scholarly journals Utilization of anti–factor Xa levels to guide reversal of oral factor Xa inhibitors in the emergency department

2021 ◽  
Author(s):  
Anne E Zepeski ◽  
Brett A Faine ◽  
Anna E Merrill ◽  
Grerk Sutamtewagul ◽  
Sharathkumar Bhagavathi
Keyword(s):  
Emergency Department ◽  
Anticoagulation Therapy ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Prothrombin Complex Concentrates ◽  
Anticoagulation Reversal ◽  
Reversal Agents ◽  
Patient Disposition ◽  
Rule Out

Abstract Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Oral factor Xa inhibitors (FXaIs) are increasingly utilized for outpatient anticoagulation therapy; however, laboratory monitoring is not routinely used to assess the safety and efficacy of these agents. We aimed to evaluate the role of chromogenic anti–factor Xa (anti-Xa) assays in the emergency department (ED) in the setting of patients with an acute bleed or requiring emergent procedures. Methods A retrospective review was completed of anti-Xa levels obtained in the ED between June 1, 2019, and April 30, 2020. Data were collected to describe the clinical setting of anti-Xa level collection, oral FXaIs used before admission, administration of reversal agents, and patient disposition to further characterize the role of anti-Xa levels in the management of rivaroxaban and apixaban reversal. Results Thirty anti-Xa levels were included in the final analysis. The median time from sample collection to anti-Xa assay result was 45.9 minutes (interquartile range, 35.3-54.7 minutes). Eleven patients (37%) received anticoagulation reversal after their anti-Xa levels were determined. Anticoagulation reversal agents included either activated prothrombin complex concentrates (aPCCs) or prothrombin complex concentrates (PCCs). Anti-Xa levels were collected in 2 patients who had received PCCs before arrival at our ED. Of the patients with anti-Xa levels below 30 ng/mL, none received aPCCs or PCCs after their anti-Xa levels were determined. Anti-Xa assays were used to rule out the presence of FXaIs in 3 patients. Conclusion This study illustrates the novel role of anti-Xa levels in managing patients with an emergent need for reversal in the ED. The assay may be used to rule out the presence of oral FXaIs and avoid unnecessary administrations of anticoagulation reversal agents.

scholarly journals Role of Factor Xa Inhibitors in Cancer-Associated Thrombosis: Any New Data?

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Ali Zalpour ◽  
Michael H. Kroll ◽  
Vahid Afshar-Kharghan ◽  
Syed Wamique Yusuf ◽  
Carmen Escalante
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Anticoagulation Therapy ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
The Us ◽  
Prevention And Treatment ◽  
Cancer Associated Thrombosis ◽  
Current Guidelines

The association between cancer and venous thromboembolism (VTE) has been well documented in the literature. Prevention and treatment of VTE in cancer patients is imperative. Typically, the mainstay regimen for VTE prevention and treatment has been anticoagulation therapy, unless contraindicated. This therapy consists of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), factor Xa inhibitor, or vitamin K antagonist (VKA). Current guidelines recommend LMWH over VKA for the treatment of VTE in cancer patients. Factor-specific anticoagulants have been proven safe and effective, and recently factor Xa inhibitors have emerged as a treatment alternative to heparins and VKA. Currently, three factor Xa inhibitors have been identified: fondaparinux (the only one approved so far by the US Food and Drug Administration), idraparinux (in clinical trials), and idrabiotaparinux (in clinical trials). This paper will examine the role of these agents, focusing on fondaparinux, for the prevention and treatment of VTE in cancer patients.

scholarly journals Clinical Course of Intracranial Bleeding in Patients Anticoagulated With Factor Xa inhibitors Without the Use of Specific Reversal Agents

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Emmalin Nelton ◽  
Georgios Maragkos ◽  
Sven Richter ◽  
Aristotelis Filippidis ◽  
Martina Stippler
Keyword(s):  
Clinical Outcomes ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Secondary Outcome ◽  
Primary Study ◽  
Reversal Agent ◽  
Anticoagulation Reversal ◽  
Reversal Agents ◽  
Traumatic Intracranial Hemorrhage ◽  
History Of

