristics of ark shell Scapharaca broughtonii dealt with Vibrio anguillarum challenge in vivo and various of anticoagulants in vitro.

PubMed

Zhou, Liqing; Yang, Aiguo; Liu, Zhihong; Wu, Biao; Sun, Xiujun; Lv, Zhenming; Tian, Ji-Teng; Du, Meirong

2017-02-01

The ark shell Scapharca broughtonii is a commercially important shellfish in China. Alserver's solution (AS), modified Alserver's solution (MAS) and Heparin sodium solution (HSS) are common anticoagulants used for shellfish blood. To observe the immune response mediated by its hemocytes, we challenged in vivo S. broughtonii hemolymph with Vibrio anguillarum and dealt with the following three anticoagulants in vitro: Alserver's solution (AS), modified Alserver's solution (MAS) and Heparin sodium solution (HSS). The methodologies we used were immunostimulation with V. anguillarum, Wright-Giemsa staining, micro-examination, and flow cytometric and hydrolyzing enzyme activity analysis. The results showed that all three types of anticoagulants effectively prevented blood clotting in ark shellfish. The morphology of hemocytes did not significantly change 30 h after anticoagulant treatment, except for the shrinking of hemocytes after administering HSS. The size and permeability of hemocytes changed when treated with the anticoagulants and when stimulated with V. anguillarum. Both alkaline phosphatase (AKP) and acid phosphatase (ACP) in hemocytes and Plasma were measured at different times after they were stimulated with V. anguillarum in HSS and MAS. The AKP enzymatic activity in HSS was somewhat higher than in the MAS anticoagulant, but changes in response to V. anguillarum challenge of enzymatic activity were almost the same in HSS and MAS groups. In conclusion, all three types of anticoagulants may be used for ark shell blood preservation. They all changed the cell-surface characteristics of hemocytes to inhibit clot formation. The AS anticoagulant was appropriate for maintaining white and red cell shapes, while MAS was ideal for retaining throbus cell function. Lastly, HSS was appropriate for maintaining enzymatic activity in hemolymph and function of hemocytes. Following this investigation, we gained insight into the changes in hemolymph characteristic during immune response. Copyright © 2016. Published by Elsevier Ltd.

Anticoagulants and the propagation phase of thrombin generation.

PubMed

Orfeo, Thomas; Gissel, Matthew; Butenas, Saulius; Undas, Anetta; Brummel-Ziedins, Kathleen E; Mann, Kenneth G

2011-01-01

The view that clot time-based assays do not provide a sufficient assessment of an individual's hemostatic competence, especially in the context of anticoagulant therapy, has provoked a search for new metrics, with significant focus directed at techniques that define the propagation phase of thrombin generation. Here we use our deterministic mathematical model of tissue-factor initiated thrombin generation in combination with reconstructions using purified protein components to characterize how the interplay between anticoagulant mechanisms and variable composition of the coagulation proteome result in differential regulation of the propagation phase of thrombin generation. Thrombin parameters were extracted from computationally derived thrombin generation profiles generated using coagulation proteome factor data from warfarin-treated individuals (N = 54) and matching groups of control individuals (N = 37). A computational clot time prolongation value (cINR) was devised that correlated with their actual International Normalized Ratio (INR) values, with differences between individual INR and cINR values shown to derive from the insensitivity of the INR to tissue factor pathway inhibitor (TFPI). The analysis suggests that normal range variation in TFPI levels could be an important contributor to the failure of the INR to adequately reflect the anticoagulated state in some individuals. Warfarin-induced changes in thrombin propagation phase parameters were then compared to those induced by unfractionated heparin, fondaparinux, rivaroxaban, and a reversible thrombin inhibitor. Anticoagulants were assessed at concentrations yielding equivalent cINR values, with each anticoagulant evaluated using 32 unique coagulation proteome compositions. The analyses showed that no anticoagulant recapitulated all features of warfarin propagation phase dynamics; differences in propagation phase effects suggest that anticoagulants that selectively target fXa or thrombin may provoke fewer bleeding episodes. More generally, the study shows that computational modeling of the response of core elements of the coagulation proteome to a physiologically relevant tissue factor stimulus may improve the monitoring of a broad range of anticoagulants.

Impact of a Focused Approach for Discharge Teaching Regarding the Use of Aspirin as Anticoagulant After Joint Replacement Surgery.

PubMed

Wittig-Wells, Deborah; Higgins, Melinda; Davis, Erica; Johnson, Ifeya; Louis, Latalya; Mason, Olga; Samms-McPherson, Jacqueline; Sims, Sandra; Jacob, Ani

2015-01-01

Patient education for the use and administration of aspirin (ASA) as an anticoagulant may be deficient. To pilot a knowledge assessment tool regarding the use of aspirin (ASA) as an anticoagulant and to evaluate the impact of a focused approach for discharge teaching. One-group pretest-posttest pilot study. Convenience sample of patients hospitalized for total knee and total hip arthroplasty. Researcher developed ASA quiz. Focused education on aspirin as an anticoagulant. There was a statistically significant improvement in knowledge (Wilcoxon rank sum test Z = 3.880, p < .001).

[New oral anticoagulant drugs].

PubMed

Berkovits, Alejandro; Aizman, Andrés; Zúñiga, Pamela; Pereira, Jaime; Mezzano, Diego

2011-10-01

Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin K antagonists, whose anticoagulant effect is exerted inhibiting vitamin K epoxide reductase. Warfarin and acenocoumarol are the most commonly used. In the last five years several new drugs for long term anticoagulation have been developed, which can inhibit single clotting factors with the purpose of improving drug therapeutic range and, ideally, minimizing bleeding risks. This review addresses the state of the art on the clinical use of inhibitors of activated factor X and thrombin.

Disadvantages of VKA and requirements for novel anticoagulants.

PubMed

Shameem, Raji; Ansell, Jack

2013-06-01

Vitamin K antagonists have been in wide use for over 70 years. Warfarin, the most commonly used vitamin K antagonist, has been shown to be highly effective in treating and preventing thrombosis. Despite this, warfarin has many disadvantages, which has led to the development of a new class of oral anticoagulants targeted to specific coagulation factors designated as target-specific oral anticoagulants (TSOAs). TSOAs include the thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). This chapter reviews the disadvantages of warfarin and evaluates both the advantages and disadvantages of the new oral anticoagulants. © 2013 Elsevier Ltd. All rights reserved.

Healthcare resources and needs in anticoagulant therapy for patients with nonvalvular atrial fibrillation. SAMOA Study.

PubMed

Barrios, V; Egocheaga-Cabello, M I; Gállego-Culleré, J; Ignacio-García, E; Manzano-Espinosa, L; Martín-Martínez, A; Mateo-Arranz, J; Polo-García, J; Vargas-Ortega, D

2017-05-01

To determine, in the various medical specialties, the healthcare process for anticoagulated patients with nonvalvular atrial fibrillation, to determine the available and necessary resources and to identify potential areas of improvement in the care of these patients. We performed a cross-sectional survey of primary care and specialised physicians involved in the care of anticoagulated patients. The questionnaires referred to the healthcare process, the indication and prescription of anticoagulant therapy and the barriers and deficiencies present for these patients. A total of 893 physicians participated in the study, 437 of whom worked in primary care and 456 of whom were specialists (mostly cardiologists). Forty-two percent of the family doctors indicated that they assessed and prescribed anticoagulant therapy, and 66% performed the regular follow-up of these patients. In both healthcare settings, the physicians noted the lack of standardised protocols. There was also a lack of quality control in the treatment. The role of primary care in managing anticoagulated patients has grown compared with previous reports. The responses of the participating physicians suggest marked gaps in the standardisation of the healthcare process and several areas for improvement in these patients' follow-up. The promotion of training in direct-acting anticoagulant drugs remains pivotal. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Standards of care issues with anticoagulation in real-world populations.

PubMed

2015-01-01

Current guidelines recommend anticoagulants for reducing the risk of stroke in appropriate patients with nonvalvular atrial fibrillation (NVAF) and for the acute treatment of venous thromboembolism (VTE) and the prevention of recurrent VTE. Warfarin is the standard of care for both NVAF and VTE, yet International Normalized Ratio (INR) control remains suboptimal, even in the clinical trial setting. Maintaining INR within the recommended therapeutic range is associated with better outcomes in these distinct populations. In VTE, high rates of recurrence have been reported during the first few weeks of treatment, emphasizing the importance of surveillance during this time and of early optimization of anticoagulation therapy. The NVAF population tends to have more comorbidities and requires longer-term therapy. It is important to keep in mind that real-world patient populations are more complex than those in controlled studies. Patients with multiple comorbidities are particularly challenging, and physicians may focus on clinically urgent issues rather than anticoagulation optimization. Despite the many complexities associated with the use of warfarin, it remains a mainstay of anticoagulation therapy. Aligning financial incentives and improving care coordination are important factors in moving toward better outcomes for patients who need anticoagulation therapy. The increased focus on value-based care and evolving approaches to patient treatment could lead more physicians and payers to consider alternatives to warfarin, including the use of novel oral anticoagulants.

The first pharmacist-managed anticoagulation clinic under a collaborative practice agreement in Qatar: clinical and patient-oriented outcomes.

