Andexanet alpha

BACKGROUND: Andexanet alfa, an anti-Xa inhibitor antagonist, induces heparin resistance. Here, we report a case of successful management of cardiopulmonary bypass with andexanet alfa-induced heparin resistance using nafamostat mesylate. CASE PRESENTATION: An 84-year-old female, with Stanford type A acute aortic dissection, underwent an emergency surgery for total aortic arch replacement. Andexanet alfa 400 mg was administered preoperatively to antagonize edoxaban, an oral Xa inhibitor...

Andexanet alfa (AA) is a recombinant, inactive analog of human factor Xa (FXa), effectively reversing the effects of its inhibitors - rivaroxaban and apixaban, which are available in Poland. The drug was granted registration after the publication of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in a group of patients using the aforementioned anticoagulants was proven. Hence, AA is now recommended for patients receiving apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding...

This study in vitro comprehensively assessed reversal of the anticoagulant effects of rivaroxaban, an oral factor Xa inhibitor, using andexanet alfa and various prothrombin complex concentrate (PCC) products in a battery of tests. In static coagulation assays, andexanet alpha outperformed PCCs except for activated PCC being more effective in standard coagulation times. However, in a flow chamber model mimicking arterial shear, both andexanet alpha and high-concentration PCC restored fibrin formation, but not platelet adhesion...

BACKGROUND: Andexanet alfa (AA), a factor Xa-inhibitor (FXi) reversal agent, is given as a bolus followed by a 2-hour infusion. This long administration time can delay EVD placement in intracerebral hemorrhage (ICH) patients. We sought to evaluate the safety of EVD placement immediately post-AA bolus compared to post-AA infusion. METHODS: We conducted a retrospective study that included adult patients admitted with FXi-associated ICH who received AA and underwent EVD placement The primary outcome was the occurrence of a new hemorrhage (tract, extra-axial, or intraventricular hemorrhage)...

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In 2018, the International Council for Standardization in Haematology (ICSH) published a consensus document providing guidance for laboratories on measuring direct oral anticoagulants (DOACs). Since that publication, several significant changes related to DOACs have occurred, including the approval of a new DOAC by the Food and Drug Administration, betrixaban, and a specific DOAC reversal agent intended for use when the reversal of anticoagulation with apixaban or rivaroxaban is needed due to life-threatening or uncontrolled bleeding, andexanet alfa...

Non-controlled hemorrhage with accompanying trauma-induced coagulopathy (TIC) remains the most common cause of preventable death after multiple injury. Rapid identification followed by aggressive treatment is the key for improved outcomes. Treatment of trauma hemorrhage begins at the scene, with manual compression, the use of tourniquets and (non) commercial pelvic slings, and rapid transfer to an adequate trauma center. Upon hospital admission, coagulation monitoring and support are to be initiated immediately...

BACKGROUND/OBJECTIVE: There are limited data on the risks and benefits of using andexanet alfa (AA) in comparison with four-factor prothrombin complex concentrate (4F-PCC) to reverse factor Xa inhibitors (FXi) associated intracranial hemorrhage (ICH). We sought to describe our experience with AA or 4F-PCC in patients with oral FXi-related traumatic and spontaneous ICH. METHODS: We conducted a retrospective review of consecutive adult patients with FXi-related ICH who received AA or 4F-PCC...

BACKGROUND/OBJECTIVE: Intracranial bleeding (ICB) is a feared complication of systemic anticoagulation. Factor Xa inhibitors (FXaI) are used frequently due to their improved safety profile and predictable kinetics. Andexanet alfa was recently approved for emergent reversal of FXaI agents but was not compared formally to 4-Factor Prothrombin Complex Concentrates (4FPCC) which are the current standard of care in many centers. The objective of this study is to formally evaluate the hemostatic efficacy of 4FPCC in patients with FXaI-associated ICB...

BACKGROUND: Uncontrolled bleeding with trauma-induced coagulopathy (TIC) is still the most common avoidable cause of death in multiple trauma. The aging of the population has led to an increasing number of bleeding trauma patients with pre-existing anticoagulation. Such patients are not treated uniformly, even in major trauma centers. METHODS: This review is based on a selective search of the literature (Medline/PubMed, Cochrane Reviews) and summarizes current treatment recommendations, including those of the newly revised European trauma guidelines...

BACKGROUND: The prevalence of direct oral anticoagulants (DOACs) has increased with continued evidence of their efficacy and ease of use. However, the rise in their utilization also surfaced a concern regarding their reversal in patients actively bleeding and/or those requiring invasive procedures. Up until 2018, there were several reversal options available including 4-factor prothrombin complex concentrate (4-factor PCC), activated charcoal, desmopressin, and tranexamic acid. Then, in 2018, andexanet alpha, a recombinant factor Xa, was approved for the reversal of apixaban and rivaroxaban in patients with life-threatening or uncontrolled bleeding...

