title: Use of continuous veno-venous haemodiafiltration therapy in dabigatran overdose.
abstract: BACKGROUND
  Dabigatran etexilate is one of the newer oral anticoagulants and a direct thrombin inhibitor. Concerns regarding dabigatran's use include its lack of validated laboratory markers for measuring its anticoagulation effect, the impact of renal impairment on its clearance, and the lack of effective strategies for reversal of anticoagulation. Hemodialysis has been utilized to reverse the anticoagulant effects of dabigatran in therapeutic doses. However, hemodialysis may not be feasible in hemodynamically unstable patients. There is little data on clearance rates of dabigatran by continuous renal replacement therapies.
  
  
  METHODS
  A 66-year-old male presented following a poly-pharmacy overdose of 9 g of dabigatran in combination with metoprolol, amlodipine, olmesartan, and moxonidine. Eleven hours post overdose extracorporeal elimination was implemented as the patient developed worsening coagulopathy with an elevated international normalized ratio of 11 IU, an activated partial thromboplastin time of 115 s, and had renal impairment with a creatinine of 158 μmol/L. As the patient was hemodynamically unstable, continuous veno-venous hemodiafiltration was preferred over intermittent hemodialysis. Renal replacement therapy was performed for 32 h in total and the patient made a full recovery with no hemorrhagic complications or end organ injury. This patient developed a peak serum dabigatran level of 1560 ng/ml, 11 h postoverdose. Clearance of dabigatran via continuous veno-venous hemodiafiltration was calculated, using both the recovery and A-V pair methods, with a mean clearance of 58.1 and 31.9 ml/h, respectively, and a calculated mean extraction ratio of 0.2.
  
  
  CONCLUSIONS
  There are few case reports and little experience when dabigatran is taken in overdose. This is a case report of a large dabigatran overdose presenting data on the extraction ratio and clearance of dabigatran using continuous veno-venous hemodiafiltration.
authors.affiliation: Department of Emergency Medicine, Clinical and Experimental Toxicology Unit, Prince of Wales Hospital , Randwick, NSW , Australia.
authors.forename: A L
authors.initials: AL
authors.lastname: Chiew
authors.forename: D
authors.initials: D
authors.lastname: Khamoudes
authors.forename: B S H
authors.initials: BS
authors.lastname: Chan
mesh_terms: D000368:Aged; D000991:Antithrombins / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D001562:Benzimidazoles / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D000069604:Dabigatran; D062787:Drug Overdose / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D017583:Hemodiafiltration; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D019338:Polypharmacy; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics / Q000506:poisoning*; D051437:Renal Insufficiency / Q000503:physiopathology; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D011725:Pyridines; D000069604:Dabigatran