scholarly journals Direct oral anticoagulants; a review for the non-specialist

2021 ◽  
Vol 13 (4) ◽  
Author(s):  
Thilina Gunawardena

Thrombin inhibitors and direct factor Xa inhibitors represent a major breakthrough in the field of anticoagulation pharmacotherapy. These novel agents have replaced warfarin as the oral anticoagulant of choice in certain indications, as they possess equal or superior efficacy and better safety profiles. They have a quick onset of action, predictable pharmacokinetic properties and minimal drug and food interactions. So they do not require frequent blood monitoring and dose adjustments as with warfarin. Considering all the advantages, there seems to be a rapid increase in the number of patients who are started on these novel anticoagulants. In this review, we highlight the pharmacology of these direct oral anticoagulants and the evidence-based indications for their use. We aim to provide a clinical overview for the non-specialist who may be called upon to manage a patient who is currently on one of these novel anticoagulants.

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 129-133
Author(s):  
Karen A. Moser ◽  
Kristi J. Smock

Abstract Direct oral anticoagulants (DOACs) are a group of direct coagulation factor inhibitors including both direct thrombin inhibitors and direct factor Xa inhibitors. These medications may cause hemostasis assay interference by falsely increasing or decreasing measured values, depending on the analyte. Considering the potential for DOAC interference in a variety of hemostasis assays is essential to avoid erroneous interpretation of results. Preanalytic strategies to avoid DOAC interference include selecting alternatives to clot-based hemostasis assays in patients taking DOACs when possible and sample collection timed when the patient is off anticoagulant therapy or at the expected drug trough. Clinical laboratories may also provide educational materials that clearly describe possible interferences from DOAC, develop testing algorithms to aid in detection of DOAC in submitted samples, use DOAC-neutralizing agents to remove DOACs before continuing with testing, and write interpretive comments that explain the effects of DOAC interference in hemostasis tests. Using a combination of the described strategies will aid physicians and laboratorians in correctly interpreting hemostasis and thrombosis laboratory tests in the presence of DOACs.


2015 ◽  
Vol 35 (04) ◽  
pp. 372-375 ◽  
Author(s):  
N. A. Viniou ◽  
P. Diamantopoulos ◽  
J. Barbetseas ◽  
E. A. Sanidas

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.


2020 ◽  
Vol 48 (6) ◽  
pp. 030006051989443
Author(s):  
Priya Bhardwaj ◽  
Louise Breum Petersen ◽  
Tomas Sorm Binko ◽  
Jan Roland Petersen ◽  
Gitte Gleerup Fornitz

Introduction Patients treated with direct oral anticoagulants (DOACs) are at increased bleeding risk. It is therefore of increasing interest to identify predictors of bleeding episodes to increase safety during treatment with DOACs. Methods This retrospective cohort study systematically reviewed medical records of 235 patients treated with either apixaban, rivaroxaban or dabigatran for non-valvular atrial fibrillation or venous thromboembolism and collected data on the international normalized ratio (INR) and all bleeding episodes. Results INR ≥ 1.5 was significantly associated with increased risk of minor and major bleeding events in patients treated with direct factor Xa inhibitors. This association was not present in patients treated with dabigatran. However, a high negative predictive value was identified for INR < 1.5 for all drugs. The relative risks of bleeding episodes in patients with INR ≥ 1.5 and INR < 1.5 were 5.1 and 0.20, respectively. Conclusions Our results demonstrate a strong correlation between INR and risk of bleeding episodes during DOAC treatment. INR < 1.5 was a strong negative predictor for low bleeding risk independent of indication or choice of drug, and INR ≥ 1.5 was associated with increased risk of bleeding episodes in patients treated with direct factor Xa-inhibitors.


2018 ◽  
Vol 118 (09) ◽  
pp. 1535-1544 ◽  
Author(s):  
Georges Jourdi ◽  
Isabelle Gouin-Thibault ◽  
Virginie Siguret ◽  
Sophie Gandrille ◽  
Pascale Gaussem ◽  
...  

