Document Detail

Reversal of Dabigatran-induced Bleeding by Coagulation Factor Concentrates in a Rat-tail Bleeding Model and Lack of Effect on Assays of Coagulation.
MedLine Citation:
PMID:  24714118     Owner:  NLM     Status:  Publisher    
BACKGROUND:: Dabigatran is a potent oral anticoagulant. Like any anticoagulant, there is an increased risk of bleeding associated with its use, and reversal may be needed in cases of severe bleeding.
METHODS:: In this study, six coagulation factor concentrates (CFCs) were tested for their ability to reduce bleeding induced by oral dabigatran etexilate (30 mg/kg) in a rat-tail bleeding model (n = 5 to 8 per group): three-factor (Profilnine [Grifols Biologicals Inc., Los Angeles, CA] and Bebulin [Baxter BioScience, Westlake Village, CA]) and four-factor prothrombin complex concentrates (Beriplex [CSL Behring, Marburg, Germany] and Octaplex [Octapharma AG, Lachen, Switzerland]), activated prothrombin complex concentrate (Factor Eight Inhibitor Bypassing Activity; Baxter AG, Vienna, Austria), and recombinant factor VIIa (NovoSeven; NovoNordisk, Bagsværd, Denmark). The effect of CFCs on prolongation of coagulation assays was measured. Thrombin generation after administration of each CFC was compared in vitro using human plasma (n = 5) spiked with dabigatran in concentrations corresponding to median peak (200 ng/ml) and supratherapeutic values (600 and 1,000 ng/ml).
RESULTS:: Dabigatran resulted in an approximately three-fold increase in bleeding time, consistent with supratherapeutic dabigatran plasma levels. Beriplex (35 and 50 IU/kg), Octaplex (40 IU/kg), Profilnine (50 IU/kg), Bebulin (60 IU/kg), Factor Eight Inhibitor Bypassing Activity (100 U/kg), and NovoSeven (500 μg/kg) significantly decreased this prolonged bleeding time over 30 min (P < 0.001). The coagulation assays were prolonged three- to eight-fold over baseline (P = 0.01). None of the CFCs produced a consistent change in these assays that was predictive of reduced bleeding. Thrombin generation reversal was dependent on the concentration of dabigatran and each CFC; normalization occurred at the lower concentration of dabigatran with most CFCs, but not at higher concentrations.
CONCLUSIONS:: In this animal model, bleeding induced by high doses of dabigatran can be reduced by CFCs. However, routine coagulation assays do not predict this effect.
Joanne van Ryn; Johanna Schurer; Monika Kink-Eiband; Andreas Clemens
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-4-7
Journal Detail:
Title:  Anesthesiology     Volume:  -     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2014 Apr 
Date Detail:
Created Date:  2014-4-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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