Faculty Bibliography

STUDY OBJECTIVE/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/CONCLUSIONS: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.

INTRODUCTION: Epidemiologic studies of snakebites in the United States report typical victims to be young men. Little is known regarding other demographics including children and the elderly. The objective of this study was to describe the epidemiology and clinical manifestations of snake bite in elderly patients reported to the ToxIC (Toxicology Investigators Consortium) North American Snakebite Registry (NASBR) Methods: This was a multicenter analysis of a prospectively collected cohort of patients with snakebite reported to the ToxIC NASBR between 1 January 2013 and 31 December 2015. Inclusion criterion was age >65. Variables collected included patient demographics, medical comorbidities, medications, date the case was reported to the registry, location of exposure, bite location, snake species, clinical manifestations, outcomes, and management. RESULTS: Of the 450 cases reported, 30 (6.7%) occurred in elderly patients, with an average age of 74 years. Rattlesnake envenomations were common (93.3%). The majority of patients were men (66.7%) and reported at least one medical comorbidity (83.3%). Most patients were on cardiac medications (60%) and use of antiplatelet or anticoagulant medications was common (33%). Hemotoxicity occurred in 30% of patients on initial presentation and 11.5% of patients on initial follow-up. No clinically significant early or late bleeding was observed. CONCLUSIONS: Elderly patients with North American snake envenomation are likely to have co-morbidities and to take medications that may increase their risk for hemotoxicity, however risk of bleeding or other complications was not increased in this group.

The American College of Medical Toxicology established the North American Snakebite Registry (NASBR), a national database of detailed, prospectively collected information regarding snake envenomation in the United States, in 2013. This report describes the epidemiology, clinical course, and management of snakebites in the NASBR. All cases entered into the NASBR between January 1, 2013 and December 31, 2015 were identified. Descriptive statistics are used to report results. Fourteen sites in 10 states entered 450 snakebites. Native species comprised 99% of cases, almost all of which were pit viper bites. 56.3% were identified as rattlesnakes and 29.4% as copperheads. 69.3% were male and 28.2% were children age 12 and under. Fifty-four percent of bites were on the lower extremity. Twenty-seven percent of patients with lower extremity bites were not wearing shoes. Common tissue findings associated with envenomation were swelling, ecchymosis, and erythema. Systemic effects and hematologic toxicity were more common in rattlesnake than copperhead or cottonmouth envenomations. Crotalidae Polyvalent Immune Fab antivenom was given to 84% of patients. Twelve patients (4.3%) were re-admitted to the hospital after completion of treatment. Eight were re-treated with antivenom. The NASBR gathers detailed data on venomous snakebites across the US. In its initial years, useful information has already been gained. Data regarding footwear will inform public health interventions and education, and information regarding the clinical presentation may help physicians better anticipate effects and manage snakebite. As the number of cases in the NASBR grows, associations between patient-related factors and outcomes may be studied.

Metabolic biomarkers have potentially wider use in disease diagnosis and prognosis as well as in monitoring disease response to treatment. While biomarkers such as interleukins, microRNA, and lactate have been proposed for disease surveillance, there are still conflicting results regarding their clinical utility. Treatment of commonly encountered disease of acute care such as sepsis, trauma, and poisoning often relies on clinical diagnosis and therapy guided by use of surrogate markers of illness severity. The measurement of mitochondrial function, including respiration and motility, may offer superior alternatives to such markers. Assessing mitochondrial function in a clinical context has the potential to impact the area of acute care in terms of diagnosis, prognosis, and treatment. The study of mitochondrial bioenergetics has become critical in understanding the pathophysiology and treatment of complex diseases such as diabetes and cardiovascular disorders.