Clinlab Navigator

Bleeding Associated with New Oral Anticoagulants

Dabigatran Etexilate (Pradaxa®) is an oral direct thrombin (factor IIa) inhibitor approved by the FDA to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.Rivaroxaban, (Xarelto) is a factor Xa inhibitor, that has been approved by the FDA. Some of the pharmacokinetic properties of these drugs are compared in the following table.

 

 

Dabigatran

Rivaroxaban

GI absorption

7%

80%

Time to Peak

1-2 h

2-4 h

Half life

12-17 h

7-11 h

Excretion

80% renal, 20% bile

33% renal, 66% CYP

Protein binding

33%

80%

Data from many phase III clinical trials of dabigatran and rivaroxaban indicated that the bleeding rate was approximately 3%. Unfortunately, if bleeding does occur, no specific antidote is available. Fresh frozen plasma will not be very effective in reversing the anticoagulant effect of these drugs because of its relatively low concentration of coagulation factor II (thrombin) and factor X. Most articles written on this topic have suggested that Prothrombin Complex Concentrate (PCC) would be useful in reversing the anticoagulant effect of these drugs because it contains large doses of coagulation factors II, VII, IX and X. However, a recent publication demonstrated that PCC corrected the anticoagulant effect of rivaroxaban but not dabigatran (Circulation 2011; 124:1573-79). The authors concluded that PCC is a viable treatment for reversing the anticoagulant effect of rivaroxaban but has no role in the reversal of dabigatran.

The only remaining option for treating the bleeding associated with dabigatran is recombinant activated factor VII (rFVIIa), which achieves hemostasis by directly activating thrombin on the surface of platelets. However, the use of rFVIIa has had inconsistent results with other direct thrombin inhibitors. Other options include activated charcoal to absorb recently ingested drug and dialysis. Clearly, more research is needed in this area.

AddThis Social Bookmark Button