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Review of the Pharmacology of the Emerging Possibilities of the Direct Oral Anticoagulants' Reversal

[ Vol. 18 , Issue. 7 ]

Author(s):

Matej Samos*, Lucia Stanciakova, Ingrid Skornova, Tomas Bolek, Frantisek Kovar, Jan Stasko, Peter Galajda, Marian Mokan and Peter Kubisz   Pages 643 - 650 ( 8 )

Abstract:


Background: Direct oral anticoagulants (DOACs) offer consistent and predictable anticoagulation, oral administration with good patient compliance and a good safety profile. Dabigatran - a direct thrombin inhibitor, apixaban and rivaroxaban - direct factor Xa inhibitors are now largely used for anticoagulation in patients with nonvalvular atrial fibrillation and in patients with venous thromboembolism. These agents have emerged as an expediential clinical choice in long-term anticoagulation for an increasing number of patients. Despite their advantages, concerns persist about a lack of rapid reversal agents in urgent clinical situations.

Methods: This review is focused on the pharmacology of nonspecific and target-specific reversal agents for DOACs-induced anticoagulation. A systemic review of preclinical and clinical studies published in peer-reviewed scientific journals was performed.

Results and Conclusions: Fresh frozen plasma and coagulation factors concentrates might be considered in bleeding emergencies; however, there is a lack of larger studies confirming the efficacy of coagulation factors concentrates for the reversal of DOACs-induced anticoagulation, and a particular risk of coagulation factors concentrates-induced thrombosis. Recently, idarucizumab has been approved commercially for acute reversal of dabigatran in emergencies as a first target-specific reversal agent. Moreover, andexanet alpha and aripazine are being extensively studied in several phase II and III clinical studies. It is likely that more target-specific agents for reversal of DOACs-induced anticoagulation will be introduced to clinical practice in near future.

Keywords:

Dabigatran, DOACs-related bleeding, new oral anticoagulants reversal, idarucizumab, adnexanet alpha, aripazine.

Affiliation:

Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 036 59 Martin, National Centre of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, National Centre of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, National Centre of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Department of Internal Medicine I, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, National Centre of Hemostasis and Thrombosis, Department of Hematology and Blood Transfusion, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin

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