Abstract INTRODUCTION Factor Xa inhibitors (FXI) are widely used anticoagulants but may cause or worsen acute major bleeding. Andexanet alfa, a novel anticoagulation reversal agent for FXI, was recently approved. Traumatic intracranial hemorrhage (tICH) presents a prime target for this drug, however questions remain regarding its effect on clinical outcomes compared to the natural history of tICH in the setting of FXI. This study aimed to evaluate the hematoma progression and clinical outcomes of patients on FXI who were not administered Andexanet reversal after tICH. METHODS An institutional traumatic brain injury (TBI) registry was queried between 2016 and 2019. Patients with recorded use of apixaban or rivaroxaban <18 h before injury were included. The primary study outcome was good hemostasis on repeated head computed tomography (CT), assessed according to the criteria of the ANNEXA-4 trial for Andexanet treatment. The secondary outcome was neurological worsening or surgical intervention during the hospitalization. RESULTS We identified 24 patients meeting the study inclusion criteria. Their mean (SD) age was 76.3 ± 13 yr and 10 (42%) were female. On admission CT, 15 patients had SDH, 6 had traumatic IPH, and 3 had SAH. All patients had their FXI therapy discontinued immediately after injury. Anticoagulation reversal was attempted in 16 patients, most commonly using prothrombin complex concentrate (PCC). Out of the 24 patients, 19 (79%) were adjudicated as having excellent or good hemostasis. A total of 23 (96%) patients remained neurologically stable throughout admission. CONCLUSION Our results indicate that in patients on FXI with complicated mild TBI it can be reasonably safe not to administer specific anticoagulation reversal. Hemostatic and clinical outcomes in our cohort were largely similar to those reported after Andexanet administration. Further research is necessary to determine if administration of Andexanet improves clinical outcomes.

scholarly journals Reversing targeted oral anticoagulants

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 518-523 ◽  
Author(s):  
Maureane Hoffman ◽  
Dougald M. Monroe
Keyword(s):  
Factor Viia ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Novel Oral Anticoagulants ◽  
Factor Xa Inhibitors ◽  
Invasive Procedures ◽  
Prothrombin Complex Concentrates ◽  
Reversal Agents ◽  
Life Threatening ◽  
Orally Active

Abstract Dabigatran, rivaroxaban, and apixaban are orally active anticoagulants that are approved in many countries. Dabigatran inhibits thrombin, whereas rivaroxaban and apixaban are factor Xa inhibitors. In clinical trials, these novel oral anticoagulants were at least as effective as warfarin for preventing stroke in patients with atrial fibrillation, but with a lower rate of serious bleeding. However, the lack of true antidotes for these agents has caused concern when patients suffer life-threatening bleeding or trauma or require emergent invasive procedures. True antidotes are under development for all of these agents. In the meantime, activated and nonactivated prothrombin complex concentrates have been used as reversal agents. Factor VIIa may also be effective for reversal of the factor Xa inhibitors. Reversal of novel oral anticoagulants by these hemostatic agents has not been studied in bleeding human patients, so their true efficacy and appropriate dosing are not known.

Heparin induced thrombocytopenia

2015 ◽  
Vol 35 (04) ◽  
pp. 372-375 ◽  
Author(s):  
N. A. Viniou ◽  
P. Diamantopoulos ◽  
J. Barbetseas ◽  
E. A. Sanidas
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Options ◽  
Factor Xa ◽  
Additional Treatment ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Clinical Aspects ◽  
Heparin Induced Thrombocytopenia

SummaryHeparin induced thrombocytopenia (HIT) is a prothrombotic syndrome initiated by platelet-activating auto-antibodies with potentially devastating complications. Once the diagnosis of HIT is suspected, discontinuation of heparin and treatment with an alternative anticoagulant are mandatory. While established drugs for HIT are no longer available, parenteral factor Xa inhibitors, thrombin inhibitors and perhaps the direct oral anticoagulants provide additional treatment options. The aim of this review was to highlight the current clinical aspects regarding HIT focusing on the role of novel medications.

scholarly journals Reversal of direct oral anticoagulants: a practical approach

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 612-619 ◽  
Author(s):  
Andrew W. Shih ◽  
Mark A. Crowther
Keyword(s):  
Phase 1 ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Antibody Fragment ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Severe Bleeding ◽  
Thrombin Time ◽  
Ancillary Benefits ◽  
Reversal Agents

