New oral anticoagulants: clinical indications, monitoring and treatment of acute bleeding complications

Abstract

New oral anticoagulants like the direct thrombin inhibitor, dabigatran (Pradaxa®), and factor Xa-inhibitors, rivaroxaban (Xarelto®) and apixaban (Eliquis®) are available for prophylaxis and treatment of thromboembolic disease. They are emerging alternatives to warfarin and provide equal or better clinical outcome together with reduced need for routine monitoring. Methods for measuring drug concentrations are available, although a correlation between plasma drug concentrations and the risk of bleeding has not been firmly established. Standard laboratory measures like prothrombin time and activated partial thromboplastin time are not sensitive enough to detect thrombin or factor Xa inhibition provided by new oral anticoagulants. Thus, these standard tests may only be used as a crude estimation of the actual anticoagulation status. Further challenges regarding patients receiving new oral anticoagulants who presents with major bleeding or need for emergency surgery pose a unique problem. No established agents are clinically available to reverse the anticoagulant effect, although preclinical data report prothrombin complex concentrate as more efficient than fresh frozen plasma or other prohaemostatic agents. This review summaries current knowledge on approved new oral anticoagulants and discusses clinical aspects of monitoring, with particular focus on the management of the bleeding patient.

Complications With New Oral Anticoagulants Dabigatran and Rivaroxaban in Cutaneous Surgery

“…13 Data from O'Dell and colleagues. 16 T max , the time after administration of a medication when the maximum plasma concentration is reached;…”

“…[8][9][10][11] Outcomes of major bleeding events also have been reported to be better with dabigatran than with warfarin, resulting in shorter stays in intensive care and lower mortality. 12,13 Thus, treatment with these new oral anticoagulants is an attractive alternative to treatment with vitamin K antagonists. Cutaneous surgeons will likely encounter increasing numbers of patients on these medications.…”

“…Clinical indications include stroke prevention in AF, VTE prophylaxis after hip or knee replacement, and treatment of VTE. 9,[11][12][13][14][15] Important concerns have been raised regarding these new oral anticoagulants. Patients receiving one of the new oral anticoagulants constitute a new challenge because of the lack of specific antidotes.…”

“…9,11 Hemodialysis may be useful for removal of dabigatran, but it is not indicated for removal of rivaroxaban because of its high degree of protein binding. 13 Complications with dabigatran during cutaneous surgery have been discussed, with 1 report of an elderly patient on dabigatran in whom a subarachnoid hemorrhage developed during dermabrasion for scar revision. 19 However, it could not be determined whether the events were related.…”

Oral anticoagulants for primary prevention, treatment and secondary prevention of venous thromboembolic disease, and for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis and cost-effectiveness analysis

“…Specific tests to measure the anticoagulation effects of NOACs are being developed but are not yet widely available 234 and routine coagulation tests such as prothrombin time and activated partial thromboplastin time are of limited use. 235,236 It is therefore currently unclear whether or not the efficacy Finally, therapeutic decision making may be influenced by recognition that effective treatments for reversal of anticoagulation with NOACs are still in the developmental phase. For example:…”