PubMed

Elewa, H F; AbdelSamad, O; Elmubark, A E; Al-Taweel, H M; Mohamed, A; Kheir, N; Mohamed Ibrahim, M I; Awaisu, A

2016-08-01

Optimal outpatient anticoagulation management requires a systematic and coordinated approach. Extensive evidence regarding the benefits of pharmacist-managed anticoagulation services has been reported in the literature. The quality and outcomes associated with pharmacist-managed anticoagulation clinics under collaborative practice agreements in the Middle East have rarely been reported. The first pharmacist-managed ambulatory anticoagulation clinic in Qatar was launched at Al-Wakrah Hospital in March 2013. The objectives of this study were to: (i) describe the practice model of the clinic, (ii) evaluate the quality of the clinic [i.e. the time in therapeutic range (TTR)] and the clinical outcomes (i.e. the efficacy and safety), and (iii) determine the patients' satisfaction and overall quality of life (QoL). Clinical outcome data were collected through a retrospective chart review of all patients managed from March 2013 to October 2014 at the pharmacist-managed anticoagulation clinic. Furthermore, the patient-oriented outcomes data were prospectively collected using the 24-item Duke Anticoagulation Satisfaction Scale (DASS). Each item was assessed using a 7-point Likert-type scale on which lower scores indicated better QoL and greater satisfaction. The clinical outcome data analyses included 119 patients who were enrolled at the clinic during the 19-month study period. The mean number of international normalized ratio (INR) tests/month was 65 ± 9, the average testing frequency was 2·7 ± 1·6 weeks, and the average %TTR was 76·8 ± 22·9%. There was one major bleeding event (0·67%/year), 12 minor bleeding events (8%/year) and two thromboembolic events (1·35%/year) recorded during the study period. Of the 119 patients, 50 participated in the satisfaction and QoL survey. The median (IQR) total QoL score of these subjects was 63 (48) (minimum-maximum achievable score: 24-168). Seventy-six per cent of the patients indicated 'a lot to very much' in terms of their overall satisfaction with the anticoagulation treatment. The participants who were naïve to anticoagulation treatment reported a significantly greater satisfaction and better QoL than the experienced patients [58 (44) vs. 82 (59); P = 0·009]. These findings provide early evidence that the patients who were managed at a pharmacy-based anticoagulation clinic in an evolving healthcare system experienced optimal anticoagulation management. © 2016 John Wiley & Sons Ltd.

Anticoagulation Therapy for Venous Thromboembolism in the Real World　- From the COMMAND VTE Registry.

PubMed

Yamashita, Yugo; Morimoto, Takeshi; Amano, Hidewo; Takase, Toru; Hiramori, Seiichi; Kim, Kitae; Konishi, Takashi; Akao, Masaharu; Kobayashi, Yohei; Inoue, Takeshi; Oi, Maki; Izumi, Toshiaki; Takahashi, Kotaro; Tada, Tomohisa; Chen, Po-Min; Murata, Koichiro; Tsuyuki, Yoshiaki; Sakai, Hiroshi; Saga, Syunsuke; Sasa, Tomoki; Sakamoto, Jiro; Yamada, Chinatsu; Kinoshita, Minako; Togi, Kiyonori; Ikeda, Tomoyuki; Ishii, Katsuhisa; Kaneda, Kazuhisa; Mabuchi, Hiroshi; Otani, Hideo; Takabayashi, Kensuke; Takahashi, Mamoru; Shiomi, Hiroki; Makiyama, Takeru; Ono, Koh; Kimura, Takeshi

2018-04-25

Venous thromboembolism (VTE) has a long-term risk of recurrence, which can be prevented by anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE between January 2010 and August 2014. The entire cohort was divided into the transient risk (n=855, 28%), unprovoked (n=1,477, 49%), and cancer groups (n=695, 23%). The rate of anticoagulation discontinuation was highest in the cancer group (transient risk: 37.3% vs. unprovoked: 21.4% vs. cancer: 43.5% at 1 year, P<0.001). The cumulative 5-year incidences of recurrent VTE, major bleeding and all-cause death were highest in the cancer group (recurrent VTE: 7.9% vs. 9.3% vs. 17.7%, P<0.001; major bleeding: 9.0% vs. 9.4% vs. 26.6%, P<0.001; and all-cause death: 17.4% vs. 15.3% vs. 73.1%, P<0.001). After discontinuation of anticoagulation therapy, the cumulative 3-year incidence of recurrent VTE was lowest in the transient risk group (transient risk: 6.1% vs. unprovoked: 15.3% vs. cancer: 13.2%, P=0.001). The cumulative 3-year incidence of recurrent VTE beyond 1 year was lower in patients on anticoagulation than in patients off anticoagulation at 1 year in the unprovoked group (on: 3.7% vs. off: 12.2%, P<0.001), but not in the transient risk and cancer groups (respectively, 1.6% vs. 2.5%, P=0.30; 5.6% vs. 8.6%, P=0.44). The duration of anticoagulation therapy varied widely in discordance with current guideline recommendations. Optimal duration of anticoagulation therapy should be defined according to the risk of recurrent VTE and bleeding as well as death.

The "Janus face" of the thrombin binding aptamer: Investigating the anticoagulant and antiproliferative properties through straightforward chemical modifications.

PubMed

Esposito, Veronica; Russo, Annapina; Amato, Teresa; Vellecco, Valentina; Bucci, Mariarosaria; Mayol, Luciano; Russo, Giulia; Virgilio, Antonella; Galeone, Aldo

2018-02-01

The thrombin binding aptamer (TBA) is endowed with both anticoagulant and antiproliferative activities. Its chemico-physical and/or biological properties can be tuned by the site-specific replacement of selected residues. Four oligodeoxynucleotides (ODNs) based on the TBA sequence (5'-GGTTGGTGTGGTTGG-3') and containing 2'-deoxyuridine (U) or 5-bromo-2'-deoxyuridine (B) residues at positions 4 or 13 have been investigated by NMR and CD techniques. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay) have been tested and compared with two further ODNs containing 5-hydroxymethyl-2'-deoxyuridine (H) residues in the same positions, previously investigated. The CD and NMR data suggest that all the investigated ODNs are able to form G-quadruplexes strictly resembling that of TBA. The introduction of B residues in positions 4 or 13 increases the melting temperature of the modified aptamers by 7 °C. The replacement of thymidines with U in the same positions results in an enhanced anticoagulant activity compared to TBA, also at low ODN concentration. Although all ODNs show antiproliferative properties, only TBA derivatives containing H in the positions 4 and 13 lose the anticoagulant activity and remarkably preserve the antiproliferative one. All ODNs have shown antiproliferative activities against two cancer cell lines but only those with U and B are endowed with anticoagulant activities similar or improved compared to TBA. The appropriate site-specific replacement of the residues in the TT loops of TBA with commercially available thymine analogues is a useful strategy either to improve the anticoagulant activity or to preserve the antiproliferative properties by quenching the anticoagulant ones. Copyright © 2017 Elsevier Inc. All rights reserved.

Rapid bedside coagulometry prior to urgent neurosurgical procedures in anticoagulated patients.

PubMed

Beynon, Christopher; Jakobs, Martin; Rizos, Timolaos; Unterberg, Andreas W; Sakowitz, Oliver W

2014-01-01

With the increased use of oral anticoagulation with vitamin K antagonists, emergency physicians encounter a growing number of patients requiring a rapid reversal of anticoagulant effects in order to perform urgent surgical procedures. Initiation of these procedures can be delayed because the coagulation status has to be assessed through examination of blood samples in central laboratories (CL). This delay may lead to negative effects, especially in potentially life-threatening conditions such as intracranial haemorrhage. Point-of-care (POC) devices for assessment of international normalized ratio (POC INR) have improved the management of anticoagulation therapy in the outpatient setting. The use of these devices may also have beneficial effects in the treatment of anticoagulated patients requiring urgent neurosurgical procedures. The primary aim of this study was to analyse the potential of POC-guided assessment of INR to reduce time to potentially life-saving neurosurgery in this setting. Feasibility and accuracy as well as the gain of time through the use of this device were analysed. The POC coagulometer CoaguChek XS(®) was used in 17 patients with a history of anticoagulant use and a condition requiring urgent anticoagulant reversal prior to neurosurgical procedures (burr-hole trepanation: n = 8, craniotomy: n = 7, laminectomy: n = 2). No technical difficulties occurred and rapid assessment of INR was achieved in all cases within 2 min. POC INR values correlated well with CL INR assessment with a mean INR deviation of 0.036 ± 0.12. The mean gain of time through the use of the POC INR device compared with CL assessment of INR was 47 ± 6 min (range: 37-61 min). Our initial experiences with a POC INR device in anticoagulated patients undergoing urgent neurosurgical procedures demonstrate that its use may contribute to an improved management of these patients.

Economic evaluation of a randomized controlled trial of pharmacist-supervized patient self-testing of warfarin therapy.

PubMed

Gallagher, J; Mc Carthy, S; Woods, N; Ryan, F; O' Shea, S; Byrne, S

2015-02-01

The increase in numbers of patients requiring oral anti-coagulation testing in outpatient clinics has focused attention on alternative flexible systems of anti-coagulation management. One option is pharmacist led patient self-testing (PST) of international normalised ratio (INR) levels. PST has demonstrated improvements in anti-coagulation control, but its cost-effectiveness is inconclusive. This study reports the first cost-effectiveness evaluation of a randomized controlled trial of an automated direct-to-patient expert system, enabling remote and effective management of patients on oral anti-coagulation therapy. We conducted an economic evaluation alongside a randomised controlled trial investigating a pharmacist led PST method. The primary outcome was to determine the cost effectiveness of PST in comparison with usual care (management in a hospital based anti-coagulation clinic). Long term anti-coagulation patients were recruited to a 6 month cross over study between PST and routine care in an anti-coagulation clinic. Economic evaluation was from the healthcare payer perspective. On a per patient basis over a 6 month period, PST resulted in an incremental cost of €59.08 in comparison with routine care. Patients achieved a significantly higher time in therapeutic range (TTR) during the PST arm in comparison with routine care, (72 ± 19.7% vs. 59 ± 13.5%). Overall cost of managing a patient through pharmacist supervised PST for a 6 month period is €226.45. Additional analysis of strategies from a societal perspective indicated that PST was the dominant strategy. Pharmacist led patient self-testing is a viable method of management. It provides significant increases in anti-coagulation control for a minimal increase in cost. © 2014 John Wiley & Sons Ltd.

Hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation.

