Idarucizumab 2.5g/50ml solution for infusion vials

ObjectivesLiterature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize the current evidence and provide literature-based recommendations for the management of patients on DOACs in the perioperative phase.MethodsA general literature review was conducted on the pharmacology of DOACs and for recommendations on the management of cardiac surgical patients on DOACs. Additionally, we performed a systematic review for studies on the use of direct DOAC reversal agents in the emergency cardiac surgical setting.ResultsWhen surgery is elective, the DOAC cessation strategy is relatively straightforward and should be adapted to the renal function. The same approach applies to urgent cases, but additional DOAC activity drug level monitoring tests may be useful. In emergency cases, idarucizumab can be safely administered to patients on dabigatran in any of the perioperative phases. However, andexanet alfa, which is not registered for perioperative use, should not be administered in the preoperative phase to reverse the effect of factor Xa inhibitors, as it may induce temporary heparin resistance. Finally, the administration of (activated) prothrombin complex concentrate may be considered in all patients on DOACs, and such concentrates are generally readily available.ConclusionsDOACs offer several advantages over vitamin K antagonists, but care must be taken in patients undergoing cardiac surgery. Although elective and urgent cases can be managed relatively straightforwardly, the management of emergency cases requires particular attention.

Abstract licence: CC BY-NC

BACKGROUND AND PURPOSE: Current guidelines do not recommend the use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who receive direct oral anticoagulants. While the humanized monoclonal antibody idarucizumab can quickly reverse the anticoagulant effects of the thrombin inhibitor dabigatran, safety data for subsequent tissue plasminogen activator treatment are sparse. Here, we review current knowledge about dabigatran reversal prior to systemic reperfusion treatment in acute ischemic stroke. METHODS: We performed a systematic review of all published cases of intravenous tissue plasminogen activator treatment following the administration of a dabigatran antidote up to June 2017 and added five unpublished cases of our own. We analyzed clinical and radiological outcomes, symptomatic post-thrombolysis intracranial hemorrhage, and other serious systemic bleeding. Additional endpoints were allergic reaction to idarucizumab, and venous thrombosis in the post-acute phase. RESULTS: We identified a total of 21 patients (71% male) with a median age of 76 years (interquartile range 70-84). The median National Institute of Health Stroke Scale score at baseline was 10 (n = 20, interquartile range 5-11) and 18/20 patients (90%) had mild or moderate stroke severity. The time from symptom onset to start of tissue plasminogen activator was 155 min (n = 18, interquartile range 122-214). The outcome was unfavorable in 3/19 patients (16%). There was one fatality as a result of a symptomatic post-thrombolysis intracranial hemorrhage, and two patients experienced an increase in the National Institute of Health Stroke Scale compared with baseline. One patient had a recurrent stroke. No systemic bleeding, venous thrombosis, or allergic reactions were reported. CONCLUSION: Experience with idarucizumab administration prior to tissue plasminogen activator treatment in acute ischemic stroke is limited. Initial clinical experience in less severe stroke syndromes and short time windows seems favorable. Larger cohorts are required to confirm safety, including bleeding complications and the risk of thrombosis.

Abstract licence: CC BY 4.0

BackgroundDirect oral anticoagulants (DOACs) are widely used but pose significant challenges in emergency neurosurgical settings. Idarucizumab and andexanet alfa are approved reversal agents, yet their effectiveness and safety in neurosurgical emergencies remain unclear.ObjectivesThis systematic review evaluates the current evidence on DOAC reversal in patients undergoing emergency neurosurgical interventions.MethodsWe conducted a systematic review of case series of a minimum of 5 patients on DOACs receiving andexanet or idarucizumab for emergency neurosurgery (ResultsSeven studies, comprising 148 patients, met the inclusion criteria. Andexanet was investigated in 4 studies, including 37 patients. Adequate intraoperative hemostasis was confirmed in 80% to 100% of patients. One study showed a thromboembolic event rate of 8.3% and an in-hospital mortality rate of 50% in 12 patients, while others showed lower rates. Idarucizumab was analyzed in 3 studies of 111 patients, of whom 97 were from a single large cohort. Satisfactory hemostasis was reported in 93.5% to 100% of patients. Thromboembolic event rates ranged from 0% to 4.1% and mortality rates were 0%, 3.1%, and 12.5%, respectively.ConclusionThe use of DOAC reversal agents in emergency neurosurgery appears feasible and may support surgical hemostasis in selected patients. However, further research is warranted, particularly regarding the off-label use of andexanet, given the limited evidence and potential safety concerns.

Abstract licence: CC BY