An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers.

STUDY OBJECTIVE: Rivaroxaban and apixaban are part of a new group of oral anticoagulants targeting factor Xa and approved by the Food and Drug Administration in 2011 and 2012. These oral anticoagulants are administered at fixed daily doses, without the need for laboratory-guided adjustments. There are limited data available on supratherapeutic doses or overdose of the oral Xa inhibitors. This study characterizes the clinical effect in patients exposed to rivaroxaban and apixaban. METHODS: A retrospective study collected data from 8 regional poison centers covering 9 states. Cases were initially identified by a search of the poison centers' databases for case mentions involving a human exposure to Xarelto, rivaroxaban, Eliquis, or apixaban. Inclusion criteria included single-substance exposure. Exclusion criteria were animal exposure, polysubstance exposure, or information call. Data for the study were collected by individual chart review, including case narratives, and compiled into a single data set. RESULTS: There were 223 patients: 124 (56%) were female patients, mean age was 60 years, and 20 were children younger than 12 years (9%). One hundred ninety-eight patients ingested rivaroxaban (89%) and 25 ingested apixaban (11%). Dose was reported in 182 rivaroxaban patients, with a mean dose of 64.5 mg (range 15 to 1,200 mg), and in 21 apixaban patients, with a mean dose of 9.6 mg (range 2.5 to 20 mg). For rivaroxaban, prothrombin time was measured in 49 patients (25%) and elevated in 7; partial thromboplastin time, measured in 49 (25%) and elevated in 5; and international normalized ratio, measured in 61 (31%) and elevated in 13. For apixaban, prothrombin time was measured in 6 patients (24%) and elevated in none; partial thromboplastin time, measure in 6 (24%) and elevated in none; and international normalized ratio, measured in 5 patients (20%) and elevated in none. Bleeding was reported in 15 patients (7%): 11 rivaroxaban and 4 apixaban. The site of bleeding was gastrointestinal (8), oral (2), nose (1), bruising (1), urine (1), and subdural (1). The subdural bleeding occurred after fall and head injury. All cases with bleeding involved long-term ingestions. Coagulation test results were normal in most patients with bleeding: prothrombin time 5 of 6 (83%), partial thromboplastin time 5 of 6 (83%), and international normalized ratio 5 of 9 (55%). Blood products were used in 7 rivaroxaban patients (1 suicide) and 3 apixaban patients. No bleeding or altered coagulation test results occurred in children, which all involved a one-time ingestion. All 12 suicide attempts involved rivaroxaban: altered coagulation test results occurred for 5 patients (42%), no bleeding occurred in any suicide attempt patient, 1 patient was treated with fresh frozen plasma (international normalized ratio 12.47), and dose by patient history did not predict risk of altered coagulation or bleeding. Two rivaroxaban patients experienced elevation of hepatic transaminase levels greater than 1,000 U/L. CONCLUSION: Bleeding after Xa inhibitor ingestion as a single agent is uncommon. Prothrombin time, partial thromboplastin time, or international normalized ratio may be elevated in a minority of cases but appears unreliable to measure risk of bleeding. Massive acute ingestion in suicide attempt may result in significant anticoagulation. Single exploratory ingestion by children was not associated with toxicity.

A 9-state analysis of designer stimulant, "bath salt," hospital visits reported to poison control centers.

STUDY OBJECTIVE: A new generation of designer stimulants marketed as "bath salts" emerged in late 2010. The goal is to describe the epidemiologic emergence of designer stimulants in 9 states in the Midwest. METHODS: A retrospective review of the National Poison Data System was performed between November 1, 2010, and November 30, 2011. Inclusion criteria were health care-evaluated bath salts or other synthetic stimulants exposures. Cases were excluded if the exposure was unrelated to a designer stimulant. Demographic and clinical characteristics of cases were calculated and differences in outcome and exposure by generation were examined. RESULTS: One thousand six hundred thirty-three patients met the inclusion criteria. Age ranged from 1 day to 61 years (mean=29.2 years), with 67.9% male patients. The most common clinical features were agitation (62.2%), tachycardia (55.2%), and hallucinations (32.7%). In addition to 15.5% of patients having a major medical effect, 0.6% died. Reason for use was primarily intentional abuse (88.5%). However, 0.7% of patients reported withdrawal. Treatment involved primarily benzodiazepines (58.5%), with 8.7% of patients being intubated. Baby Boomers were more likely to have a major medical outcome (24.2%) and to report injection as the method of administration (8.6%-12.9%). CONCLUSION: Synthetic stimulants rapidly swept across the Midwest, resulting in more than 1,600 patients seeking medical care. Serious medical effects or death was observed in 16.1% of cases. Older generations were more likely to inject and to have a major medical outcome.

Population data from the New South Wales Aboriginal Australian sub-population for the profiler plus autosomal short tandem repeat (STR) loci.

It is a requirement that forensic DNA profiling evidence be accompanied by an estimation of its weight, in order that the court can assign an appropriate probative value to it during legal proceedings. There are various models by which this estimation can be made, but each relies on approximations of the allele frequencies in the relevant population. This report provides the results of population genetic analyses at nine autosomal short tandem repeat (STR) loci for the Aboriginal Australian sub-population of New South Wales, Australia.

Mitigation of pennyroyal oil hepatotoxicity in the mouse.

OBJECTIVES: Pennyroyal oil ingestion has been associated with severe hepatotoxicity and death. The primary constituent, R-(+)-pulegone, is metabolized via hepatic cytochrome P450 to toxic intermediates. The purpose of this study was to assess the ability of the specific cytochrome P450 inhibitors disulfiram and cimetidine to mitigate hepatotoxicity in mice exposed to toxic levels of R-(+)-pulegone. METHODS: 20-g female BALB/c mice were pretreated with either 150 mg/kg of cimetidine intraperitoneal (IP), 100 mg/kg of disulfiram IP, or both. After one hour, mice were administered 300 mg/kg of pulegone IP and were killed 24 hours later. Data were analyzed using ANOVA. Post-hoc t-tests used Bonferroni correction. RESULTS: There was a tendency for lower serum glutamate pyruvate transaminase in the disulfiram and cimetidine groups compared with the R-(+)-pulegone group. The differences were significant for both the cimetidine and the combined disulfram and cimetidine groups compared with the R-(+)-pulegone group. Pretreatment with the combination of disulfiram and cimetidine most effectively mitigated R-(+)-pulegone-induced hepatotoxicity. CONCLUSIONS: Within the limitations of a pretreatment animal model, the combination of cimetidine and disulfiram significantly mitigates the effects of pennyroyal toxicity and does so more effectively than either agent alone. These data suggest that R-(+)-pulegone metabolism through CYP1A2 appears to be more important in the development of a hepatotoxic metabolite than does metabolism via CYP2E1.