2- Direct Oral Anticoagulants (DOACs):
Direct thrombin inhibitor: Dabigatran (Pradaxa )
The antidote (Idarucizumab ) was studied in patients with dabigatran–associated bleeding (REVERSE-AD trial). Most common sites of bleeding were gastrointestinal and intracranial. Median time to achieve hemostasis was 2.5 hours and there was no correlation with drug levels. None underwent CPB and several patients suffered thromboembolic events, 50% of which occurred within 5 days.32 In a multicenter experience in Spain, Idarucizumab was used in 56 transplant patients, 7.5% required reoperations for bleeding and 66% were transfused with blood products.33
Factor Xa inhibitors: Apixaban (Eliquis ), Edoxaban (Savaysa ), Rivaroxaban (Xarelto ), Edoxaban (Bevyxxa).
The use of Andexanet Alfa (a recombinant modified factor Xa protein) as an antidote was reported on 352 patients on factor Xa inhibitors who had major bleeding (64% intracranial and 26% gastrointestinal). It markedly reduced factor Xa activity with good or excellent hemostatic effects in 82% patients.34 In one prospective study of 66 patients on factor Xa inhibitors and presenting with major bleeding, reversal was effective in 68%, ineffective in 32% and 8% suffered a major thromboembolic event.28 Ciraparantag is a promising universal antidote to all DOACs that binds to the anticoagulants via noncovalent hydrogen bonds and is under FDA review. (Table 3)
Hemodialysis (HD) is thought not to be very beneficial with regards to urgent reversal as most DOACs, including rivaroxaban and apixaban, are highly protein bound. Although edoxaban is relatively low protein bound, it is not well cleared by HD. Betrixiban is 60% protein bound, but there is a paucity of data demonstrating the effectiveness of dialysis in clearing the drug. Dabigatran is 35% protein bound and HD has been proposed as a possible treatment strategy in patients with major bleeding. Published reports have shown that 4-hours of HD can reduce the plasma concentration of dabigatran up to 68%, with a recent meta-analysis suggesting HD may be of some benefit in patients requiring urgent reversal.35