Direct (New) Oral Anticoagulants (DOACs): Drawbacks, Bleeding and Reversal

Abstract

Background and Objective: Direct (new) Oral Anticoagulants (DOACs) have emerged as a contemporary and promising option in the treatment of thromboses and VTE, while protecting the coagulation cascade against untoward bleeding events. They are used in the management and prophylaxis of Venous Thromboembolism (VTE) and other thrombotic diseases. The most prominent complication of these agents is bleeding. These agents have similar or lower rates of major intracranial hemorrhages, while they had a higher risk of major gastrointestinal bleeding when compared to warfarin. This manuscript is aimed to revise and update the literature findings to outline the side effects of DOACs in various clinical scenarios. Methods: A narrative review of currently published studies was performed. Online database searches were performed for clinical trials published before July 2021, on the efficacy and adverse effects attributed to the anticoagulant treatment, especially DOACs. A literature search via electronic databases was carried out, beginning with the usage of the agents in the Western Languages papers. The search terms initially included direct (new) oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, idarucizumab, andexanet, prothrombin complex concentrates, and fresh frozen plasma. Papers were examined for methodological soundness before being included. Results: Severe bleeding episodes require aggressive interventions for successful management. Therefore, bleeding should be evaluated in special regard to the location and rate of hemorrhage, and total volume of blood loss. Patient's age, weight and organ dysfunctions (e.g., kidney/liver failure or chronic respiratory diseases) directly affect the clinical course of overdose. Conclusion: Management recommendations for hemorrhage associated with DOAC use vary, depending on the class of the culprit agent (direct thrombin inhibitor vs. FXa inhibitor), the clinical status of the patient (mild/ moderate vs. severe/life-threatening), and capabilities of the institution. Specific reversal agents (i.e., idarucizumab and andexanet alfa) can be used if available, while prothrombin complex concentrates, fresh frozen plasma and/ or tranexamic acid can also be employed as nonspecific replacement agents in the management of DOAC-related bleeding diathesis.

Non-traumatic extraocular muscle haemorrhage associated with anticoagulation use

“…Since their approval by the Food and Drug Administration in 2010, DOACs have been increasingly used for the prophylaxis and treatment of venous thromboembolism, in addition to their role in other thrombotic diseases 7 8. As with other anticoagulants, the most prominent complication of DOAC is bleeding 8. In their guidelines, the British Society of Gastroenterology recommended restarting DOAC 7 days after acute lower gastrointestinal bleeding 9.…”

Hämostaseologie in der neonatologischen und pädiatrischen Intensivmedizin

“…In der Therapie ist eine kritische Nutzen-Risiko-Abwägung zwischen Blutungsrisiko und vorhandenem Thromboserisiko notwendig. In Abhängigkeit des jeweiligen antithrombotischen Medikaments sollten folgende Maßnahmen erwogen werden [31]:…”

The Crosstalk between Nephropathy and Coagulation Disorder: Pathogenesis, Treatment, and Dilemmas

“…57,58 Compared with warfarin, DOACs cause a lower incidence of severe intracranial hemorrhage, eliminating the need for drug monitoring, which simplifies the treatment of patients with CKD with VTE or AF. 59 But the differences between DOACs have not been compared. With the continuous decline of renal function, bleeding risk is elevated in patients with CKD because of the accumulation of uremic toxins.…”