Radiological findings in poisoning by synthetic cannabinoids adulterated with brodifacoum.

OBJECTIVES: Severe coagulopathy due to consumption of synthetic cannabinoids adulterated with brodifacoum, a long-acting anticoagulant, is an emerging worldwide hazard. Here, we review the spectrum of imaging findings in adulterated cannabinoid poisoning. MATERIALS AND METHODS: In this retrospective study, we used the Israeli Poison Information Center database to identify patients with cannabinoid-associated coagulopathy who presented to the Rambam Health Care Campus, where most patients were treated during an outbreak in northern Israel between September 2021 and June 2022. All relevant imaging studies for these patients were reviewed. We estimated the sensitivity of findings for cannabinoid-associated coagulopathy. Associations between a continuous variable and a dichotomous outcome were assessed with the Mann-Whitney U test. RESULTS: We identified 48 patients (mean age 40 years ± 9 [SD], 43 males) with 54 hospitalizations due to cannabinoid-associated coagulopathy. Symptomatic hemorrhage was documented in 50 (93%) cases at presentation, most of whom (78%) had hemorrhage from multiple systems. The most common bleeding site was the genitourinary collecting system, with a characteristic sign of suburothelial bleeding in 16/18 of performed abdominal CTs (sensitivity 89% [CI 65-99%] for cannabinoid-associated coagulopathy). Intramural bowel hematomas were noted in 70% (7/10) of CTs of patients with gastrointestinal bleeding. Incidental bleeding sites were identified on imaging in 24% of patients. An increased number of bleeding sites was associated with need for vasopressors (difference in bleeding sites 3.00 [95% CI 0.99-4.00], p = 0.026). CONCLUSION: CT plays a key role in the diagnosis and work-up of adulterated cannabinoid-associated coagulopathy. Characteristic signs include suburothelial hemorrhage and intramural bowel hematomas. CLINICAL RELEVANCE STATEMENT: Recognition of radiological signs of adulterated synthetic cannabinoid-associated coagulopathy is critical for optimizing outbreak control on the public health level and ensuring timely treatment on the individual patient level. KEY POINTS: • Severe coagulopathy due to consumption of synthetic cannabinoids adulterated with brodifacoum, a long-acting anticoagulant, is an emerging worldwide threat. • Characteristic imaging signs include suburothelial bleeding, intramural bowel hematomas, and rare incidental bleeding sites. • Imaging has a pivotal role in optimizing outbreak control and ensuring timely and appropriate treatment.

Anticoagulant rodenticide toxicity in dogs: A retrospective study of 349 confirmed cases in Saskatchewan.

Objective: To evaluate the signalment and clinical, laboratory, treatment, and outcome features of dogs diagnosed with anticoagulant rodenticide (AR) intoxication in Saskatchewan. Animals: We studied 349 dogs. Procedure: Medical records from the Veterinary Medical Centre (Saskatoon, Saskatchewan) between 1999 and 2022 were reviewed. Cases were included if they met at least 1 of the following criteria: owner witnessed the dog ingesting an AR; AR was seen in the vomitus when emesis was induced; the dog had clinical signs of coagulopathy, with elevation of PT ± aPTT that normalized after vitamin K1 therapy, in the presence of appropriate clinical and paraclinical data and the absence of other causes of hypocoagulable state determined by the primary clinician. Results: Fifty-three percent of cases were seen between July and October. Most dogs (61%) came from an urban setting. Ninety-two percent of dogs ingested a 2nd-generation AR and the most frequent toxin was bromadiolone. Clinical signs were reported in 30% of AR intoxications and included lethargy (86%), dyspnea (55%), and evidence of external hemorrhage (44%). The most common site of hemorrhage was the pleural space, accounting for 43% of hemorrhage sites. Consumptive thrombocytopenia was reported in 24% of dogs with evidence of AR-induced hemorrhage, with moderate (platelet count < 60 K/µL) and marked (< 30 K/µL) thrombocytopenia in 7/12 and 2/12 dogs, respectively. Blood products were administered to 84% of dogs with AR-induced hemorrhage; the most common product administered was fresh frozen plasma (56% of cases). Among dogs with AR-induced hemorrhage, those that received blood products were more likely to survive to discharge (81%) compared to those that did not (19%) (P = 0.017). Eighty-six percent of dogs with AR-induced hemorrhage survived to discharge. Conclusion and clinical relevance: The pleural space was the most common site of hemorrhage. Moderate thrombocytopenia was a common finding. Eighty-six percent of dogs with AR-induced hemorrhage survived to discharge.

