title: An Observational Study of the Factor Xa Inhibitors Rivaroxaban and Apixaban as Reported to Eight Poison Centers.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Central Ohio Poison Center, Nationwide Children's Hospital, Columbus, OH; Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH. Electronic address: Haspiller5@gmail.com.
authors: Henry A
authors: HA
authors: Spiller
authors: Indiana Poison Center, Indiana University Health Methodist Hospital, and the Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN.
authors: James B
authors: JB
authors: Mowry
authors: Florida Poison Information Center-Tampa, Tampa General Hospital, Tampa, FL.
authors: Alfred
authors: A
authors: Aleguas
authors: College of Pharmacy, Ohio State University, Columbus, OH; Mount Carmel Medical Center West, Columbus, OH.
authors: Jill R K
authors: JR
authors: Griffith
authors: Cincinnati Drug & Poison Information Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors: Robert
authors: R
authors: Goetz
authors: Louisiana Poison Center, Shreveport, LA.
authors: Mark L
authors: ML
authors: Ryan
authors: Minnesota Poison Control System, Hennepin County Medical System, Minneapolis, MN.
authors: Stacey
authors: S
authors: Bangh
authors: Maryland Poison Center and the University of Maryland School of Pharmacy, Baltimore, MD.
authors: Wendy
authors: W
authors: Klein-Schwartz
authors: Oklahoma Center for Poison & Drug Information, Oklahoma City, OK.
authors: Scott
authors: S
authors: Schaeffer
authors: Central Ohio Poison Center, Nationwide Children's Hospital, Columbus, OH; College of Pharmacy, Ohio State University, Columbus, OH; Ohio State University College of Medicine, Columbus, OH.
authors: Marcel J
authors: MJ
authors: Casavant
mesh_terms: D000059:Accidents; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000818:Animals; D001780:Blood Coagulation Tests; D002648:Child; D062787:Drug Overdose; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000506:poisoning*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011039:Poison Control Centers; D011720:Pyrazoles / Q000008:administration & dosage / Q000506:poisoning*; D011728:Pyridones / Q000008:administration & dosage / Q000506:poisoning*; D012189:Retrospective Studies; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000506:poisoning*; D013405:Suicide; D014481:United States / Q000453:epidemiology
chemical_list: D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D000069552:Rivaroxaban