PubMed

Marsh, E B; Llinas, R H; Hillis, A E; Gottesman, R F

2013-06-01

Intracerebral hemorrhage (ICH) can occur in patients following acute ischaemic stroke in the form of hemorrhagic transformation, and results in significant long-term morbidity and mortality. Anticoagulation theoretically increases risk. We evaluated stroke patients with an indication for anticoagulation to determine the factors associated with hemorrhagic transformation. Three-hundred and forty-five patients with ICD-9 codes indicating: (i) acute ischaemic stroke; and (ii) an indication for anticoagulation were screened. One-hundred and twenty-three met inclusion criteria. Data were collected retrospectively. Neuroimaging was reviewed for infarct volume and evidence of ICH. Hemorrhages were classified as: hemorrhagic conversion (petechiae) versus intracerebral hematoma (a space occupying lesion); symptomatic versus asymptomatic. Using multivariable logistic regression, we determined the hypothesized factors associated with intracerebral bleeding. Age [odds ratio (OR) = 1.50 per 10-year increment, 95% confidence interval (CI) 1.07-2.08], infarct volume (OR = 1.10 per 10 ccs, 95% CI 1.06-1.18) and worsening category of renal impairment by estimated glomerular filtration rate (eGFR; OR = 1.95, 95% CI 1.04-3.66) were predictors of hemorrhagic transformation. Ninety- nine out of 123 patients were anticoagulated. Hemorrhage rates of patients on and off anticoagulation did not differ (25.3% vs. 20.8%; P = 0.79); however, all intracerebral hematomas (n = 7) and symptomatic bleeds (n = 8) occurred in the anticoagulated group. The risk of hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation is multifactorial, and most closely associated with an individual's age, infarct volume and eGFR. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of warfarin anticoagulation control.

PubMed

Janzic, Andrej; Kos, Mitja

2015-04-01

Vitamin K antagonists, such as warfarin, are standard treatments for stroke prophylaxis in patients with atrial fibrillation. Patient outcomes depend on quality of warfarin management, which includes regular monitoring and dose adjustments. Recently, novel oral anticoagulants (NOACs) that do not require regular monitoring offer an alternative to warfarin. The aim of this study was to evaluate whether cost effectiveness of NOACs for stroke prevention in atrial fibrillation depends on the quality of warfarin control. We developed a Markov decision model to simulate warfarin treatment outcomes in relation to the quality of anticoagulation control, expressed as percentage of time in the therapeutic range (TTR). Standard treatment with adjusted-dose warfarin and improved anticoagulation control by genotype-guided dosing were compared with dabigatran, rivaroxaban, apixaban and edoxaban. The analysis was performed from the Slovenian healthcare payer perspective using 2014 costs. In the base case, the incremental cost-effectiveness ratio for apixaban, dabigatran and edoxaban was below the threshold of €25,000 per quality-adjusted life-years compared with adjusted-dose warfarin with a TTR of 60%. The probability that warfarin was a cost-effective option was around 1%. This percentage rises as the quality of anticoagulation control improves. At a TTR of 70%, warfarin was the preferred treatment in half the iterations. The cost effectiveness of NOACs for stroke prevention in patients with nonvalvular atrial fibrillation who are at increased risk for stroke is highly sensitive to warfarin anticoagulation control. NOACs are more likely to be cost-effective options in settings with poor warfarin management than in settings with better anticoagulation control, where they may not represent good value for money.

Cardiac arrest due to left circumflex coronary artery embolism as a complication of subtherapeutic oral anticoagulation in a patient with mitral and aortic mechanical valve prostheses

PubMed Central

Protasiewicz, Marcin; Gajek, Jacek; Mysiak, Andrzej

2013-01-01

We report a case of a 65-year-old female patient after replacement of aortic and mitral valve with mechanical prostheses and implantation of a pacemaker hospitalized in our clinic due to acute coronary syndrome complicated with cardiac arrest due to ventricular fibrillation. The electrocardiogram performed on admission showed signs of myocardial infarction with concomitant ventricular pacing. After successful resuscitation the coronary angiography was performed, which showed occlusion of the left circumflex artery (LCx) by thrombus. On the basis of intravascular ultrasound imaging the presence of vulnerable plaque, parietal thrombus and dissection of LCx were excluded. It suggested that occlusion of the LCx resulted from its embolism by left-sided heart thrombus due to subtherapeutic oral anticoagulation. In this case suboptimal anticoagulation was partially iatrogenic. Two weeks before the patient had been given vitamin K intravenously due to indeterminable international normalized ratio (INR) level, which caused transient resistance to oral anticoagulants. This case report illustrates tragic difficulties in the treatment with vitamin K antagonists, which concern as many as 2/3 of anticoagulated patients. These troubles contributed to the search for new, more efficient and safer anticoagulants. There are two classes of new oral anticoagulant drugs, which do not require monitoring of coagulation: direct thrombin inhibitors (e.g. dabigatran) and factor Xa inhibitors (e.g. rivaroxaban). In spite of their proven efficacy in the prevention of ischaemic stroke related to atrial fibrillation and prevention or treatment of deep vein thrombosis and pulmonary embolism, the use of new oral anticoagulants for the treatment of patients with mechanical valve prostheses needs further research. PMID:24570697

Cardiac arrest due to left circumflex coronary artery embolism as a complication of subtherapeutic oral anticoagulation in a patient with mitral and aortic mechanical valve prostheses.

PubMed

Protasiewicz, Marcin; Rojek, Aleksandra; Gajek, Jacek; Mysiak, Andrzej

2013-01-01

We report a case of a 65-year-old female patient after replacement of aortic and mitral valve with mechanical prostheses and implantation of a pacemaker hospitalized in our clinic due to acute coronary syndrome complicated with cardiac arrest due to ventricular fibrillation. The electrocardiogram performed on admission showed signs of myocardial infarction with concomitant ventricular pacing. After successful resuscitation the coronary angiography was performed, which showed occlusion of the left circumflex artery (LCx) by thrombus. On the basis of intravascular ultrasound imaging the presence of vulnerable plaque, parietal thrombus and dissection of LCx were excluded. It suggested that occlusion of the LCx resulted from its embolism by left-sided heart thrombus due to subtherapeutic oral anticoagulation. In this case suboptimal anticoagulation was partially iatrogenic. Two weeks before the patient had been given vitamin K intravenously due to indeterminable international normalized ratio (INR) level, which caused transient resistance to oral anticoagulants. This case report illustrates tragic difficulties in the treatment with vitamin K antagonists, which concern as many as 2/3 of anticoagulated patients. These troubles contributed to the search for new, more efficient and safer anticoagulants. There are two classes of new oral anticoagulant drugs, which do not require monitoring of coagulation: direct thrombin inhibitors (e.g. dabigatran) and factor Xa inhibitors (e.g. rivaroxaban). In spite of their proven efficacy in the prevention of ischaemic stroke related to atrial fibrillation and prevention or treatment of deep vein thrombosis and pulmonary embolism, the use of new oral anticoagulants for the treatment of patients with mechanical valve prostheses needs further research.

Antithrombotic treatment and the risk of death and stroke in patients with atrial fibrillation and a CHADS2 score=1.

PubMed

Gorin, Laurent; Fauchier, Laurent; Nonin, Emilie; de Labriolle, Axel; Haguenoer, Ken; Cosnay, Pierre; Babuty, Dominique; Charbonnier, Bernard

2010-04-01

In patients with atrial fibrillation (AF) and an intermediate risk of stroke (CHADS2 score =1), available evidence from clinical trials is inconclusive and the present guidelines for the management of AF indicate that the choice between oral anticoagulant and aspirin in these patients is open. Our goal was to evaluate whether, in patients with AF and only one moderate risk factor for thromboembolism, treatment with an oral anticoagulant is appreciably more beneficial than treatment with an antiplatelet agent. Among 6,517 unselected patients with AF, 1,012 of them (15.5%) had a CHADS2 score of 1 and were liable to treatment with an antiplatelet agent or an anticoagulant. An oral anticoagulant was prescribed for 606 patients (59.9%) and an antiplatelet agent or no antithrombotic treatment for 406 (40.1%). During follow-up (median=793 days, interquartile range=1,332 days), 105 deaths (10.4%) and 19 strokes (1.9%) were recorded. The administration of an anticoagulant was associated with a lower rate of events (relative risk=0.42, 95% confidence interval 0.29-0.60, p<0.0001) than when no anticoagulant was prescribed. Results remained similar after adjustment for age and other confounding factors. In contrast, prescription of an antiplatelet agent was not associated with a lower risk of events. Factors independently associated with an increased risk of events were older age (p<0.0001), concomitant heart failure (p=0.0002), diabetes (p=0.0025), lack of prescription of an anticoagulant (p<0.0001) and permanent AF (p=0.04). Thus, prescription of an anticoagulant is independently associated with a decreased risk of death or stroke among patients with AF and a CHADS2 score =1.

Progressively Worsening Premature Coronary Artery Disease: Adding Anticoagulation Stabilizes-Reverses Clinical Symptomatic Disease Progression in Thrombophilic-Atherothrombotic Patients: A Pilot Study.

PubMed

Rothschild, Matan; Jetty, Vybhav; Mahida, Christopher; Wang, Ping; Prince, Marloe; Goldenberg, Naila; Glueck, Charles J

2017-11-01

In 35 patients with 116 severe premature cardiovascular disease (CVD) events (median age: 48 years), 14 having worsening CVD despite maximal intervention, we evaluated thrombophilia and speculated that anticoagulation might arrest-reverse progressive thrombophilic-atherothrombotic CVD. Thrombophilia-hypofibrinolysis in the 35 patients was compared to 110 patients with venous thromboembolism (VTE) without CVD and to 110 healthy normal controls. Efficacy-safety of anticoagulation was prospectively assessed in 14 of the 35 patients whose CVD worsened over 2 years despite maximal medical-surgical intervention. At entry on maximally tolerated lipid-lowering therapy, median low-density lipoprotein was 88 mg/dL. Measures of thrombophilia-hypofibrinolysis in the 35 cases differed from 110 VTE controls only for the lupus anticoagulant, present in 6 (21%) of 28 cases versus 4 (4%) of 91 VTE controls ( P = .01), and for high anticardiolipin antibodies (ACLAs) immunoglobulin G, 5 (14%) of 35 cases versus 4 of 108 VTE controls (4%), P = .04. The 14 patients who were anticoagulated differed from 110 VTE controls only for the lupus anticoagulant, 38% versus 4%, P = .001, and for high lipoprotein (a), 46% versus 17%, P = .028, respectively. The 14 patients with atherothrombosis having inexorably worsening CAD despite maximal medical-surgical therapy were anticoagulated for 6.5 years (median), with clinical CVD progression arrested in 12 (86%), and all 12 became asymptomatic. In the 35 patients with premature CVD, thrombophilia was pervasive, comparable to or more severe than in VTE controls without CVD. When CVD progressively worsens despite maximal intervention, thrombophilia and atherosclerosis (atherothrombosis) are commonly concurrent, and the downhill course of CVD may be arrested-stabilized by anticoagulation.

Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review.

PubMed

Thibault, Nathan; Morrill, Amanda M; Willett, Kristine C

The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants, the primary adverse event (AE) associated with dabigatran is bleeding. Until the FDA approval of idarucizumab, there had been no reversal agent for dabigatran-induced anticoagulation in patients with life-threatening or uncontrollable bleeding, or those requiring emergent procedures. The primary purpose of this review is to summarize the safety and efficacy of idarucizumab, a monoclonal antibody fragment, and its use as a reversal agent for dabigatran. A literature search was conducted through MEDLINE (1946 to November week 1 2015) and Embase (1980-2015 week 46) using the search term idarucizumab. Clinicaltrials.gov was consulted for a comprehensive list of ongoing and completed studies. Additional studies were identified through bibliographical citations. Clinical trials in animals and humans published in English evaluating the safety and efficacy of idarucizumab for reversal of anticoagulant treatment with dabigatran were included for review. Idarucizumab has been shown to significantly reverse the anticoagulant effects of dabigatran in both healthy volunteers and patients requiring a reversal agent because of either overt bleeding or an emergency surgery or invasive procedure. The most common AEs were headache, nasopharyngitis, back pain, skin irritation, hypokalemia, delirium, constipation, pyrexia, and pneumonia. Deaths reported in idarucizumab studies were attributed to either the index event or a preexisting comorbidity. Most adverse effects were minor, but 21 serious AEs have been reported in the published data including thrombotic events. Given the increased use of direct oral anticoagulants, such as dabigatran, a need for specific reversal agents exists. Idarucizumab has been shown to be safe and effective in the reversal of dabigatran-induced anticoagulation in patients requiring emergent or urgent surgery or in patients with severe bleeding.

Safety of Endovascular Intervention for Stroke on Therapeutic Anticoagulation: Multicenter Cohort Study and Meta-Analysis.

PubMed

Kurowski, Donna; Jonczak, Karin; Shah, Qaisar; Yaghi, Shadi; Marshall, Randolph S; Ahmad, Haroon; McKinney, James; Torres, Jose; Ishida, Koto; Cucchiara, Brett

2017-05-01

Intravenous (IV) tissue plasminogen activator (tPA) is contraindicated in therapeutically anti-coagulated patients. Such patients may be considered for endovascular intervention. However, there are limited data on its safety. We performed a multicenter retrospective study of patients undergoing endovascular intervention for acute ischemic stroke while on therapeutic anticoagulation. We compared the observed rate of National Institute of Neurological Disorders and Stroke defined symptomatic intracerebral hemorrhage (sICH) with risk-adjusted historical control rates of sICH after IV tPA using weighted averages of the hemorrhage after thrombolysis (HAT) and Multicenter Stroke Survey (MSS) prediction scores. We also performed a metaanalysis of studies assessing risk of sICH with endovascular intervention in patients on anticoagulation. Of 94 cases, mean age was 73 years and median National Institutes of Health Stroke Scale was 19. Anticoagulation consisted of warfarin (n = 51), dabigatran (n = 6), rivaroxaban (n = 13), apixaban (n = 1), IV heparin (n = 19), low molecular weight heparin (n = 3), and combined warfarin and IV heparin (n = 3). sICH was seen in 7 patients (7%, 95% confidence interval 4-15), all on warfarin. Predicted sICH rates for the cohort based on HAT and MSS scoring were 12% and 7%, respectively. Meta-analysis of 6 studies showed no significant difference in sICH between patients undergoing endovascular intervention on anticoagulation and comparator groups. Endovascular intervention in subjects on therapeutic anticoagulation appears reasonably safe, with a sICH rate similar to patients not on anticoagulation receiving IV tPA. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Thrombophilia and Recurrent Pregnancy Loss

PubMed Central

Abu-Heija, Adel

2014-01-01

The association between thrombophilia and recurrent pregnancy loss (RPL) has become an undisputed fact. Thorombophilia creates a hypercoaguable state which leads to arterial and/or venous thrombosis at the site of implantation or in the placental blood vessels. Anticoagulants are an effective treatment against RPL in women with acquired thrombophilia due to antiphospholipid syndrome. The results of the use of anticoagulants for treating RPL in women with inherited thrombophilia (IT) are encouraging, but recently four major multicentre studies have shown that fetal outcomes (determined by live birth rates) may not be as favourable as previously suggested. Although the reported side-effects for anticoagulants are rare and usually reversible, the current recommendation is not to use anticoagulants in women with RPL and IT, or for those with unexplained losses. This review examines the strength of the association between thrombophilia and RPL and whether the use of anticoagulants can improve fetal outcomes. PMID:24516750

Decision-making interventions to stop the global atrial fibrillation-related stroke tsunami.

PubMed

Cerasuolo, Joshua O; Montero-Odasso, Manuel; Ibañez, Agustin; Doocy, Shannon; Lip, Gregory Yh; Sposato, Luciano A

2017-04-01

Atrial fibrillation affects 33.5 million people worldwide and its prevalence is expected to double by 2050 because of the aging population. Atrial fibrillation confers a 5-fold higher risk of ischemic stroke compared to sinus rhythm. We present our view of the role of shared medical decision-making to combat global underutilization of oral anticoagulation for stroke prevention in atrial fibrillation patients. Oral anticoagulation underuse is widespread as it is present within atrial fibrillation patients of all risk strata and in countries across all income levels. Reasons for oral anticoagulation underuse include but are probably not limited to poor risk stratification, over-interpretation of contraindications, and discordance between physician prescription preferences and actual administration. By comparing a catastrophic event to the consequences of atrial fibrillation related strokes, it may help physicians and patients understand the negative outcomes associated with oral anticoagulation under-utilization and the magnitude to which oral anticoagulations neutralize atrial fibrillation burden.

Conservative management of neonatal cerebral sinovenous thrombosis with coexisting thrombophilia.

PubMed

Khatri, Vidushi; Chan, Anthony K C; Stein, Nina; Paes, Bosco; Bhatt, Mihir

2018-06-01

: Neonatal cerebral sinovenous thrombosis (CSVT) comprises approximately 50% of all pediatric-related CSVT. Although guidelines support anticoagulation in pediatric CSVT, the role of anticoagulation in neonatal CSVT remains controversial. This case report details the course of a neonate diagnosed with extensive CSVT and concurrent bilateral thalamic and intraventricular hemorrhage. Due to existing hemorrhage at the time of diagnosis, anticoagulation therapy was not administered. Despite coexisting protein C and antithrombin deficiency, CSVT resolved spontaneously, and neurodevelopmental follow-up after 13 years suggests a good prognosis. Although our case had a positive outcome, the association between the use of anticoagulation with concurrent hemorrhage and long-term outcome in neonatal CSVT has not been investigated in prospective studies to firmly guide optimum treatment. Current literature and guidelines for the treatment of neonatal CSVT are reviewed in this article. Until robust studies are available, expert opinion recommends anticoagulation in a stable neonate with CSVT.

Mild brain injury and anticoagulants: Less is enough.

PubMed

Campiglio, Laura; Bianchi, Francesca; Cattalini, Claudio; Belvedere, Daniela; Rosci, Chiara Emilia; Casellato, Chiara Livia; Secchi, Manuela; Saetti, Maria Cristina; Baratelli, Elena; Innocenti, Alessandro; Cova, Ilaria; Gambini, Chiara; Romano, Luca; Oggioni, Gaia; Pagani, Rossella; Gardinali, Marco; Priori, Alberto

2017-08-01

Despite the higher theoretical risk of traumatic intracranial hemorrhage (ICH) in anticoagulated patients with mild head injury, the value of sequential head CT scans to identify bleeding remains controversial. This study evaluated the utility of 2 sequential CT scans at a 48-hour interval (CT1 and CT2) in patients with mild head trauma (Glasgow Coma Scale 13-15) taking oral anticoagulants. We retrospectively evaluated the clinical records of all patients on chronic anticoagulation treatment admitted to the emergency department for mild head injury. A total of 344 patients were included, and 337 (97.9%) had a negative CT1. CT2 was performed on 284 of the 337 patients with a negative CT1 and was positive in 4 patients (1.4%), but none of the patients developed concomitant neurologic worsening or required neurosurgery. Systematic routine use of a second CT scan in mild head trauma in patients taking anticoagulants is expensive and clinically unnecessary.

[Epidemiological analysis for Quzhou pesticide poisoning of year 2008 to 2010].

PubMed

Zhao, Shi-guang; Liu, Si-feng

2012-09-01

To provide scientific evidence of making measures for prevention of pesticide poisoning, the investigation on the condition of pesticide poisoning was carried out in Quzhou. Registration data of pesticide poisoning from 2008 to 2010 in Quzhou were collected and statistically analyzed by SPSS 12.0. During the three years, there were 1222 cases reported for pesticide poisoning. Among them, the number of occupational poisoning was 225 (1 case died), with fatality rate of 0.44%. The number of non-occupational poisoning was 997 (77 cases died), and its fatality rate was 7.72% . The incidence of occupational poisoning and non-occupational poisoning accounted for 18.4% and 81.6% respectively. Male patients were in the majority in occupational pesticides poisoning (accounting for 76.4%), female patients in non-occupational poisoning (accounting for 52.1%). The pesticide poisoning mainly occurred from July to September. Occupational poisoning and non-occupational poisoning cases mainly concentrated in over 65 age group, accounting for 36.0% (81 cases) and 26.3% (262 cases) respectively. Insecticide ranks the first in the terms of total poisoning cases caused by pesticide, and organophosphate poisoning ranks the first in all insecticides. Pesticides poisoning has badly threatened the public health in Quzhou, attention should be paid to non-occupational poisoning. The pesticides poisoning was mainly caused by organophosphate insecticides.

