title: Reversal of dabigatran-associated major bleeding with activated prothrombin concentrate: A prospective cohort study.
abstract: The reversal of dabigatran-associated major bleeding can now be achieved with the antidote idarucizumab. We evaluated activated prothrombin complex concentrate (aPCC) as an alternative for this purpose. Patients treated with dabigatran and suffering a major bleed were treated as per existing hospital protocol with aPCC. They were subsequently recruited for a 30-day follow-up. Effectiveness was evaluated by the treating physician, using an Assessment Guide. Safety outcomes were arterial or venous thromboembolism or death. A comparison was also made with historic cases with dabigatran-associated major bleeds treated with supportive care, by matching 1:2 for type of bleed, age and sex. We aimed at 32 evaluable cases but the study was prematurely discontinued after 14 cases due to the availability of the approved antidote. The effectiveness of aPCC was assessed as Good in 9 (64%), moderate in 5 (36%) and poor in none. There were no thromboembolic events and one death. In the secondary adjudication of effectiveness, using the same criteria and by the same adjudicators as previously done for the historic cases, the outcome was graded for the current cases versus the historic cases as Good, Moderate, or Poor in 10 (71%) versus 16 (57%), 3 (21%) versus 4 (14%), and 1 (7%) versus 8 (29%), respectively. Although supportive care is sufficient to manage many patients with dabigatran-associated bleeding, aPCC might provide an additional benefit to control life-threatening bleeding in selected cases and does not appear to cause an excess of thromboembolic events.
authors.affiliation: Department of Medicine, McMaster University, Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada; Department of Hematology, Karolinska Institutet, Stockholm, Sweden. Electronic address: schulms@mcmaster.ca.
authors.forename: Sam
authors.initials: S
authors.lastname: Schulman
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Ritchie
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Nahirniak
authors.affiliation: Department of Medicine, McMaster University, Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.
authors.forename: P L
authors.initials: PL
authors.lastname: Gross
authors.affiliation: Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Carrier
authors.affiliation: Department of Hematology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Majeed
authors.affiliation: Department of Medicine, Soonchunhyang University Gumi's Hospital, North Kyungsang Province, South Korea.
authors.forename: H-G
authors.initials: HG
authors.lastname: Hwang
authors.affiliation: Department of Medicine, McMaster University, Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Zondag
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000991:Antithrombins / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D000069604:Dabigatran / Q000009:adverse effects*; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011446:Prospective Studies
chemical_list: D000991:Antithrombins; D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D000069604:Dabigatran
keywords: Activated prothrombin complex concentrate; Atrial fibrillation; Bleeding; Dabigatran