scholarly journals Idarucizumab for the treatment of dabigatran-related nephropathy

2020 ◽  
Author(s):  
Ammar Alsamarrai ◽  
Nicola Eaddy ◽  
Elizabeth Curry
Keyword(s):  
Acute Kidney Injury ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Specific Treatment ◽  
Kidney Injury ◽  
Clinical Syndrome ◽  
Reversal Agent ◽  
Macroscopic Haematuria ◽  
Anticoagulant Reversal

Abstract Anticoagulant-related nephropathy (ARN) is a clinical syndrome of acute kidney injury in patients taking vitamin K antagonists or direct oral anticoagulants. It is associated with increased mortality and there is no specific treatment. We report the case of a 78-year-old man on dabigatran who developed macroscopic haematuria and acute kidney injury 2 weeks after mitral valve repair, reaching a peak creatinine of 415 µmol/L from a normal baseline, which was successfully treated with one course of idarucizumab. This case illustrates the efficacy of an anticoagulant reversal agent for the treatment of ARN.

scholarly journals Applied Nanotechnologies in Anticoagulant Therapy: From Anticoagulants to Coagulation Test Performance of Drug Delivery Systems

Applied Nano ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 98-117
Author(s):  
Yuri B. G. Patriota ◽  
Luíse L. Chaves ◽  
Evren H. Gocke ◽  
Patricia Severino ◽  
Mônica F. R. Soares ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Anticoagulant Therapy ◽  
Test Performance ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Delivery Systems ◽  
Reversal Agent ◽  
Laboratory Assessment ◽  
Administration Routes

Heparin-based delivery systems have been explored to improve their therapeutic efficacy and to reduce toxicity for different administration routes. Regardless of the applied drug delivery system (DDS), the evaluation of anticoagulant performance is instrumental for the development of a suitable DDS. The understanding of the range of anticoagulant assays, together with their key applications and limitations, is essential both within the context of scientific research and for clinical usage. This review provides an overview of the current anticoagulant therapy and discusses the advantages and limitations of currently available anticoagulant assays. We also discuss studies involving low-molecular-weight heparin (LMWH)-based nanocarriers with emphasis on their anticoagulation performance. Conventional anticoagulants have been used for decades for the treatment of many diseases. Direct oral anticoagulants have overcome some limitations of heparins and vitamin K antagonists. However, the lack of an accurate laboratory assessment, as well as the lack of a factor “xaban” (Xa) inhibitor reversal agent, remains a major problem associated with these anticoagulants. LMWHs represent anticoagulant agents with noteworthy efficacy and safety, and they have been explored to improve their outcomes with various nanocarriers through several administration routes. The main problems related to LMWHs have been surmounted, and improved efficiency may be achieved through the use of DDSs.

scholarly journals Acute Kidney Injury due to Anticoagulant-Related Nephropathy : A Suggestion for Therapy

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Letizia Zeni ◽  
Chiara Manenti ◽  
Simona Fisogni ◽  
Vincenzo Terlizzi ◽  
Federica Verzeletti ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Kidney Injury ◽  
Cast Nephropathy ◽  
Anca Associated Vasculitis ◽  
A Prospective Study ◽  
The Relationship ◽  
Gross Haematuria ◽  
Strong Suspicion

The relationship between kidneys and anticoagulation is complex, especially after introduction of the direct oral anticoagulants (DOAC). It is recently growing evidence of an anticoagulant-related nephropathy (ARN), a form of acute kidney injury caused by excessive anticoagulation. The pathogenesis of kidney damage in this setting is multifactorial, and nowadays, there is no established treatment. We describe a case of ARN, admitted to our Nephrology Unit with a strong suspicion of ANCA-associated vasculitis due to gross haematuria and haemoptysis; the patient was being given dabigatran. Renal biopsy excluded ANCA-associated vasculitis and diagnosed a red blood cell cast nephropathy superimposed to an underlying IgA nephropathy. Several mechanisms are possibly responsible for kidney injury in ARN: tubular obstruction, cytotoxicity of heme-containing molecules and free iron, and activation of proinflammatory/profibrotic cytokines. Therefore, the patient was given a multilevel strategy of treatment. A combination of reversal of coagulopathy (i.e., withdrawal of dabigatran and infusion of its specific antidote) along with administration of fluids, sodium bicarbonate, steroids, and mannitol resulted in conservative management of AKI and fast recovery of renal function. This observation could suggest a prospective study aiming to find the best therapy of ARN.