Toxicité des rodenticides anticoagulants chez les chiens : étude rétrospective de 349 cas confirmés en Saskatchewan. Objectif: Évaluer le signalement et les caractéristiques cliniques, de laboratoire, de traitement et de résultats des chiens diagnostiqués avec une intoxication par un rodenticide anticoagulant (AR) en Saskatchewan. Animaux: Nous avons étudié 349 chiens. Procédure: Les dossiers médicaux du Veterinary Medical Centre (Saskatoon, Saskatchewan) entre 1999 et 2022 ont été examinés. Les cas ont été inclus s'ils répondaient à au moins 1 des critères suivants : le propriétaire a vu le chien ingérer un AR; de l'AR a été observée dans les vomissures lorsque des vomissements ont été provoqués; le chien présentait des signes cliniques de coagulopathie, avec une élévation du PT ± aPTT qui s'est normalisée après un traitement par la vitamine K1, en présence de données cliniques et paracliniques appropriées et en l'absence d'autres causes d'état hypocoagulable déterminées par le clinicien initial. Résultats: Cinquante-trois pour cent des cas ont été observés entre juillet et octobre. La plupart des chiens (61 %) venaient d'un milieu urbain. Quatre-vingt-douze pour cent des chiens ont ingéré un AR de 2e génération et la toxine la plus fréquente était la bromadiolone. Des signes cliniques ont été rapportés dans 30 % des intoxications par AR et incluaient de la léthargie (86 %), de la dyspnée (55 %) et des signes d'hémorragie externe (44 %). Le site d'hémorragie le plus fréquent était l'espace pleural, représentant 43 % des sites d'hémorragie. Une thrombocytopénie de consommation a été rapportée chez 24 % des chiens présentant des signes d'hémorragie induite par l'AR, avec une thrombocytopénie modérée (nombre de plaquettes < 60 K/µL) et marquée (< 30 K/µL) chez 7 chiens sur 12 et 2 chiens sur 12, respectivement. Des produits sanguins ont été administrés à 84 % des chiens présentant une hémorragie induite par l'AR; le produit le plus fréquemment administré était le plasma frais congelé (56 % des cas). Parmi les chiens présentant une hémorragie induite par l'AR, ceux qui ont reçu des produits sanguins étaient plus susceptibles de survivre jusqu'à leur congé (81 %) que ceux qui n'en ont pas reçu (19 %) (P = 0,017). Quatre-vingt-six pour cent des chiens présentant une hémorragie induite par l'AR ont survécu jusqu'à leur sortie. Conclusion et pertinence clinique: L'espace pleural était le site d'hémorragie le plus fréquent. Une thrombocytopénie modérée était fréquente. Quatre-vingt-six pour cent des chiens présentant une hémorragie induite par l'AR ont survécu jusqu'à leur sortie.(Traduit par Dr Serge Messier).

[Managing Superwarfarin Poisoning: A Challenging Case]. / Relato de caso de intoxicación con superwarfarinas: un desafío terapéutico.

Human intoxication by long-acting anticoagulant rodenticides, known as superwarfarins, causes coagulopathy that is difficult to manage. We present the case of a 42-year-old man who ingested a toxic dose of rodenticide in a suicide attempt, evolving with epistaxis, INR of 11.6, and needing hospitalization. For seven days, serial controls of coagulation tests were carried out, with optimization of different doses of Vitamin K supplementation. The case highlights this type of anticoagulant's potency and prolonged half-life (approximately six weeks), which requires regular clinical control and satisfactory treatment adherence.

Bad weed: synthetic cannabinoid-associated coagulopathy.

Recent multistate outbreaks of coagulopathy caused by brodifacoum-tainted synthetic cannabinoids or "fake weed" highlight the public health impact of long-acting anticoagulant rodenticides (LAARs). Patients presenting with this syndrome have had recent exposure to synthetic cannabinoids, evidence of isolated vitamin K antagonism with or without bleeding, and detectable levels of brodifacoum and other LAARs in circulation. This article will provide information on synthetic cannabinoids, LAARs, and coagulopathic manifestations arising from use of adulterated synthetic cannabinoids and their management.

Time to Peak International Normalized Ratio Rise in Acute and Acute-on-Chronic Warfarin Overdoses.