Epidemiology and characteristics of acute poisoning treated at an emergency center.

PubMed

Chen, Feng; Wen, Jun-Ping; Wang, Xiao-Ping; Lin, Qing-Ming; Lin, Cai-Jing

2010-01-01

Acute poisoning is frequently encountered at emergency department. This study was to investigate the epidemiology and characteristics of patients with acute poisoning who were treated at the Emergency Center, Fujian Provincial Hospital, China. We retrospectively analyzed the gender, age, causes of poisoning, types of poisons, poisoning route, emergency diagnoses, outcomes, and prognoses of these patients. Altogether 2867 patients with acute poisoning were treated from January 2004 to December 2009. The ratio of male to female was 1:1.04, and their average age was 33.8 years. Of the 2867 patients, 76.39% were between 18 and 40 years old. The incidence of acute poisoning was as high as 11.33% in January each year. The incidence of poisoning was in a descending order: alcohol poisoning (54.55%), medication poisoning (25.95%), pesticide poisoning (5.65%), and drug poisoning (4.88%). Most (56.44%) of the patients with drug poisoning were under 25 years and their mean age was significantly lower than that of patients with medication poisoning or alcohol poisoning (P < 0.01). Approximately 69.54% of the patients were followed up after emergency treatment, 30.39% were hospitalized, and four patients died. Acute poisoning is largely alcohol poisoning and medication poisoning in a city. The emergency green channel "pre-hospital emergency care-emergency department-hospital treatment" can significantly improve the survival rate of patients with acute poisoning.

Cardiac Tamponade Associated with Rivaroxaban.

PubMed

Boone, Stephen

2015-07-01

Rivaroxaban is an oral anticoagulant approved for prevention of stroke, as well as for the treatment and prevention of venous thromboembolic disease. Hemopericardium is a serious complication of anticoagulant use, which has been reported with oral vitamin-K antagonists and newer oral anticoagulants. At the time of this report, to my knowledge, there are no published reports of hemorrhagic effusion leading to tamponade associated with a Factor Xa Inhibitor. I report a case of hemopericardium with associated tamponade in a patient who developed pericarditis while being treated with Rivaroxaban. The case highlights an important adverse effect of a newer anticoagulant, as well as the particular dangers of medication co-administration in the elderly.

Early anticoagulation therapy for severe burns complicated by inhalation injury in a rabbit model

PubMed Central

Fu, Zhong-Hua; Guo, Guang-Hua; Xiong, Zhen-Fang; Liao, Xincheng; Liu, Ming-Zhuo; Luo, Jinhua

2017-01-01

The aim of the present study was to determine the effects of early anticoagulation treatment on severe burns complicated by inhalation injury in a rabbit model. Under anesthetization, an electrical burns instrument (100°C) was used to scald the backs of rabbits for 15 sec, which established a 30% III severe burns model. Treatment of the rabbits with early anticoagulation effectively improved the severe burns complicated by inhalation injury-induced lung injury, reduced PaO2, PaCO2 and SPO2 levels, suppressed the expression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6, and increased the activity of IL-10. In addition, it was found that early anticoagulation treatment effectively suppressed the activities of caspase-3 and caspase-9, upregulated the protein expression of vascular endothelial growth factor (VEGF) and decreased the protein expression of protease-activated receptor 1 (PAR1) in the severe burns model. It was concluded that early anticoagulation treatment affected the severe burns complicated by inhalation injury in a rabbit model through the upregulation of VEGF and downregulation of PAR1 signaling pathways. Thus, early anticoagulation is a potential therapeutic option for severe burns complicated by inhalation injury. PMID:28944866

New developments in pediatric venous thromboembolism and anticoagulation, including the target-specific oral anticoagulants.

PubMed

Lyle, Courtney A; Sidonio, Robert F; Goldenberg, Neil A

2015-02-01

Pediatric venous thromboembolism (VTE) can affect children of all ages, requiring considerable pharmacologic intervention and is often associated with significant morbidity. Current research efforts are directed toward the development of risk-stratified VTE prevention strategies employing pharmacologic thromboprophylaxis, the optimization of conventional anticoagulation, and the investigation of the safety and efficacy of target-specific oral anticoagulants (TSOACs) in children. Recent research has considerably improved the understanding of risk factors of hospital-acquired VTE and how these factors may be employed in risk-stratified paradigms for VTE prevention in children. Additional insight has been gained in the optimization of conventional anticoagulants in special populations such as neonates and children with inflammatory conditions, and in improving the overall safety and compliance with periprocedural anticoagulation and the use of home International Normalized Ratio monitoring. Furthermore, the use of TSOACs has been described in children and is the focus of numerous ongoing clinical trials that are evaluating the safety and efficacy of these agents in children with VTE. Identification of hospital-acquired VTE risk factors may inform pediatric VTE prevention strategies. Although initial use of TSOACs may be promising, investigation of safety and efficacy in children is still underway.

Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding.

PubMed

Parks, Anna L; Fang, Margaret C

2017-07-01

Anticoagulant medications are frequently used to prevent and treat thromboembolic disease. However, the benefits of anticoagulants must be balanced with a careful assessment of the risk of bleeding complications that can ensue from their use. Several bleeding risk scores are available, including the Outpatient Bleeding Risk Index, HAS-BLED, ATRIA, and HEMORR 2 HAGES risk assessment tools, and can be used to help estimate patients' risk for bleeding on anticoagulants. These tools vary by their individual risk components and in how they define and weigh clinical factors. However, it is not yet clear how best to integrate bleeding risk tools into clinical practice. Current bleeding risk scores generally have modest predictive ability and limited ability to predict the most devastating complication of anticoagulation, intracranial hemorrhage. In clinical practice, bleeding risk tools should be paired with a formal determination of thrombosis risk, as their results may be most influential for patients at the lower end of thrombosis risk, as well as for highlighting potentially modifiable risk factors for bleeding. Use of bleeding risk scores may assist clinicians and patients in making informed and individualized anticoagulation decisions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Concepts in anticoagulant therapy - past, present, and future].

PubMed

Graf, L

2012-11-01

The understanding of the clotting system emerged in parallel to the development of anticoagulants. In contrast to vitamin K-antagonists and heparins that where discovered by chance, new anticoagulants have been systematically designed to specifically inhibit single clotting factors. Both clotting factors Xa (FXa) and thrombin play a crucial role within the new cell-based model of hemostasis. Thus it is obvious that FXa and thrombin turned out to be ideal targets for anticoagulation. The proof of the concept of selective inhibition of thrombin and FXa has been provided by hirudin and fondaparinux, respectively. By now, a whole group of new oral anticoagulants has been licensed: the direct FXa-inhibitors rivaroxaban, apixaban, and edoxaban as well as the direct thrombin dabigatran etexilate. Furthermore, a bundle of FXa- and thrombin-inhibitors that differ from the so far licensed products mainly in pharmacokinetics are in an advanced phase of development. A further innovative concept of anticoagulation that entered its clinical phase of development is the inhibition of factor VIII. Other new concepts such as inhibition of initiation of coagulation by blocking factor VIIa, inhibition of contact factor XII, or inhibition of factor IX are in an early phase of development.

Risk of gastrointestinal bleeding during anticoagulant treatment.

PubMed

Lanas-Gimeno, Aitor; Lanas, Angel

2017-06-01

Gastrointestinal bleeding (GIB) is a major problem in patients on oral anticoagulation therapy. This issue has become even more pressing since the introduction of direct oral anticoagulants (DOACs) in 2009. Areas covered: Here we review current evidence related to GIB associated with oral anticoagulants, focusing on randomized controlled trials, meta-analyses, and post-marketing observational studies. Dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily increase the risk of GIB compared to warfarin. The risk increase with edoxaban is dose-dependent, while apixaban shows apparently, no increased risk. We summarize what is known about GIB risk factors for individual anticoagulants, the location of GIB in patients taking these compounds, and prevention strategies that lower the risk of GIB. Expert opinion: Recently there has been an important shift in the clinical presentation of GIB. Specifically, upper GIB has decreased with the decreased incidence of peptic ulcers due to the broad use of proton pump inhibitors and the decreased prevalence of H. pylori infections. In contrast, the incidence of lower GIB has increased, due in part to colonic diverticular bleeding and angiodysplasia in the elderly. In this population, the addition of oral anticoagulation therapy, especially DOACs, seems to increase the risk of lower GIB.

Acute Pulmonary Embolism in Emergency Department Patients Despite Therapeutic Anticoagulation.

