Stroke and Circulation are both Journals under the umbrella of the American Heart Association. So, when they publish articles that come to contrasting conclusions, I find that entertaining.
Both of these articles are mouse models of bleeding on dagibatran, C57BL/6 or CD-1 mice. Sadly, they are frighteningly complex in their adjustments and statistical analyses – which means it defeats my ability to concisely summarize the findings and methods.
In short, one of these articles looks at intracranial hemorrhage after collagenase injection for mice receiving several different doses of oral dabigatran, and compare it to controls, warfarin, lepirudin, fondaparinux, and heparin. It appears, and the author’s final conclusion is, that dabigatran is the least harmful of all anticoagulants – about halfway between controls and the other anticoagulants. They also shoot the mice with lasers in another portion of the study, and dabigatran “wins” that as well.
The other article looks at trying to reverse dabigatran – which, if you recall the human study I posted a few weeks back, was not successful in humans. However, human trials were all surrogate markers of bleeding as measured by laboratory measurements of clotting. What entertains me is, in contrast to the other study, these authors have no trouble inducing bleeding and significant ICH formation with dabigatran. In any event, once the mice were adequately bleeding, the authors compared prothrombin concentrate complexes (specifically, Beriplex), FFP, and FVIIa for treatment of ICH 30 minutes after induced injury with collagenase. Happily, PCCs, in a dose-dependent manner, attenuated the induced ICH, while the others failed.
So, perhaps this “novel, reversible” anticoagulant has a treatment option for life-threatening bleeding. Human confirmation, at least case reports, needed.
“Anticoagulation With the Oral Direct Thrombin Inhibitor Dabigatran Does Not Enlarge Hematoma Volume in Experimental Intracerebral Hemorrhage”
http://circ.ahajournals.org/content/early/2011/09/11/CIRCULATIONAHA.111.035972.abstract
“Hemostatic Therapy in Experimental Intracerebral Hemorrhage Associated With the Direct Thrombin Inhibitor Dabigatran”