ABSTRACT: Guidelines exist on the management of supratherapeutic/subtherapeutic international normalized ratio (INR) values for patients on warfarin. However, there is a paucity of the literature relating to an acute overdose of warfarin. This is a retrospective cohort study for all acute and acute-on-chronic (AOC) warfarin overdoses reported to the Maryland Poison Center in patients ≥12 years between January 1st, 2000, until October 31st, 2019, managed in a health care facility. The primary outcome was to determine the time after presentation to peak INR. Secondary outcomes included risk factors associated with INR >10 and describing patient characteristics. A total of 163 overdoses were included, 68 acute and 95 AOC. In patients who did not receive reversal therapies, INR peaked at a median value of 3.8 (interquartile range 2.6-5.5) between 24 and 36 hours. The median time to phytonadione was 22.0 hours. Most patients received phytonadione (62.0%), with fewer receiving blood products (16.6%). The median warfarin dose ingested was 75 mg. The AOC group had a greater mean age (56 vs. 43 years), median INR value (2.4 vs. 1.4), and men (62.1% vs. 41.2%). Factors associated with an INR > 10 included initial INR and reported quantity ingested. Peak INR was greater in the AOC than the acute overdose group (6.1 vs. 3.4), although the bleeding rate was similar. Peak INR values after warfarin overdose occur between 24 and 36 hours after presentation. Initial INRs and reported quantity ingested may be useful to predict those needing treatment.

Accidental apixaban intoxication in a 23-month-old child: a case report.

BACKGROUND: Direct oral anticoagulants, such as apixaban, are increasingly used in everyday practice in order to treat or prevent thromboembolic diseases. To date, there is no available data about apixaban pharmacokinetics in children, and no intoxication has previously been described. CASE PRESENTATION: A 23-month-old boy, with no medical history, was admitted to the emergency department 2 h after accidentally ingesting 40 mg apixaban and 0.75 mg digoxin. No adverse event was observed. Digoxin trough level was within therapeutic values. Apixaban blood concentration increased up to 1712 µg/L at H + 6 (1000-2750 µg/L using 2-5 mg/kg of apixaban in adults). The terminal half-life was 8.2 h (6-15 h in adults). The rapid elimination may explain the absence of bleeding despite high concentrations. CONCLUSIONS: Despite an important intake of apixaban and a real disturbance in routine coagulation assays, no clinical sign of bleeding was observed, perhaps due to wide therapeutic range of apixaban. It may also be explained by its rapid elimination. Considering the high Cmax and a possible enteroenteric recycling, the use of activated charcoal should be considered in such situations in order to prevent eventual bleeding.

Evaluating a Rapid Field Assessment System for Anticoagulant Rodenticide Exposure of Raptors.

Anticoagulant rodenticides (ARs) are commonly used to control rodent pests. However, worldwide, their use is associated with secondary and tertiary poisoning of nontarget species, especially predatory and scavenging birds. No medical device can rapidly test for AR exposure of avian wildlife. Prothrombin time (PT) is a useful biomarker for AR exposure, and multiple commercially available point-of-care (POC) devices measure PT of humans, and domestic and companion mammals. We evaluated the potential of one commercially available POC device, the Coag-Sense® PT/INR Monitoring System, to rapidly detect AR exposure of living birds of prey. The Coag-Sense device delivered repeatable PT measurements on avian blood samples collected from four species of raptors trapped during migration (Intraclass Correlation Coefficient > 0.9; overall intra-sample variation CV: 5.7%). However, PT measurements reported by the Coag-Sense system from 81 ferruginous hawk (Buteo regalis) nestlings were not correlated to those measured by a one-stage laboratory avian PT assay (r = - 0.017, p = 0.88). Although precise, the lack of agreement in PT estimates from the Coag-Sense device and the laboratory assay indicates that this device is not suitable for detecting potential AR exposure of birds of prey. The lack of suitability may be related to the use of a mammalian reagent in the clotting reaction, suggesting that the device may perform better in testing mammalian wildlife.

Exploratory Ingestions of Novel Anticoagulants and Antiplatelets: What Is the Risk?