Reversal strategies in patients treated with direct oral anticoagulants

VASA ◽  
2019 ◽  
Vol 48 (5) ◽  
pp. 389-392 ◽  
Author(s):  
Paul Gressenberger
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Invasive Procedure ◽  
Bleeding Risk ◽  
Study Data ◽  
Current Evidence ◽  
Bleeding Complications ◽  
Bleeding Events ◽  
Reversal Agent

Summary. Administration of direct oral anticoagulants (DOACs) for the treatment of venous thrombotic events (VTE) or non-valvular atrial fibrillation (AF) is now standard of care and has demonstrated clinical efficacy and safety in numerous clinical studies. Usually these substances have lower overall mortality and less risk of cerebral hemorrhage, but depending on the substance and study, they are more likely to cause gastrointestinal bleeding than vitamin K antagonists (VKA), the medication that used to be standard for VTE and AF. Since DOACs have very short plasma elimination half-lives compared to VKA, for most bleeding events, expert opinions suggest that withdrawal of DOACs and supportive care will likely suffice to stop a bleeding episode. Because there is a bleeding risk associated with DOACs, reversal strategies may be needed if a patient receiving DOAC therapy bleeds during surgery or an invasive procedure. So far, idarucizumab has been the only available antidote that binds specifically to dabigatran and safely and quickly reverses its anticoagulant effects. Idarucizumab has no effects on anti Xa inhibitors or other anticoagulants. To date, treatment of serious, life-threatening bleeds in patients with anti-Xa-inhibitor has involved 4 factor prothrombin complex concentrates (PCC). PCC restores normal hemostasis laboratory values in most patients with major bleeding events after anti Xa inhibitor intake. Recently, the US Food and Drug Administration (FDA) approved andexanet alfa as the first specific antidote for the anti-Xa inhibitors apixaban and rivaroxaban. So far clinical experience with this substance and data comparing it with PCC are lacking. Currently ciraparantag is under investigation as a universal reversal agent for all DOACs and low molecular weight heparin as well. Because it is so broadly applicable, ciraparantag might be a good future option for the management of most bleeding complications under anticoagulant treatment. The aim of this review is to summarize recent study data and recommendations on nonspecific and specific DOAC reversal strategies and to present the current evidence.

Anticoagulation and Reversal Agents

2018 ◽  
Author(s):  
Sarah Culbreth ◽  
Dirk Varelmann ◽  
Jessica Rimsans
Keyword(s):  
Vitamin K ◽  
Prothrombin Complex Concentrate ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Fresh Frozen Plasma ◽  
Reversal Agent ◽  
Reversal Agents ◽  
Fresh Frozen

Managing the balance between bleeding risk and the need to treat thromboembolic disease continues to challenge anesthesiologists and interventionalists, particularly as new direct oral anticoagulants (DOAC) are approved for use. While in the hospital, patients are often placed on parenteral anticoagulants that require monitoring to ensure the dynamic changes that occur in acute illness do not lead to excessive or insufficient anticoagulation. Until recently, vitamin K antagonists (VKA) have been the mainstay of therapy in patients with atrial fibrillation and venous thromboembolism. To facilitate procedures and or minimize bleeding, VKAs were either held or its effects reversed by vitamin K, fresh frozen plasma, or four-factor prothrombin complex concentrate to facilitate procedures and minimize bleeding. Those patients on DOACs continue to challenge the interventionist as there is no commercially available targeted reversal agent for all DOACs. When anticoagulation reversal is warranted, timing or urgency of reversal, the mechanism of action of the anticoagulant, half-life of the anticoagulant, risk of bleeding associated with the procedure, end-organ function, and the patient’s risk factors for thrombosis and bleeding should be considered. This chapter briefly reviews anticoagulants and reversal strategies. This review contains 1 figure, 10 tables, and 53 references. Key Word: activated prothrombin complex concentrate, anticoagulation, antithrombotic, life-threatening bleeding, reversal, periprocedural, prothrombin complex concentrate, surgery

Andexanet Alfa, the Possible Alternative to Protamine for Reversal of Unfractionated Heparin

2020 ◽  
Vol 55 (2) ◽  
pp. 261-264
Author(s):  
John N. Maneno ◽  
Genevieve Lynn Ness
Keyword(s):  
Unfractionated Heparin ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Hospital Setting ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Thrombin Time ◽  
Reversal Agent

The recent shortage of protamine prompted an investigation of alternatives for reversal of unfractionated heparin. Heparin is an anticoagulant utilized in the hospital setting. Available options for anticoagulation include direct oral anticoagulants, vitamin K antagonists, thrombin inhibitors, low-molecular-weight heparins, and heparin. Protamine is the approved reversal agent for heparin with few alternatives under investigation. Although andexanet was designed as an antidote for apixaban and rivaroxaban, in vitro studies show that in a dose-dependent technique, andexanet had near full reversal of heparin, reversed anti–factor Xa activity, and neutralized anticoagulant effects of activated partial thromboplastin time and thrombin time induced by heparin.

scholarly journals Direct Oral Anticoagulants and Risk of Acute Kidney Injury in Patients With Atrial Fibrillation

