Dabigatran, oleh-oleh halalbihalal...

Dabigatran use is contraindicated in patients with severe renal insufficiency (creatinine clearance [CrCl] <30 ml/min), and caution should be used vdth its use in patients with moderate renal insufficiency (CrCl 30-50 ml/min). Caution should also be used when dabigatran is given to patients who are receiving drugs that affect hemostasis, such as acetylsalicyhc acid (ASA) and clopidogrel, because of the established increase in serious bleeding that occurs when antithrombotic drugs are combined.

Interestingly, the dabigatran drug capsule consists of small (0.8 mm) pellets of a tartaric acid core coated with dabigatran. The tartaric acid creates an acidic microenvironment that allows absorption of dabigatran, independent of gastric pH, but probably also accounts for the 6% to 12% incidence of dyspepsia observed in dabigatran-treated patients.

Dabigatran causes a dose-dependent and short-lived (1-4 hours after administration) prolongation in the activated partial thromboplastin time (aPTT) and prothrombin time (PT), whereas its effect on the INR is less clear. Monitoring the anticoagulant effect of dabigatran may involve the thrombin time (TT), which measures the conversion of fibrinogen to fibrin by thrombin (factor II).

There is currently no antidote to dabigatran that can be administered to patients who develop serious (major) bleeding during dabigatran therapy.

Patient management should include, as it does VKA-associated bleeding, administration of coagulation factor replacement, with either prothrombin complex concentrate (15 ml/kg) or fresh frozen plasma (4 units). The role for recombinant activated factor VII is unclear but it may be considered for life-threatening bleeding that continues despite blood product administration and other hemostatic measures. One additional consideration in dabigatran-treated bleeding patients with prior or newly developed renal failure is that hemodialysis may be needed to remove dabigatran that might have accumulated due to worsening renal function.