BACKGROUND: Historically, anticoagulants and antiplatelet agents included warfarin and aspirin, respectively. In recent years, numerous novel anticoagulants (eg, direct thrombin inhibitors and factor Xa inhibitors) as well as the adenosine diphosphate receptor antagonists have increased significantly. Little information on the bleeding risk after exploratory ingestion of these agents is available. The primary purpose of this study is to evaluate the bleeding risk of these agents after an exploratory ingestion in children 6 years or younger. METHODS: This retrospective multicenter poison control center study was conducted on calls between 2005 and 2014. The following agents were included: apixaban, clopidogrel, dabigatran, edoxaban, prasugrel, rivaroxaban, or ticagrelor. Bleeding characteristics and treatment rendered were recorded. RESULTS: A total of 638 cases were identified. Most cases involved antiplatelet agents. No patient developed any bleeding complication. The administration of charcoal was independent of the amount of drug ingested. CONCLUSION: Accidental, exploratory ingestions of these agents seem well tolerated, with no patient developing bleeding complications.

Adherence to Long-Term Follow-Up of Patients with Life-Threatening, Inhaled Synthetic Cannabinoids-Associated Coagulopathy in Chicago.

A large-scale outbreak of life-threatening, inhaled synthetic cannabinoids (Spice/K2)-associated coagulopathy with bleeding complications was recently reported in Illinois. The causative agents were brodifacoum, difenacoum, and bromadiolone, potent, long-acting, 4-hydroxycoumarin anticoagulant rodenticides (LAAR) that were mixed with Spice/K2 products procured and then inhaled by the victims. We report on 3 poisoned patients who reside in underserved, socioeconomically disadvantaged neighborhoods of Chicago that were admitted and treated successfully at two inner-city, tertiary care hospitals in Chicago. The patients were discharged from the hospitals on daily long-term high-dose oral vitamin K1 (VK1), provided free of charge. However, 2 patients were lost to follow-up prior to safe discontinuation of oral VK1 therapy. The third patient was treated and followed successfully for 7 months when VK1 was discontinued. We conclude that prolonged oral VK1 therapy and follow-up of acute, life-threatening LAAR poisoning are variable and present challenges to healthcare providers. Appropriate practice guidelines to improve patient access and adherence to daily high-dose oral VK1 therapy and follow-up should be developed and implemented.

Assessing Bleeding Risk in Patients With Intentional Overdoses of Novel Antiplatelet and Anticoagulant Medications.

STUDY OBJECTIVE: In recent years, the use of novel anticoagulants and antiplatelet agents has become widespread. Little is known about the toxicity and bleeding risk of these agents after acute overdose. The primary objective of this study is to evaluate the relative risk of all bleeding and major bleeding in patients with acute overdose of novel antiplatelet and anticoagulant medications. METHODS: This study is a retrospective study of acute ingestion of apixaban, clopidogrel, ticlopidine, dabigatran, edoxaban, prasugrel, rivaroxaban, and ticagrelor reported to 7 poison control centers in 4 states during a 10-year span. The prevalence of bleeding for each agent was calculated, and hemorrhage was classified as trivial, minor, or major. RESULTS: A total of 322 acute overdoses were identified, with the majority of cases involving clopidogrel (260; 80.7%). Hemorrhage occurred in 16 cases (4.9%), including 7 cases of clopidogrel, 6 cases of rivaroxaban, 2 cases of dabigatran, and 1 case of apixaban. Most cases of hemorrhage were classified as major (n=9). Comparing the novel anticoagulants with the P2Y12 receptor inhibitors, the relative risk for any bleeding with novel anticoagulant was 6.68 (95% confidence interval 2.63 to 17.1); the relative risk of major bleeding was 18.1 (95% confidence interval 3.85 to 85.0). CONCLUSION: Acute overdose of novel anticoagulants or antiplatelet agents is associated with a small risk of significant hemorrhage. The risk is greater with the factor Xa inhibitors and direct thrombin inhibitors than with the P2Y12 receptor antagonists.

Thrombin generation test: A reliable tool to evaluate the pharmacodynamics of vitamin K antagonist rodenticides in rats.