Abstract Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered. Laboratory testing has limited utility in the acute management of bleeding; thrombin time and activated partial thromboplastin time may be useful for excluding clinically relevant levels of dabigatran. Prothrombin time is potentially useful for rivaroxaban and edoxaban, but calibrated anti-Xa assays are optimal for determining clinically relevant levels of factor Xa inhibitors. Because specific reversal agents are not widely available, supportive care and interventions for local hemostasis remain the cornerstones of therapy in the patient with DOAC-associated bleeding. Nonspecific reversal agents should be considered only in the event of severe bleeding because their efficacy is unknown, and they are associated with risk of thrombosis. Recent results from phase 3/4 studies demonstrate efficacy for an antidote to dabigatran (idarucizumab, a monoclonal antibody fragment with specificity for dabigatran) and an antidote to factor Xa inhibitors (andexanet alfa, a recombinant and inactive form of factor Xa that binds inhibitors). A universal reversal agent (ciraparantag) for many anticoagulants, including the DOACs, shows promise in results from phase 1 and 2 studies.

scholarly journals Monitoring and reversal of direct oral anticoagulants

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 117-124 ◽  
Author(s):  
Adam Cuker ◽  
Deborah Siegal
Keyword(s):  
Prothrombin Complex Concentrate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Antibody Fragment ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Severe Bleeding ◽  
Thrombin Time ◽  
Reversal Agents ◽  
Routine Monitoring

Abstract Although the direct oral anticoagulants (DOACs) do not require routine monitoring and reduce bleeding compared with warfarin, there are special circumstances in which laboratory measurement or reversal of their anticoagulant effect may be indicated. The dilute thrombin time and ecarin-based assays are able to quantify dabigatran across a broad range of concentrations, but are not widely available. A normal thrombin time excludes clinically relevant levels and a normal activated partial thromboplastin time probably excludes excess levels of dabigatran. Factor Xa inhibitors may be quantified with an anti-Xa assay calibrated with drug-specific standards. A normal prothrombin time probably excludes excess levels of rivaroxaban and edoxaban, but not apixaban. Patients with minor and moderate DOAC-associated bleeding can be treated with supportive care and general hemostatic measures. Nonspecific reversal agents (eg, prothrombin complex concentrate, activated prothrombin complex concentrate) are of unproven benefit, carry a risk of thrombosis, and should be reserved for severe bleeding. Specific reversal agents, such as idarucizumab (a monoclonal antibody fragment that binds dabigatran) and andexanet alfa (a recombinant factor Xa variant that binds factor Xa inhibitors but lacks coagulant activity), are in clinical development.

Monitoring and reversal of direct oral anticoagulants

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 117-124 ◽  
Author(s):  
Adam Cuker ◽  
Deborah Siegal
Keyword(s):  
Prothrombin Complex Concentrate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Antibody Fragment ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Severe Bleeding ◽  
Thrombin Time ◽  
Reversal Agents ◽  
Routine Monitoring

Although the direct oral anticoagulants (DOACs) do not require routine monitoring and reduce bleeding compared with warfarin, there are special circumstances in which laboratory measurement or reversal of their anticoagulant effect may be indicated. The dilute thrombin time and ecarin-based assays are able to quantify dabigatran across a broad range of concentrations, but are not widely available. A normal thrombin time excludes clinically relevant levels and a normal activated partial thromboplastin time probably excludes excess levels of dabigatran. Factor Xa inhibitors may be quantified with an anti-Xa assay calibrated with drug-specific standards. A normal prothrombin time probably excludes excess levels of rivaroxaban and edoxaban, but not apixaban. Patients with minor and moderate DOAC-associated bleeding can be treated with supportive care and general hemostatic measures. Nonspecific reversal agents (eg, prothrombin complex concentrate, activated prothrombin complex concentrate) are of unproven benefit, carry a risk of thrombosis, and should be reserved for severe bleeding. Specific reversal agents, such as idarucizumab (a monoclonal antibody fragment that binds dabigatran) and andexanet alfa (a recombinant factor Xa variant that binds factor Xa inhibitors but lacks coagulant activity), are in clinical development.

Anticoagulation Therapy. Heparins, Factor II and Factor Xa Inhibitors

2013 ◽  
pp. 59-122
Author(s):  
Ana Muñiz-Lozano ◽  
Fabiana Rollini ◽  
Francesco Franchi ◽  
Dominick J. Angiolillo
Keyword(s):  
Anticoagulation Therapy ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Factor Ii
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