PubMed

Liu, Michelle Y; Ballard, Dustin W; Huang, Jie; Rauchwerger, Adina S; Reed, Mary E; Bouvet, Sean C; Vinson, David R

2018-05-01

Emergency department (ED) patients with acute pulmonary embolism (PE) despite therapeutic anticoagulation at the time of diagnosis are uncommonly encountered and present a diagnostic and management challenge. Their characterization and outcomes are poorly described. We sought to describe the prevalence and characteristics of therapeutically anticoagulated patients among a population of patients with acute PE in a community setting and to describe treatment changes and 30-day outcomes. From a large retrospective cohort of adults with acute, objectively-confirmed PE across 21 EDs between 01/2013 and 04/2015, we identified patients who arrived on direct oral or injectable anticoagulants, or warfarin with an initial ED international normalized ratio (INR) value ≥2.0. Patients were excluded from the larger cohort if they had received a diagnosis of venous thromboembolism (VTE) in the prior 30 days. We gathered demographic and clinical variables from electronic health records and structured manual chart review. We report discharge anticoagulation regimens and major 30-day adverse outcomes. Among 2,996 PE patients, 36 (1.2%) met study criteria. Mean age was 63 years. Eleven patients (31%) had active cancer and 25 (69%) were high risk on the PE Severity Index (Classes III-V), comparable to the larger cohort (p>0.1). Reasons for pre-arrival anticoagulation were VTE treatment or prevention (n=21), and atrial fibrillation or flutter (n=15). All patients arrived on warfarin and one was also on enoxaparin: 32 had a therapeutic INR (2.0-3.0) and four had a supratherapeutic INR (>3.0). Fifteen patients (42%) had at least one subtherapeutic INR (<2.0) in the 14 days preceding their diagnostic visit. Two patients died during hospitalization. Of the 34 ultimately discharged, 22 underwent a change in anticoagulation drug or dosing, 19 of whom received injectables, either to replace or to supplement warfarin. Four patients also received inferior vena cava filters. Thirty-day outcomes included one major hemorrhage and one additional death. No patients experienced recurrent or worsening VTE. We found a low prevalence of therapeutic anticoagulation at the time of acute PE diagnosis. Most patients with breakthrough PE underwent a change in therapy, though management varied widely. Subtherapeutic anticoagulation levels in the preceding weeks were common and support the importance of anticoagulation adherence.

Acute Pulmonary Embolism in Emergency Department Patients Despite Therapeutic Anticoagulation

PubMed Central

Liu, Michelle Y.; Ballard, Dustin W.; Huang, Jie; Rauchwerger, Adina S.; Reed, Mary E.; Bouvet, Sean C.

2018-01-01

Introduction Emergency department (ED) patients with acute pulmonary embolism (PE) despite therapeutic anticoagulation at the time of diagnosis are uncommonly encountered and present a diagnostic and management challenge. Their characterization and outcomes are poorly described. We sought to describe the prevalence and characteristics of therapeutically anticoagulated patients among a population of patients with acute PE in a community setting and to describe treatment changes and 30-day outcomes. Methods From a large retrospective cohort of adults with acute, objectively-confirmed PE across 21 EDs between 01/2013 and 04/2015, we identified patients who arrived on direct oral or injectable anticoagulants, or warfarin with an initial ED international normalized ratio (INR) value ≥2.0. Patients were excluded from the larger cohort if they had received a diagnosis of venous thromboembolism (VTE) in the prior 30 days. We gathered demographic and clinical variables from electronic health records and structured manual chart review. We report discharge anticoagulation regimens and major 30-day adverse outcomes. Results Among 2,996 PE patients, 36 (1.2%) met study criteria. Mean age was 63 years. Eleven patients (31%) had active cancer and 25 (69%) were high risk on the PE Severity Index (Classes III–V), comparable to the larger cohort (p>0.1). Reasons for pre-arrival anticoagulation were VTE treatment or prevention (n=21), and atrial fibrillation or flutter (n=15). All patients arrived on warfarin and one was also on enoxaparin: 32 had a therapeutic INR (2.0–3.0) and four had a supratherapeutic INR (>3.0). Fifteen patients (42%) had at least one subtherapeutic INR (<2.0) in the 14 days preceding their diagnostic visit. Two patients died during hospitalization. Of the 34 ultimately discharged, 22 underwent a change in anticoagulation drug or dosing, 19 of whom received injectables, either to replace or to supplement warfarin. Four patients also received inferior vena cava filters. Thirty-day outcomes included one major hemorrhage and one additional death. No patients experienced recurrent or worsening VTE. Conclusion We found a low prevalence of therapeutic anticoagulation at the time of acute PE diagnosis. Most patients with breakthrough PE underwent a change in therapy, though management varied widely. Subtherapeutic anticoagulation levels in the preceding weeks were common and support the importance of anticoagulation adherence. PMID:29760849

Stroke prophylaxis in atrial fibrillation: searching for management improvement opportunities in the emergency department: the HERMES-AF study.

PubMed

Coll-Vinent, Blanca; Martín, Alfonso; Malagón, Francisco; Suero, Coral; Sánchez, Juan; Varona, Mercedes; Cancio, Manuel; Sánchez, Susana; Montull, Eugeni; Del Arco, Carmen

2015-01-01

We determine the prevalence of stroke prophylaxis prescription in emergency department (ED) patients with atrial fibrillation and the factors associated with a lack of prescription of anticoagulation in high-risk patients without contraindications. This was a multicenter, observational, cross-sectional study with prospective standardized data collection carried out in 124 Spanish EDs. Clinical variables, risk factors for stroke, type of prophylaxis prescribed, and reasons for not prescribing anticoagulation in high-risk patients (congestive heart failure/left ventricular dysfunction, hypertension, age >75 years, diabetes and previous stroke/transient ischemic attack/systemic embolism [CHADS2] score ≥2 and the congestive heart failure/left ventricular dysfunction, hypertension, age >75 years, diabetes, previous stroke/transient ischemic attack/systemic embolism, vascular disease age 65 to 74 years and sex category [CHA2DS2-VASc] score ≥2) without contraindications were collected. Of 3,276 patients enrolled, 71.5% were at high risk according to CHADS2; 89.7% according to CHA2DS2-VASc. At discharge from the ED, 2,255 patients (68.8%) were receiving anticoagulants, 1,691 of whom (75%) were high-risk patients. Of the 1,931 patients discharged home, anticoagulation was prescribed for 384 patients (19.9%) de novo and for 932 patients (48.3%) previously receiving anticoagulation. The main reasons for not prescribing anticoagulation to eligible patients were considering antiplatelet therapy as adequate prophylaxis (33.1%), advanced age (15%), and considering stroke risk as low (8.3%). Advanced age (odds ratio 0.46; 95% confidence interval 0.30 to 0.69) and female sex (odds ratio 0.50; 95% confidence interval 0.36 to 0.71) were significantly associated with the lack of prescription of anticoagulation to eligible patients. In Spain, most patients with atrial fibrillation treated in EDs who do not receive anticoagulation are at high risk of stroke, with relevant differences with regard to the risk stratification scheme used. Anticoagulation is underused, mainly because the risk of stroke is underestimated by the treating physicians and the benefits of antiplatelets are overrated, principally in female patients and the elderly. Efforts to increase the prescription of anticoagulation in these patients appear warranted. Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Effects of sodium citrate and acid citrate dextrose solutions on cell counts and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel.

PubMed

Giraldo, Carlos E; Álvarez, María E; Carmona, Jorge U

2015-03-14

There is a lack information on the effects of the most commonly used anticoagulants for equine platelet rich plasmas (PRPs) elaboration on cell counts and growth factor release from platelet rich gels (PRGs). The aims of this study were 1) to compare the effects of the anticoagulants sodium citrate (SC), acid citrate dextrose solution A (ACD-A) and ACD-B on platelet (PLT), leukocyte (WBC) and on some parameters associated to platelet activation including mean platelet volume (MPV) and platelet distribution width (PDW) between whole blood, pure PRP (P-PRP) and platelet-poor plasma (PPP); 2) to compare transforming growth factor beta 1 (TGF-β(1)) and platelet-derived growth factor isoform BB (PDGF-BB) concentrations in supernatants from pure PRG (P-PRG), platelet-poor gel (PPG), P-PRP lysate (positive control) and plasma (negative control); 3) to establish the possible correlations between all the studied cellular and molecular parameters. In all cases the three anticoagulants produced P-PRPs with significantly higher PLT counts compared with whole blood and PPP. The concentrations of WBCs were similar between P-PRP and whole blood, but significantly lower in PPP. The type of anticoagulant did not significantly affect the cell counts for each blood component. The anticoagulants also did not affect the MPV and PDW parameters. Independently of the anticoagulant used, all blood components presented significantly different concentrations of PDGF-BB and TGF-β(1). The highest growth factor (GF) concentrations were observed from P-PRP lysates, followed by PRG supernatants, PPP lysates, PPG supernatants and plasma. Significant correlations were observed between PLT and WBC counts (ρ = 0.80), PLT count and TGF-β(1) concentration (ρ = 0.85), PLT count and PDGF-BB concentration (ρ = 0.80) and PDGF-BB and TGF-β(1) concentrations (ρ = 0.75). The type of anticoagulant was not correlated with any of the variables evaluated. The anticoagulants did not significantly influence cell counts or GF concentrations in equine PRP. However, ACD-B was apparently the worst anticoagulant evaluated. It is necessary to perform additional research to determine the effect of anticoagulants on the kinetics of GF elution from P-PRG.

Photographic fixative poisoning

MedlinePlus

Photographic developer poisoning; Hydroquinone poisoning; Quinone poisoning; Sulfite poisoning ... Poisonous ingredients include: Hydroquinones Quinones Sodium ... fixative can also break down (decompose) to form sulfur dioxide ...

[Pidemiological analysis of pesticide poisoning in hangzhou during 2006-2013].

PubMed

Zhang, Lei; Hao, Li; Zhang, Xuhui; Chen, Jianchun; Wang, Qiang; Yu, Long

2015-01-01

The purpose of this current investigation was to describe the distribution characteristics of pesticides poisoning in Hangzhou during 2006-2013. The registration data of pesticide poisoning in Hangzhou during 2006-2013 were collected from health disserve surveillance information system which was part of China information system for disease control and prevention. The statistical analysis method included Pearson Chi-square test and Cochran-Armitage trend test. There were totally 6232 cases with pesticide poisoning during 2006-2013, of which 414 cases died. The fatality rate of poisoning patients was 6.64%. The pesticides, especially organophosphorus pesticides, were the main poison that caused poisoning, and patients with pesticide poisoning accounted for 80.60% of all the poisoning patient. There was more female patients than male patients among non-productive pesticide poisoning, but on the contrary among productive pesticide poisoning. The incidence of pesticides poisoning had significant increase in the third season. Occupational pesticide poisoning and non-occupational pesticide poisoning had the different distribution character. Non-occupational pesticide poisoning was the chief reason of pesticide poisoning. The pesticides, especially organophosphorus pesticides, were the main poisons threatening the health of people in Hangzhou, and the effective prevention and control measures should be taken immediately.

