Antidote for dabigatran

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...

: Ibrutinib is the first clinically approved inhibitor of Bruton's tyrosine kinase, an essential enzyme for survival and proliferation of B cells by activating the B-cell receptor-signalling pathway. Ibrutinib has been shown to be highly effective in B-cell malignancies and is recommended in current international guidelines as a first-line and/or second-line treatment of chronic lymphocytic leukemia. The drug has a favorable tolerability and safety profile but the occurrence of specific side effects (e.g. atrial fibrillation, bleeding and hypertension)...

INTRODUCTION: Direct thrombin inhibitor, dabigatran and factor Xa inhibitors, apixaban, edoxaban, and rivaroxaban (DOACs/NOACs), are currently the first-choice drugs in some indications. Life-threatening bleeding occurring during DOACs treatment may benefit from the use of reversal agents, however there are some concerns regarding potential rebound thrombotic events. In this systematic review we aimed to estimate the incidence of thrombotic events in patients treated with idarucizumab or andexanet alfa...

Direct oral anticoagulants (DOACs), among them dabigatran, have a favorable benefit-risk profile compared with warfarin, and no monitoring of the anticoagulant effect is required. However, reversing the anticoagulant effect immediately is very useful in cases of life-threatening bleeding and emergency surgical procedure requirement. Idarucizumab, a humanized monoclonal antibody fragment, is currently the only reversal agent of a DOAC available in Argentina. Idarucizumab immediately reverse the effect of dabigatran...

Patients on anticoagulant therapy for the prevention of cardiovascular accidents present an increased risk of bleeding following dental and oral surgery. Four recently introduced non-vitamin K antagonist oral anticoagulants, namely dabigatran etexilate (direct thrombin inhibitor), rivaroxaban, apixaban, and edoxaban (Xa factor direct inhibitor), are widely spreading for convenience of use compared to the older drug class. Dental management of patients taking these drugs has substantial differences compared to patients on vitamin K antagonist therapy...

The direct oral anticoagulants targeting coagulation factor Xa or thrombin are widely used as alternatives to vitamin K antagonists in the management of venous thromboembolism and nonvalvular atrial fibrillation. In case of bleeding or emergency surgery, reversal agents are helpful to counteract the anticoagulant therapy and restore hemostasis. While idarucizumab has been established as an antidote for the direct thrombin inhibitor dabigatran, reversal strategies for the direct factor Xa inhibitors have been a focal point in clinical care over the past years...

BACKGROUND: Major bleeding is a life-threatening condition and a medical emergency with high mortality risk. It is often the complication of anticoagulant's intake. Anticoagulants are commonly used for the prevention and treatment of thrombotic events. The standard therapy with vitamin K antagonist (warfarin) has been frequently replaced by direct oral anticoagulants (DOACs). The latter agents (rivaroxaban, apixaban, edoxaban, dabigatran, and betrixaban) showed better efficacy and safety compared to standard warfarin treatment and they are recommended for the reduction of ischemic stroke...

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...

The number of patients treated with direct oral anticoagulants is increasing worldwide. Although bleeding complications associated with direct oral anticoagulants are lower than those associated with vitamin K antagonists, the increased number of patients treated with these anticoagulants suggests that a higher absolute number of patients are at risk. Tube thoracostomy is an invasive procedure with a high risk of bleeding. To date, among direct oral anticoagulants, only dabigatran has a well-studied antidote to reverse its effects during emergency procedure or surgery...

Background: The residual antithrombotic activity 12 hours after intake of direct oral anticoagulants (DOACs) is of clinical relevance in the setting of bleeding or urgent surgery. Objective: To evaluate the effects of DOACs on thrombin generation 12 hours after DOAC intake in comparison to baseline and a healthy control group. Methods: Eighty patients were recruited, 20 patients for each approved DOAC: apixaban, edoxaban, rivaroxaban, and dabigatran...

BACKGROUND: Individuals on anticoagulation therapy are at increased risk of bleeding, including epistaxis. There is a lack of available reversal agents for novel oral anticoagulation therapy. OBJECTIVE: This paper reviews the current literature on epistaxis in the context of novel oral anticoagulation use, in order to recommend guidelines on management. METHOD: A comprehensive search of published literature was conducted to identify all relevant articles published up to April 2019...

BACKGROUND: Real-life experience with idarucizumab, which reverses the anticoagulant effect of dabigatran, is currently limited. OBJECTIVE: To evaluate efficacy and safety of the clinical use of idarucizumab after its availability in Slovenia. METHODS: We analysed consecutive cases treated with idarucizumab in Slovenia from January to October 2016. The decision to reverse dabigatran with idarucizumab was made by the treating clinicians, as was the assessment of clinical outcomes and blood sampling/monitoring (activated partial thromboplastin time, thrombin time and diluted thrombin time) before and after use...