2018 ◽  
Vol 71 (2) ◽  
pp. 251-252 ◽  
Author(s):  
Jung-Im Shin ◽  
Shengyuan Luo ◽  
G. Caleb Alexander ◽  
Lesley A. Inker ◽  
Josef Coresh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Acute Kidney Injury ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Kidney Injury

Ciraparantag, an Anticoagulant Reversal Drug: Mechanism of Action, Pharmacokinetics and Reversal of Anticoagulants

Blood ◽  
2020 ◽  
Author(s):  
Jack Ansell ◽  
Bryan Laulicht ◽  
Sasha H Bakhru ◽  
Allison Burnett ◽  
Xuan Jiang ◽  
...  
Keyword(s):  
Animal Models ◽  
Blood Loss ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Coagulation Factors ◽  
Reversal Agent ◽  
Binding Characteristics ◽  
Drug Mechanism ◽  
Anticoagulant Reversal ◽  
Charge Interaction

Ciraparantag, an anticoagulant reversal agent, is a small molecule specifically designed to bind non-covalently by charge-charge interaction to unfractionated heparin (UFH) and low molecular weight heparin (LMWH). It shows similar binding characteristics to the direct oral anticoagulants (DOAC). Dynamic light scattering methodology was used to demonstrate ciraparantag binding to the heparins and DOACs and its lack of binding to a variety of proteins including coagulation factors and to commonly used drugs. Ciraparantag reaches maximum concentration within minutes following intravenous (IV) administration with a half-life of 12 - 19 minutes. It is primarily hydrolyzed by serum peptidases into two metabolites, neither of which has substantial activity. Ciraparantag and its metabolites are recovered almost entirely in the urine. In animal models of bleeding (rat tail transection and liver laceration) a single IV dose of ciraparantag given at peak concentrations of the anticoagulant, but before the bleeding injury, significantly reduces the amount of blood loss. Ciraparantag given after the bleeding injury also significantly reduces blood loss. Ciraparantag appears to have substantial ability to reduce blood loss in animal models given a variety of anticoagulants and has potential as a useful DOAC reversal agent.

Perioperative Management of Patients Receiving New Anticoagulants

2019 ◽  
Vol 25 (19) ◽  
pp. 2149-2157 ◽  
Author(s):  
Massimo Lamperti ◽  
Andrey Khozenko ◽  
Arun Kumar
Keyword(s):  
Vitamin K ◽  
Elective Surgery ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Oral Intake ◽  
Bleeding Risk ◽  
Dietary Vitamin ◽  
Reversal Agent ◽  
Onset Of Action ◽  
Reversal Agents

There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitamin K intake. New non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. Their management is easier as it requires a fixed daily dose without coagulation monitoring. Although their therapeutic profile is safe, proper attention should be paid in case of unexpected need for the reversal of their coagulation effect and in case a patient needs to have a scheduled surgery. For non-acute cardiac surgery, discontinuation of NOACs should start at least 48 hours prior surgery. Intracranial bleedings associated with NOACs are less dangerous comparing to those warfarin-induced. NOACs need to be stopped ≥24 hours in case of elective surgery for low bleeding-risk procedures and ≥48 hours for high bleeding-risk surgery in patients with normal renal function and 72 hours in case of reduced CrCl < 80. The therapy with NOACs should be resumed from 48 to 72 hours after the procedure depending on the perceived bleeding, type of surgery and thrombotic risks. There are some available NOAC reversal agents acting within 5 to 20 minutes. In case of lack of reversal agent, adequate diuresis, renal replacement therapy and activated charcoal in case of recent ingestion should be considered.

scholarly journals Determinants of Outcomes of Acute Kidney Injury: Clinical Predictors and Beyond

2021 ◽  
Vol 10 (6) ◽  
pp. 1175
Author(s):  
Emaad M. Abdel-Rahman ◽  
Faruk Turgut ◽  
Jitendra K. Gautam ◽  
Samir C. Gautam
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Complete Recovery ◽  
Severe Form ◽  
Clinical Syndrome ◽  
Current Evidence ◽  
Clinical Predictors ◽  
End Stage

Acute kidney injury (AKI) is a common clinical syndrome characterized by rapid impairment of kidney function. The incidence of AKI and its severe form AKI requiring dialysis (AKI-D) has been increasing over the years. AKI etiology may be multifactorial and is substantially associated with increased morbidity and mortality. The outcome of AKI-D can vary from partial or complete recovery to transitioning to chronic kidney disease, end stage kidney disease, or even death. Predicting outcomes of patients with AKI is crucial as it may allow clinicians to guide policy regarding adequate management of this problem and offer the best long-term options to their patients in advance. In this manuscript, we will review the current evidence regarding the determinants of AKI outcomes, focusing on AKI-D.

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