Andexanet-alpha is a specific reversal agent for direct factor Xa inhibitors (dFXaI). We aimed to project utilization rates and cost of andexanet for reversal of dFXaI-related major hemorrhage compared to 4-factor prothrombin complex concentrates (4F-PCC). A retrospective, multicenter review was conducted between 1/1/2014 and 7/15/2018 of patients who received 4F-PCC for reversal of dFXaI-related life-threatening hemorrhages. Total hospital reimbursements/patient were calculated based on national average MS-DRG payments adjusting for Medicare discounts...

Despite the widespread use of DOAC and recommendations of regulatory agencies and first consensus meetings on handling of bleeding situation under DOAC uncertainty still exists. In case of mild bleeding, the medical care of these patients and the delay of the next dose is advised. A laboratory analysis is indicated i. e. in case of known higher grade liver and kidney failure. The administration of factor concentrates or antidots is not indicated in this situation. In case of moderate to severe bleeding, the primary focus lies on stabilization of cardiopulmonary and circulatory function and parallel on the treatment depending on the localization of the bleeding source...

Oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) accounts for nearly 20% of all ICH. The number of patients with an indication for oral anticoagulant therapy (OAT) increases with increasing age. OAT became less complicate with the introduction of non-vitamin K oral anticoagulants (NOAC) OAT because of easier handling, favorable risk-benefit profile, reduced rates of ICH compared to vitamin K antagonists and no need for routine coagulation testing. Consequently, despite a better safety profile of NOAC the number of patients with OAC-ICH will increase...

Non-vitamin K oral anticoagulants (NOACs) are alternatives to vitamin K antagonists and provide consistent anticoagulation with equal or better clinical outcome and no need for routine monitoring. Bleeding is a feared complication of anticoagulants. Until recently, no specific agent has been available for reversal of NOACs. Idarucizumab binds dabigatran for rapid reversal of its activity without procoagulant effects. Andexanet alpha (expected release in 2016) and PER977 are antidotes under clinical development...

During the last 10 years, several novel direct oral anticoagulants (NOACs) have entered the clinical arena and were registered in the Russian Federation for use in patients presenting with atrial fibrillation, venous thrombosis, and pulmonary artery thromboembolism. NOACs are classified into two groups: direct thrombin inhibitor (notably dabigatran) and factor Xa inhibitors (including rivaroxaban, apixaban, and edoxaban). Their disadvantage is lack of specific antidotes in case of an emergency situation (injury, infarction, stroke requiring thrombolysis, urgent operation)...

For several decades the vitamin K antagonist oral anticoagulants were the only outpatient therapy that existed to reduce the risk of stroke and thromboembolism. When the new direct oral anticoagulants were approved for use and addressed many of the issues associated with oral vitamin K antagonists, a new concern arose-the lack of rapid ability to reverse these agents. Physicians and patients were concerned that in cases of life-threatening bleeding or need for emergent surgery, an antidote to reverse the anticoagulation effect of these agents did not exist...

Since 2009, four direct oral anticoagulants (DOACs) have been introduced for treatment of venous thromboembolism and stroke prevention in non-valvular atrial fibrillation. While they are currently first-line therapy for a majority of patients, there are a number of clinical situations where warfarin is preferable. In both randomised trials and real-world populations, use of DOACs significantly reduces the risk of intracranial haemorrhage as compared with warfarin. While drug-specific reversal agents are currently only available for dabigatran, andexanet alpha is pending approval for reversal of factor Xa inhibitors, reducing concerns about major bleeding for many patients and providers...

Direct oral anticoagulants (DOAC) are recommended for stroke prevention in atrial fibrillation and for the treatment of venous thromboembolism. However, they are associated with hemorrhagic complications. Management of DOAC-induced bleeding remains challenging. Activated or non-activated prothrombin concentrates are proposed, although their efficacy to reverse DOAC is uncertain. Therapeutic options also include antidotes: idarucizumab, antidote for dabigatran, has been approved for use whereas andexanet alpha, antidote for anti-Xa agents, and aripazine, antidote for all DOAC, are under development...

Target specific oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) are changing the landscape of anticoagulation. The major drawback is the absence of an effective antidote for severe bleedings and/or prior to procedures. Currently there are a few promising antidotes undergoing clinical trials. This review summarized the latest development in idarucizumab, andexanet alpha and PER977.