title: Clinical experience of life-threatening dabigatran-related bleeding at a large, tertiary care, academic medical center: a case series.
abstract: BACKGROUND
  Dabigatran, an oral direct thrombin inhibitor, is FDA approved for the prevention of stroke in patients with nonvalvular atrial fibrillation. No agent exists for the reversal of dabigatran-related major bleeding. Prothrombin complex concentrate (PCC) has been studied in reversal but was not shown to affect the surrogate markers of bleeding such as the thrombin time, ecarin clotting time, or activated partial thromboplastin time (aPTT). Recombinant factor VIIa (rFVIIa) may provide benefit in patients with life-threatening or major bleeding; however, it has not been studied in dabigatran-related bleeding. PCC and rFVIIa are agents utilized at our institution for major bleeding in patients receiving anticoagulant therapy. Due to the high cost and thrombogenic risk of both rVIIa and PCC and lack of a clear reversal strategy, we reviewed the management of all reported cases of dabigatran-related bleeding.
  
  
  METHODS
  This was a retrospective chart review of patients admitted to UMass Memorial Medical Center with a bleeding event and also receiving dabigatran therapy.
  
  
  RESULTS
  Eleven patients on dabigatran admitted for bleeding were identified. Seven were admitted for an intracranial hemorrhage (ICH) and four for a gastrointestinal hemorrhage (GIH). The baseline characteristics are as follows: mean age was 74.55 years (range, 63-89), and seven were male. Admission mean hemoglobin was 11.88 g/dl (range, 6.1-18), mean international normalized ratio (INR) was 2.2 (range, 1.1-7.1), and mean aPTT was 42.21 s (range, 36-81.4). Interventions received included fresh frozen plasma (n = 6), platelets (n = 3), packed red blood cells (n = 4), rFVIIa (n = 2), intravenous fluids (n = 10), surgical intervention (n = 3), and dialysis (n = 2). No patients received PCC. Four patients survived in the ICH group, and four patients survived in the GIH group.
  
  
  CONCLUSIONS
  Reversal strategies for dabigatran-related bleeding events at our institution are highly variable. Intracranial hemorrhage in patients on dabigatran was associated with 43 % mortality. Patients with severe dabigatran-related bleeding may benefit from a standardized approach to treatment.
authors.affiliation: UMass Memorial Medical Center, 55 Lake Ave. N, Worcester, MA, 01655, USA, britney.ross@umassmemorial.org.
authors.forename: Britney
authors.initials: B
authors.lastname: Ross
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Miller
authors.forename: Kristen
authors.initials: K
authors.lastname: Ditch
authors.forename: Maichi
authors.initials: M
authors.lastname: Tran
mesh_terms: D000046:Academic Medical Centers; D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000009:adverse effects*; D001562:Benzimidazoles / Q000009:adverse effects*; D003131:Combined Modality Therapy; D000069604:Dabigatran; D017809:Fatal Outcome; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D008404:Massachusetts; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D062606:Tertiary Care Centers; D016896:Treatment Outcome; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D000069604:Dabigatran