Evaluating the impact of new anticoagulants in the hospital setting

PubMed Central

Braidy, Nady; Bui, Khai; Bajorek, Beata

2010-01-01

The short-comings of current anticoagulants have led to the development of newer, albeit more expensive, oral alternatives. Objective To explore the potential impact the new anticoagulants dabigatran and rivaroxaban in the local hospital setting, in terms of utilisation and subsequent costing. Method A preliminary costing analysis was performed based on a prospective 2-week clinical audit (29th June - 13th July 2009). Data regarding current anticoagulation management were extracted from the medical files of patients admitted to Ryde Hospital. To model potential costing implications of using the newer agents, the reported incidence of VTE/stroke and bleeding events were obtained from key clinical trials. Results Data were collected for 67 patients treated with either warfarin (n=46) or enoxaparin (n=21) for prophylaxis of VTE/stroke. At least two-thirds of all patients were deemed suitable candidates for the use of newer oral anticoagulants (by current therapy: warfarin: 65.2% (AF), 34.8% (VTE); enoxaparin: 100%, (VTE)). The use of dabigatran in VTE/stroke prevention was found to be more cost- effective than warfarin and enoxaparin due to significantly lower costs of therapeutic monitoring and reduced administration costs. Rivaroxaban was more cost-effective than warfarin and enoxaparin for VTE/stroke prevention when supplier-rebates (33%) were factored into costing. Conclusion This study highlights the potential cost- effectiveness of newer anticoagulants, dabigatran and rivaroxaban, compared to warfarin and enoxaparin. These agents may offer economic advantages, as well as clinical benefits, in the hospital-based management of anticoagulated patients. PMID:25132883

Monitoring therapeutic anticoagulation with low molecular weight heparins: is it useful or misleading?

PubMed

Hammerstingl, C

2008-10-01

Weight adapted low molecular weight heparin (LMWH) treatment is recommended as initial anticoagulant therapy of deep vein thrombosis, pulmonary embolism, in patients with myocardial ischemia or when oral anticoagulation (OAC) must be interrupted peri- operatively. Traditionally unfractioned heparin (UFH) was used as standard short acting anticoagulant, with the therapy monitored by frequent laboratory testing. Currently LMWH have broadly replaced UFH as first- choice anticoagulant due to more preferable pharmacokinetics and a better safety profile. Therapeutic anticoagulation with LMWH can be achieved by subcutaneous weight adapted application and measurement of anti-factor Xa- activity (anti-Xa) has been established as gold standard for LMWH- monitoring. However, since almost all LMWH dosing regimens have been developed empirically without laboratory monitoring, there is still a debate ongoing about the usefulness and impact of anti-Xa-testing. Data are lacking that prove a clear correlation between obtained levels of anti-Xa and the patients' clinical outcome. Newer methods have been developed aiming to determine a broader spectrum of LMWH depending anticoagulant activity. Even though there are some promising preliminary results, these alternative methods are not ready for routine clinical use yet. Nevertheless, current guidelines advise determination of anti-Xa in special patient populations with markedly altered LMWH metabolism or to exclude residual LMWH- activity before surgery at very high risk of bleeding. The aim of this article is to review critically the usefulness of anti- Xa guidance of LMWH- therapy and to give new perspectives on upcoming methods of LMWH- monitoring.

Stroke prevention with oral anticoagulation in older people with atrial fibrillation - a pragmatic approach.

PubMed

Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

2012-08-01

With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians' fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients' views.

Stroke Prevention with Oral Anticoagulation in Older People with Atrial Fibrillation - A Pragmatic Approach

PubMed Central

Ali, Ali; Bailey, Claire; Abdelhafiz, Ahmed H

2012-01-01

With advancing age, the prevalence of both stroke and non valvular atrial fibrillation (NVAF) is increasing. NVAF in old age has a high embolic potential if not anticoagulated. Oral anticoagulation therapy is cost effective in older people with NVAF due to their high base line stroke risk. The current stroke and bleeding risk scoring schemes have been based on complex scoring systems that are difficult to apply in clinical practice. Both scoring schemes include similar risk factors for ischemic and bleeding events which may lead to confusion in clinical decision making to balance the risks of bleeding against the risks of stroke, thereby limiting the applicability of such schemes. The difficulty in application of such schemes combined with physicians’ fear of inducing bleeding complications has resulted in under use of anticoagulation therapy in older people. As older people (≥75 years) with NVAF are all at high risk of stroke, we are suggesting a pragmatic approach based on a yes/no decision rather than a risk scoring stratification which involves an opt out rather an opt in approach unless there is a contraindication for oral anticoagulation. Antiplatelet agents should not be an alternative option for antithrombotic treatment in older people with NVAF due to lack of efficacy and the potential of being used as an excuse of not prescribing anticoagulation. Bleeding risk should be assessed on individual basis and the decision to anticoagulate should include patients’ views. PMID:23185715

Simple and rapid assay for effect of the new oral anticoagulant (NOAC) rivaroxaban: preliminary results support further tests with all NOACs

PubMed Central

2014-01-01

Background New oral anticoagulant (NOAC) drugs are known to influence the results of some routine hemostasis tests. Further data are needed to enable routine assessment of the effects of NOAC on clotting parameters in some special circumstances. Methods Following administration of rivaroxaban to patients, at the likely peak and trough activity times, we assessed the effects on prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and clotting time using Russell’s viper venom, and in the presence of phospholipids and calcium reagent available as DVVreagent® and DVVconfirm®. The data were used to determine an adequate NOAC plasma level based on anticoagulant activities expressed as a ratio (patients/normal, R-C). Results DVVconfirm as R-C could be rapidly performed, and the results were reasonably sensitive for rivaroxaban and probably for other FX inhibitors. This assay is not influenced by lupus anticoagulant and heparin, does not require purified NOAC as control, and will measure whole-plasma clotting activity. Conclusions We propose a cut-off R-C value of 4.52 ± 0.33 for safety, but clinical studies are needed to establish whether this cut-off is useful for identifying patients at increased risk of hemorrhage or exhibiting low anticoagulation effect. It also seems possible that normal R-C could indicate an absence of anticoagulant activity when rivaroxaban is discontinued due to episodes of uncontrolled bleeding during anticoagulation or for emergency surgery. PMID:24656069

Carbolic acid poisoning

MedlinePlus

Phenol poisoning; Phenylic acid poisoning; Hydroxybenzene poisoning; Phenic acid poisoning; Benzenol poisoning ... measure and monitor the person's vital signs, including temperature, pulse, breathing rate, and blood pressure. Tests that ...

[Analysis of the characteristics of toxins in 6005 cases of acute poisoning in Guangxi].

PubMed

Jiang, Dong-fang; Zhang, Zhen-ming; Hu, De-hong; Liu, Qing-hua

2013-07-01

To investigate the toxin characteristics of toxins in patients of acute poisoning in the Guangxi area. A retrospective study was conducted. The data of acute poisoning cases and the causative toxins collected from 63 hospitals of Guangxi, including 36 city hospitals, 12 county hospitals, and 15 township health centers from January 2005 to December 2009 were collected. The data were descriptively analyzed and classified by year. A total of 6005 cases with acute poisoning induced by 532 kinds of poisons were enrolled. The 532 kinds of toxin were classified by high-occurrence (producing poisoning for 5 continuous years), low-occurrence (leading to poisoning for 2-4 continuous years) and newly occurred categories (leading to poisoning only in 1 year). The numbers of poisons of these 3 categories accounted for 10.15% (54 kinds), 29.70% (158 kinds), 60.15% (320 kinds) of total number of poisons, respectively. There were 4688 (78.07%), 780 (12.99%), and 537 (8.94%) cases for each category respectively. And the poisoning cases of each toxin involved from 8 to 837, 2 to 25, and 1 to 69 cases respectively. 77.78% (42/54) of high-occurrence poisons affect more than 20 cases, and 89.87% (142/158), 98.75% (316/320) of low-occurrence and new-occurrence poisons involved less than 10 cases. In the dynamic analyses for 5 years, frequency of toxin caused by high-occurrence, low-occurrence and newly occurred poisons in 5 years were 5 times, 2.6 times, and 1 time, respectively. The number of poisons caused by the high-occurrence toxin each year were same, but the average-annual growth rates of poison numbers caused by the low-occurrence and new-occurrence poisons each year were 17.61% and 20.10%. The average-annual growth rates of poisoning cases caused by the 3 categories of poisons were 14.08%, 16.53%, 31.96%, and the average-annual growth rates of poisoning cases caused by each categories were 10.28%, 1.13%, 11.45%, respectively. In the high-occurrence category, the poison species was least, the poisoning cases were most, the variety of the affected cases by each poison was largest, and the case involved by each toxin was increased by year. But in the newly occurred category, the poison constituent ratio was largest, but the poisoning population was the least, the disparity of each poison was least, and the toxin increased and the population affected each year were elevated. The characteristics of low-occurrence poison were between high-occurrence poison and newly occurred poison.

Design of anticoagulant surfaces based on cellulose nanocrystals.

PubMed

Ehmann, Heike M A; Mohan, Tamilselvan; Koshanskaya, Maria; Scheicher, Sylvia; Breitwieser, Doris; Ribitsch, Volker; Stana-Kleinschek, Karin; Spirk, Stefan

2014-11-07

The anticoagulant activity of surfaces decorated with cellulose nanocrystals (CNCs) prepared via sulfuric acid hydrolysis, is explored. Such surfaces bear a high amount of negatively charged sulfate groups, which mimic the naturally occurring anticoagulant heparin in terms of charge density. It is demonstrated that CNC decorated surfaces significantly enhance the coagulation times of blood plasma and whole blood as proven by QCM-D and simple clotting tests.

Efficacy and safety of a pharmacist-managed inpatient anticoagulation service for warfarin initiation and titration.