Vitamin K antagonist rodenticide pharmacodynamics (PD) is studied in rodents with traditional laboratory tests. We wondered if thrombin generation test (TGT) could add value. Difethialone (10 mg/kg) was administered per os to 97 OFA-Sprague Dawley rats. PD was studied over a 72 h-period using the Calibrated Automated Thrombogram on platelet poor plasma before and after intoxication (3 female and 3 male rats for each 13 time points) and TGT parameters were compared with the prothrombin time (PT) and vitamin K dependent factor activities previously reported. Following intoxication, preliminary tests evidenced rapid and full inhibition of thrombin generation triggered with 5 or 20 pM human recombinant tissue factor. To study the evolution of TGT parameters following difethialone intake, we adapted the test by complementing intoxicated rat samples with pooled normal rat plasma (3/1, v/v). Adapted TGT confirmed the known higher procoagulant basal level in females compared to males through higher endogenous thrombin potential (ETP) and peak height (PH) (p < 0.0001 and p = 0.0003, respectively). An exponential model fitted well the PH and ETP decay after intoxication. In contrast to PT, the decreases were observed immediately following VKA intake and had comparable time to halving values: 10.5 h (95% CI [8.2; 13.6]) for ETP and 10.4 h (95% CI [7.8; 14.1]) for PH. The decrease of FVII and FX preceded that of PH, ETP and FII while FIX decreased later on, contributing to the severe hypo-coagulability. We demonstrated that TGT performed in samples of intoxicated rats complemented with normal plasma is a reliable tool for evaluation of VKA rodenticide PD in rats.

Evaluation of Fixed-Dose Four-Factor Prothrombin Complex Concentrate for Emergent Warfarin Reversal in Patients with Intracranial Hemorrhage.

BACKGROUND: Different strategies exist for dosing four-factor prothrombin complex concentrate (PCC4) for international normalized ratio (INR) reversal in the setting of life-threatening bleeding. Fixed doses ranging from 1000 IU to 1750 IU have demonstrated efficacy similar to weight-based dosing, however, few studies look exclusively at intracranial hemorrhage (ICH). OBJECTIVE: Our aim was to evaluate whether a fixed dose of 1000 IU of PCC4 achieves INR reversal similar to weight-based dosing in patients with ICH who were anticoagulated with warfarin. METHODS: We compared a weight-based dose vs. 1000 IU PCC4 between January 2014 and January 2017. The primary end point was achieving an INR < 1.5. Secondary end points included in-hospital mortality, patient disposition, and reversal defined by INR < 1.6. RESULTS: A total of 31 patients were included in the weight-based group and 30 were included in the fixed-dose group, with baseline INRs of 2.98 and 2.84, respectively (p = 0.39). Twenty-two patients (71%) achieved an INR < 1.5 in the weight-based group vs. 16 (53%) in the fixed-dose group (p = 0.15), while 25 (81%) achieved an INR < 1.6 in the weight-based group vs. 22 (73%) in the fixed-dose group (p = 0.49). There was no difference in the number of patients discharged to home (19% vs. 20%; p = 0.95) or in-hospital mortality (26% vs. 27%; p = 0.93). CONCLUSIONS: We found a non-statistically significant difference in warfarin reversal to an INR goal of < 1.5 when comparing a fixed dose of 1000 IU PCC4 and a weight-based dose for ICH. Further studies correlating clinical outcomes with INR reversal are needed.

How I treat poisoning with vitamin K antagonists.

Severe deficiency of vitamin K-dependent proteins in patients not maintained on vitamin K antagonists is most commonly associated with poisoning by or surreptitious ingestion of warfarin, warfarin-like anticoagulants, or potent rodenticides ("superwarfarins"), such as brodifacoum. Serious bleeding manifestations are common. Superwarfarins are 2 orders of magnitude more potent than warfarin and have a half-life measured in weeks. These rodenticides are readily available household environmental hazards and are sometimes consumed accidentally or as manifestations of psychiatric disease. Immediate diagnosis and proper therapy is critically important to minimize morbidity and mortality because this condition, affecting thousands of patients annually, is reversible. Treatment with large doses of oral vitamin K1, often over months to years, to maintain a near-normal prothrombin time can reverse the coagulopathy associated with superwarfarins. Although these patients initially present to various medical specialties, the hematologist is often consulted to offer the definitive diagnosis and proper therapy.

Warfarin Poisoning with Delayed Rebound Toxicity.

BACKGROUND: 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 K1, the dose and timing of which is often guided by experience with the management of over-anticoagulation with warfarin therapy, rather than acute overdose. CASE REPORT: 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 K1. He was then treated with 5 mg vitamin K1, 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 K1. 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 K1. Understanding the pharmacokinetics of vitamin K1 in comparison with warfarin, repeat INR testing, and continued treatment with oral vitamin K1 may help avoid complications of rebound coagulopathy in warfarin overdose.

Second-generation Anticoagulant Rodenticide Poisoning in a Captive Andean Condor (Vultur gryphus).

