What’s Pradaxa? Can I make people stop bleeding?

21 Jun

KEY POINTS:

Mechanism of action of Pradaxa (dabigatran):

  • The drug itself is a pro-drug that is converted into an active metabolite in vivo
  • The active metabolite is a direct thrombin inhibitor that inhibits free and fibrin-bound thrombin
  • inhibits anticoagulation by preventing thrombin-mediated effects including cleavage of fibrin to fibrin monmomers, activation of V, VIII, XI, and XIII, and inhibition of thrombin-induced platelet aggregation.

Several potential antidotes have been studied for reversal:

  • Recombinant Factor VIIa
    • Had no effect on the prevention of excess hematoma expansion induced by dabigatran in one study
    • However, in a study using blood from healthy volunteers, rFVIIa successfully reversed the actions of dabigatran by reducing clot initiation time to baseline levels
  • Prothrombin Concentrate Complexes
    • In one study, PCC’s failed to reduced the effects of Pradaxa
    • PCC however was successful in reversing the effects of dabigatran in a model of intracerebral hemorrhage, where excess hematoma expansion was prevented
    • Overall, more research is needed to determine correct dosing of PCC’s to reverse Pradaxa.

BOTTOM LINE:

When faced with a patient with serious or life-threatening bleeding who is on Pradaxa, rFVIIa and PCC’s seem to be the only potential treatments, though the data is not conclusive

Submitted by W. Brooks.

Reference(s): UpToDate; Reversal of Antithrombotic agents, Kenneth Bauer, American Journal of Hematology, Volume 87, Issue S1, p S119-S126, May 2012; picture

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