BACKGROUND: Idarucizumab is a specific antidote for the anticoagulant dabigatran. Although its efficacy has been recently reported, the drug is still in postmarketing surveillance and requires case data in different emergency settings. A newer intravenous thrombolytic therapy with recombinant tissue plasminogen activator has been proposed after injection of idarucizumab in patients receiving dabigatran; however, the safety and efficacy of this therapy are equivocal because of the limited number of reported cases...

Uninterrupted anticoagulation therapy during atrial fibrillation (AF) ablation minimizes the risk of periprocedural thromboembolic events. Although the use of direct oral anticoagulants (DOACs) has rapidly developed in patients undergoing AF ablation, no antidote is available for factor Xa inhibitors. We sought to investigate the feasibility of an uninterrupted DOAC protocol with temporary switching to dabigatran ("dabigatran bridge") for AF ablation.The study consisted of consecutive 137 patients in whom DOACs were interrupted on the procedural day with heparin bridging (interrupted group) and 135 in whom DOACs were uninterrupted with temporary switching to dabigatran during the periprocedural hospitalization period ("dabigatran bridge" group)...

BACKGROUND: Idarucizumab is a humanized, monoclonal antibody fragment used specifically to reverse the anticoagulant effects of dabigatran. CASE REPORTS: We discuss 4 cases of patients who were treated with idarucizumab to reverse dabigatran before early/emergency surgery. Two of the patients had subdural hematomas, 1 had a splenic laceration, and 1 had Fournier gangrene. All patients received 5 g of idarucizumab before surgery. Intraoperative blood loss in all patients was normal, no adverse events were reported, and the patients recovered normally...

The main advantage of the direct oral anticoagulants over vitamin K antagonists is reduced rates of major bleeding, especially intracranial hemorrhage. While use of different clotting factor supplements have been used in patients with direct oral anticoagulant induced major bleeding or when there is need for urgent surgery, the lack of preclinical and clinical data are concerning. Idarucizumab is a specific antibody developed with a 350-fold greater affinity for dabigatran than its pharmacologic target thrombin...

BACKGROUND : Direct oral anticoagulants (DOAC) are an attractive alternative over vitamin K antagonists. They have several advantages in primary and secondary prevention of thromboembolisms due to atrial fibrillation, as well as in prevention and treatment of thromboembolic venous disease. They have fast onset action, do not need laboratory controls in patients with normal renal function, and they have practically no interference with the patient's diet or medications. The strongest objection to their use was the lack of reversal agents that could be used in case of life-threatening haemorrhage or the need for emergency surgery...

PURPOSE: A case report of dabigatran-associated coagulopathy that lasted for about 1 week after drug discontinuation despite use of several treatment measures is presented. SUMMARY: Life-threatening hemorrhage can occur in patients receiving dabigatran, a direct-acting oral anticoagulant. Idarucizumab is a newly approved dabigatran antidote that neutralizes the drug's anticoagulant activity. An 80-year-old Caucasian man with a medical history of hypertension, coronary artery disease, congestive heart failure, gout, and atrial fibrillation was hospitalized with acute kidney injury (AKI) caused by bilateral hydronephrosis secondary to distal urethral stricture...

BACKGROUND: The Redual PCI trial has demonstrated the safety of dabigatran and ticagrelor or clopidogrel combination in preventing strokes in patients with atrial fibrillation. There was 15.4% risk of hemorrhage in the dabigatran/ticagrelor or clopidrogel arm, lower than that of triple therapy with warfarin, aspirin and ticagrelor or clopidogrel. While idarucizumab is an effective antidote for dabigatran, there is no good method for antagonizing both dabigatran and ticagrelor. We tested in this study a hemadsorbtion method for removing dabigatran that we had previously successfully applied in the removal of ticagrelor from human blood...

In light of an aging population with increased cardiovascular comorbidity, the use of oral anticoagulation (OAC) is steadily expanding. A variety of pharmacological alternatives to vitamin K antagonists (VKA) have emerged over recent years (direct oral anticoagulants, DOAC, i.e., dabigatran, rivaroxaban, apixaban, and edoxaban) which show a reduced risk for the occurrence of intracerebral hemorrhage (ICH). Yet, in the event of ICH under OAC (OAC-ICH), hematoma characteristics are similarly severe and clinical outcomes likewise substantially limited in both patients with VKA- and DOAC-ICH, which is why optimal acute hemostatic treatment in all OAC-ICH needs to be guaranteed...