A 28-year-old female Andean condor (Vultur gryphus) housed in an outside exhibit at the National Aviary in Pittsburgh, PA, began showing signs of weakness. Toxicosis with an anticoagulant rodenticide was suspected because its mate had died 1 day earlier from possible brodifacoum poisoning. A rapid decline in the packed cell volume, despite vitamin K1 treatment, necessitated a blood transfusion with blood from bald eagles (Haliaeetus leucocephalus) and Steller's sea eagles (Haliaeetus pelagicus). Supportive therapy after transfusion included vitamin K1 (5 mg/kg IM q12h) as well as enrofloxacin, vitamin B complex, selenium and vitamin E, and subcutaneous fluids as needed. After a 39-day treatment period, a tapering dosage of vitamin K1 was initiated, and treatment ended after 17 weeks. However, 2 weeks later, the bird suffered from a potential relapse. It was successfully treated with a repeat tapering vitamin K1 regimen lasting a total of 4 months.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Superwarfarin ingestion treated successfully with prothrombin complex concentrate.

Superwarfarin, a common component of rat poison, can cause long-lasting, severe coagulopathy and life-threatening hemorrhage when ingested. We report a case of intentional rat poison consumption with subsequent hemorrhage and hypotension requiring rapid coagulopathy reversal and resuscitation in the emergency department. In addition to traditional blood products, prothrombin complex concentrate was administered. Although prothrombin complex concentrate is increasingly used for severe hemorrhage in anticoagulated patients, it may be particularly useful in superwarfarin ingestions given the extreme, persistent coagulapathies that can occur.

Anticoagulant rodenticide toxicity in six dogs presenting for ocular disease.

OBJECTIVE: To describe cases of suspected anticoagulant rodenticide toxicity manifesting with predominantly ocular signs. MATERIALS AND METHODS: Six canine cases that presented to veterinary referral hospitals for ocular abnormalities and were diagnosed with suspected or confirmed anticoagulant rodenticide ingestion were reviewed for commonalities in presentation and outcome. RESULTS: Five dogs had unilateral ocular signs and one dog had bilateral manifestations. Signs included subconjunctival hemorrhage, exophthalmos, and commonly orbital pain without other significant physical examination findings. Prothrombin time was measured in 5 of 6 dogs and was prolonged in all. Partial thromboplastin time was measured in 4 of 6 dogs and was prolonged in all. Complete blood cell count and serum chemistry profiles demonstrated mild, if any, abnormalities. Five dogs had known anticoagulant rodenticide exposure, and rodenticide ingestion was suspected in 1 additional case based on clinical signs, clinical pathologic abnormalities, and response to treatment. Five of 6 cases were hospitalized overnight for plasma transfusions along with oral or injectable vitamin K1 , and all dogs were treated with oral vitamin K1 for 30 days. All dogs experienced complete resolution of clinical signs within 6 weeks of initiating treatment. CONCLUSIONS: Anticoagulant rodenticide toxicity can present with predominantly ocular manifestations. Rodenticide ingestion should be considered in dogs with unilateral or bilateral subconjunctival hemorrhage, exophthalmos, and orbital pain.

The optimal management of anti-thrombotic therapy after valve replacement: certainties and uncertainties.

Anti-thrombotic therapy after valve replacement encompasses a number of different situations. Long-term anticoagulation of mechanical prostheses uses vitamin K antagonists with a target international normalized ratio adapted to the characteristics of the prosthesis and the patient. The association of low-dose aspirin is systematic in the American guidelines and more restrictive in the European guidelines. Early heparin therapy is frequently used early after mechanical valve replacement, although there are no precise recommendations regarding timing, type, and dose of drug. Direct oral anticoagulants are presently contraindicated in patients with mechanical prosthesis. The main advantage of bioprostheses is the absence of long-term anticoagulant therapy. Early anticoagulation is indicated after valve replacement for mitral bioprostheses, whereas aspirin is now favoured early after bioprosthetic valve replacement in the aortic position. Early dual antiplatelet therapy is indicated after transcatheter aortic valve implantation, followed by single antiplatelet therapy. However, this relies on low levels of evidence and optimization of anti-thrombotic therapy is warranted in these high-risk patients. Although guidelines are consistent in most instances, discrepancies and the low-level of evidence of certain recommendations highlight the need for further controlled trials, in particular with regard to the combination of antiplatelet therapy with oral anticoagulant and the early post-operative anti-thrombotic therapy following the procedure.