PubMed

Wong, Y M; Quek, Y-N; Tay, J C; Chadachan, V; Lee, H K

2011-10-01

Anticoagulation consultations provided by a pharmacist-staffed inpatient service, similar to the experience reported in outpatient anticoagulation clinics, can potentially improve anticoagulation control and outcomes. At Tan Tock Seng Hospital, a 1200-bed acute care teaching hospital in Singapore, pharmacist-managed anticoagulation clinics have been in place since 1997. Pharmacist-managed services were extended to inpatient consultations in anticoagulation management from April 2006. Our objective was to assess the effect of implementing a pharmacist-managed inpatient anticoagulation service. This was a single-centre cohort study. Baseline data from 1 January 2006 to 31 March 2006 were collected and compared with post-implementation data from 1 April 2006 to 31 March 2007. Patients newly started on warfarin for deep vein thrombosis, pulmonary embolism or atrial fibrillation in general medicine and surgery departments were included. The three endpoints were as follows: (i) percentage of international normalized ratios (INRs) achieving therapeutic range within 5 days, (ii) INRs more than 4 during titration and (iii) subtherapeutic INRs on discharge. A total of 26 patients in the control period were compared with 144 patients who had received dosing consultations by a pharmacist during the initiation of warfarin. The provision of pharmacist consult resulted in 88% compared to 38% (P < 0·001) of INR values achieving therapeutic range within 5 days. There was a reduction in INR values of more than 4 during titration from 27% to 2% (P < 0·001), and subtherapeutic INR values on discharge without low molecular weight heparin from 15% to 0% (P < 0·001). The mean time to therapeutic INR was reduced from 6·5 to 3·9 days (P < 0·001) and mean length of stay after initiation of warfarin from 11 to 7·7 days (P = 0·004). Inpatient anticoagulation care and outcomes were significantly improved by a pharmacist-managed anticoagulation service. The time to therapeutic INR was achieved appropriately and efficiently without compromising patient's safety. © 2010 The Authors. JCPT © 2010 Blackwell Publishing Ltd.

Efficacy and Safety of Oral Anticoagulants Versus Aspirin for Patients With Atrial Fibrillation

PubMed Central

Zhang, Jing-Tao; Chen, Ke-Ping; Zhang, Shu

2015-01-01

Abstract The purpose of this study was to perform a meta-analysis comparing the effectiveness and safety of anticoagulation to antiplatelet therapy for the prevention of thromboembolic events in patients with atrial fibrillation (AF). MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched for studies published through May 31, 2014. Randomized controlled trials comparing anticoagulants (warfarin) and antiplatelet therapy in patients with AF were included. The primary outcomes were the rates of stroke and systemic embolism. Secondary outcomes included the rates of hemorrhage/major bleeding and death. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Nine reports of 8 trials that enrolled 4363 patients (2169 patients received anticoagulation and 2194 antiplatelet therapy) were included. All of the studies compared adjusted-dose warfarin or with aspirin, and the majority of the patients were >70 years of age. Anticoagulants were titrated to an international normalized ratio (INR) of 2.0 to 4.5, and aspirin was administered at a dosage of 75 to 325 mg/d. Death occurred in 206 participants treated with an anticoagulant and 229 participants treated with antiplatelet therapy. There was no significant difference in the overall stroke rate between the groups (OR = 0.667, 95% CI 0.426–1.045, P = 0.08); however, patients with nonrheumatic AF (NRAF) treated with an anticoagulant had a lower risk of stroke (OR = 0.557, 95% CI 0.411–0.753, P < 0.001). Anticoagulants were associated with a lower risk of embolism (OR = 0.616, 95% CI = 0.392–0.966, P = 0.04), and this finding persisted in patients with NRAF (OR = 0.581, 95% CI 0.359–0.941, P = 0.03). No significant difference in the rate of hemorrhage/major bleeding was noted (OR = 1.497, 95% CI 0.730–3.070, P = 0.27), and this finding persisted on subgroup analysis. Anticoagulants appear to be more effective than aspirin in preventing embolisms in patients with AF, as the risk of bleeding is not increased. PMID:25634169

Practical considerations in emergency management of bleeding in the setting of target-specific oral anticoagulants.

PubMed

Miller, Michael P; Trujillo, Toby C; Nordenholz, Kristen E

2014-04-01

The recent arrival of the target-specific oral anticoagulants (TSOACs) offers potential advantages in the field of anticoagulation. However, there are no rapid and accurate and routinely available laboratory assays to evaluate their contribution to clinical bleeding. With the expanding clinical indications for the TSOACs, and the arrival of newer reversal agents on the market, the emergency clinician will need to be familiar with drug specifics as well as methods for anticoagulation reversal. This review offers a summary of the literature and some practical strategies for the approach to the patient taking TSOACs and the management of bleeding in these cases. Copyright © 2014 Elsevier Inc. All rights reserved.

Bleeding events associated with novel anticoagulants: a case series.

PubMed

Mirzaee, Sam; Tran, Tara Thi Thien; Amerena, John

2013-12-01

Until lately warfarin was the only valuable oral anticoagulant in stroke reduction in high risk cases with non valvular atrial fibrillation (NVAF). Although with warfarin the rate of stroke reduced notably, the major concern is the risk of serious bleeding and difficulty of establishing and maintaining the international normalised ratio (INR) within the therapeutic range. With the development of the novel anticoagulants we now have for the first time since the innovation of Warfarin feasible alternatives to it to decrease stroke rates in high risk patients with NVAF. To diminish adverse bleeding events with the novel anticoagulant proper selection of patients prior starting treatment is essential. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

PubMed

Ruff, Christian T; Giugliano, Robert P; Braunwald, Eugene; Hoffman, Elaine B; Deenadayalu, Naveen; Ezekowitz, Michael D; Camm, A John; Weitz, Jeffrey I; Lewis, Basil S; Parkhomenko, Alexander; Yamashita, Takeshi; Antman, Elliott M

2014-03-15

Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045). This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

Environmental and Water Quality Operational Studies. Environmental Features for Streamside Levee Projects.

DTIC Science & Technology

1985-08-01

Lyon 1976, Lyon and Basile 1979, Lyon and Jenson 1980) showed that windrows over 1.5 ft tall are avoided by mule deer and elk. Thus, brush piles...various State pesticide control authorities. Label directions and general regulations promulgated by these agencies have the power of law and should be...matters, relative attractiveness of alternative baits can vary with season. 606. Like other pesticides , rodenticides are strictly controlled 0 by

EMERGING INFECTIOUS DISEASES. Actions Needed to Address the Challenges of Responding to Zika Virus Disease Outbreaks

DTIC Science & Technology

2017-05-01

Department of Health and Human Services 81 Appendix IV Zika Virus Case Definitions for National Notifiable Disease Reporting 86 Appendix V...Insecticide, Fungicide, and Rodenticide Act HHS Department of Health and Human Services IgG immunoglobulin G IgM immunoglobulin M IMM...Agency (EPA), and Department of Health and Human Services (HHS) including CDC, FDA and National Institutes of Health (NIH). We also convened, with

[Analysis of 4713 cases of Wuhan pesticide poisoning reports of year 2002 to 2010].

PubMed

Chen, Zhen-long; Li, Song-han; Wang, Ying; Yu, Li; Yi, Gui-lin; Yan, Yan-ling

2011-10-01

To provide scientific evidence of making measures for prevention of pesticide poisoning, the investigation on the condition of pesticides poisoning was carried out in Wuhan. Registration data of pesticide poisoning from 2002 to 2010 in Wuhan were collected and statistically analyzed by SAS 9.1. During the nine years, there were 4713 cases reported for pesticide poisoning. Among them, the number of occupational poisoning was 2737 (2 cases died), with fatality rate of 0.07%. The number of non-occupational poisoning was 1976 (159 cases died), and its fatality rate was 8.05%. The incidence of occupational poisoning and non-occupational poisoning accounted for 58.1% and 41.9%, respectively. Insecticides especially organophosphorus insecticides, such as parathion, dichlorvos, and methamidophos accounted for 70.6% of the poisoning. Occupational poisoning took place mainly in man, accounting for 68.8%, Non-occupational or life poisoning in contrast mainly occurred in women with a proportion of 66.8%. The majority of the occupational poisoning were 30-59 year-old patients (2239 cases, 81.8%). The majority of the non-occupational poisoning were 30-44 year-old patients (665 cases, 33.6%) and - 70 years old patients (209 cases, 10.6%). High incidence of occupational pesticide poisoning, the regional distribution of Caidian (1016 cases, 37.1% ) highest, followed by the Dongxihu, Hannan and Huangpi. The pesticide poisoning mainly occurred from July to September. The occupational poisoning was mainly caused by poor protection, long working hours, and practice not implemented. The non-occupational poisoning was mainly caused by suicide. The majority of the occupational poisoning in Wuhan was middle-aged men. The pesticide poisoning was main caused by insecticides.

Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass.

PubMed

Gunaratne, Ruwan; Kumar, Shekhar; Frederiksen, James W; Stayrook, Steven; Lohrmann, Jens L; Perry, Kay; Bompiani, Kristin M; Chabata, Charlene V; Thalji, Nabil K; Ho, Michelle D; Arepally, Gowthami; Camire, Rodney M; Krishnaswamy, Sriram; Sullenger, Bruce A

2018-06-04

Unfractionated heparin (UFH), the standard anticoagulant for cardiopulmonary bypass (CPB) surgery, carries a risk of post-operative bleeding and is potentially harmful in patients with heparin-induced thrombocytopenia-associated antibodies. To improve the activity of an alternative anticoagulant, the RNA aptamer 11F7t, we solved X-ray crystal structures of the aptamer bound to factor Xa (FXa). The finding that 11F7t did not bind the catalytic site suggested that it could complement small-molecule FXa inhibitors. We demonstrate that combinations of 11F7t and catalytic-site FXa inhibitors enhance anticoagulation in purified reaction mixtures and plasma. Aptamer-drug combinations prevented clot formation as effectively as UFH in human blood circulated in an extracorporeal oxygenator circuit that mimicked CPB, while avoiding side effects of UFH. An antidote could promptly neutralize the anticoagulant effects of both FXa inhibitors. Our results suggest that drugs and aptamers with shared targets can be combined to exert more specific and potent effects than either agent alone.