**6. Bleeding complications and antidotes**

The fear of bleeding complications is one of the most prevalent obstacles in anticoagulant treatment in AF, especially cerebral hemorrhage.

These drugs have no specific antidotes which is a problem in patients who are at high risk of bleeding or hemorrhagic. Dabigatran is a dialyzable drug, which can eliminate up to 60% of the molecule in serum. Other possibilities include the use of activated coal and of neutraliz‐ ing antibodies but are lacking in vivo experience. With respect to rivaroxaban is working in a variant of factor Xa would compete with the normal to factor Xa when joining rivaroxaban and thus the effect would be reversed.

In order to reverse the effect of NOACs designed a crossover trial, randomized, doubleblind, placebo-controlled study included 12 healthy male volunteers. Received rivaroxaban 20 mg/12h or dabigatran 15 mg/12h for 2.5 days followed by a single bolus of 50 IU/kg of prothrombin complex concentrate (PCC) or similar volume of saline. The results concluded that the PCC completely and immediately reversed the anticoagulant effect of ribaroxaban but had no influence on the effect of dabigatran at the doses used in this study. These results should be analyzed with caution due to small sample size (12 patients) and the characteris‐ tics of the population that was part of the study (only male patients and healthy). [27]. An‐ other study found the low doses of non-specific reversal agents (anticoagulant anti-inhibitor complex with non-activated factors II, IX and X and activated factor VII) appear to be able to reverse the anticoagulant activity of rivaroxaban or dabigatran. However, clinical evaluation is needed regarding haemorrhagic situations, and a meticulous risk-benefit evaluation [28]. The absence of normalization of coagulation tests not necessarily correlate with the absence of anti-haemorrhagic effect, as demonstrated in animal models [24].

Thus, in a patient treated with dabigatran and rivaroxaban that presents a mild bleeding complication, it is advisable to delay the next drug administration or discontinuation. If bleeding is moderate or severe, symptomatic treatment is indicated as mechanical compres‐ sion standard, surgical hemostasis bleeding control procedure, blood products and hemody‐ namic support (packed red cells or fresh frozen plasma). In the case of very severe bleeding will require charcoal filtration or haemodialysis or administration of an agent for reversing the specific procoagulant effect, such as prothrombin complex, the prothrombin complex concentrate or activated recombinant factor VIIa. In this case, experience is limited.