Increasing number of patients are treated with direct oral anticoagulants (DOAC). An antidote for dabigatran inhibiting thrombin (idarucizumab) is available but no antidote is yet approved for the factor Xa (FXa) inhibitors (xabans). We hypothesized that a complex between Gla-domainless FXa and α2-macroglobulin (GDFXa-α2M) may neutralize the xabans without interfering with normal blood coagulation.Purified α2M was incubated with GDFXa to form GDFXa-α2M. Affinity of apixaban and rivaroxaban for GDFXa-α2M was only slightly decreased compared to FXa. Efficacy and harmlessness of GDFXa-α2M were tested in vitro and in vivo. Stoichiometric excess of GDFXa-α2M neutralized rivaroxaban and apixaban as attested by clot waveform assay and rotational thromboelastometry, whereas GDFXa-α2M alone had no effect on these assays. Efficacy and pro-thrombotic potential of GDFXa-α2M were also assessed in vivo. Half-life of GDFXa-α2M in C57BL6 mice was 4.9 ± 1.1 minutes, but a 0.5 mg/mouse dose resulted in uptake saturation such that 50% persistence was still observed after 170 minutes. Single administration of GDFXa-α2M significantly decreased the rivaroxaban-induced bleeding time (p < 0.001) and blood loss (p < 0.01). GDFXa-α2M did not increase D-dimer or thrombin–antithrombin complex formation, suggesting a lack of pro-thrombotic potential.GDFXa-α2M is therefore an attractive candidate for xaban neutralization neither pro- nor anticoagulant in vitro as well as in vivo.


Author(s):  
Н.А. Воробьева ◽  
Е.Ю. Мельничук ◽  
А.И. Воробьева

Введение. Для пролонгированной профилактики тромбозов после операций, при фибрилляции предсердий, терапии тромбозов глубоких вен и/или тромбоэмболии легочной артерии широко используются прямые пероральные антикоагулянтные препараты (ПОАК). Считается, что ПОАК лишены недостатков, присущих антагонистам витамина К (АВК) и обладают предсказуемыми фармакокинетическими и фармакодинамическими эффектами и следовательно не требуют рутинного лабораторного контроля для коррекции и подбора дозы препарата. Отдельного внимания, на наш взгляд, заслуживает вопрос приверженности к терапии ПОАК. Цель исследования: оценка приверженности к терапии прямыми пероральными ингибиторами фактора Ха путем определения концентрации ПОАК в плазме крови пациентов. Материалы и методы. Выполнено проспективное клинико-лабораторное исследование, включены 50 пациентов с продленной антитромботической терапией ПОАК. Для оценки приверженности к терапии проведено определение пиковой концентрации прямых ингибиторов фактора Ха хромогенным методом. Результаты. До 10% пациентов в реальной клинической практике не принимали назначенную антитромботическую терапию и скрыли этот факт от врача. Таким образом, с помощью определения концентрации прямых ингибиторов фактора Ха хромогенным методом можно выявить отсутствие приверженности к терапии ПОАК. Заключение. Для определения приверженности к антикоагулянтной терапии прямыми ингибиторами фактора Ха возможно использование метода оценки концентрации ПОАК в плазме крови, что позволяет оценить приверженность пациента к данному виду терапии и, как следствие, эффективность и безопасность продленной антитромботической терапии. Background. For prolonged prophylaxis of thrombosis after surgery, of atrial fibrillation, therapy of deep vein thrombosis and/or pulmonary embolism, direct oral anticoagulants (DOACs) are widely used. It is believed that DOACs lack the deficiencies inherent in antagonists of vitamin K (AVK), have predictable pharmacokinetic and pharmacodynamic effects, and therefore do notrequire routine laboratory monitoring to adjust and select the dose of the drug. We pay special attention to the issue of adherence to DOACs therapy. Objectives: to assess compliance to therapy with direct oral factor Xa inhibitors by determining plasma DOACs concentration. Patients/Methods. A prospective clinical and laboratory study was performed, 50 patients with prolonged antithrombotic therapy by DOACs were included. To assess compliance to therapy, the peak concentration of direct factor Xa inhibitors was determined by the chromogenic method. Results. In real clinical practice up to 10% of patients did not take the prescribed antithrombotic therapy and hid this fact from the doctor. Thus, by determining the concentration of direct factor Xa inhibitors by the chromogenic method, it is possible to identify a lack of compliance to therapy. Conclusions. Determination of plasma DOACs concentration allows assessing the patient’s adherence to anticoagulant therapy with direct factor Xa inhibitors and the efficacy and safety of prolonged antithrombotic therapy.


2016 ◽  
Vol 25 (141) ◽  
pp. 295-302 ◽  
Author(s):  
Massimo Franchini ◽  
Pier Mannuccio Mannucci

Venous thromboembolism (VTE), consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban) and thrombin inhibitors (e.g. dabigatran etexilate). This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
G Costa ◽  
L Goncalves ◽  
R Teixeira

Abstract Background Diabetes Mellitus (DM) is an independent risk factor for stroke and atrial fibrillation (AF). Therefore, the risk/benefit profile of the direct oral anticoagulants (DOAC) is of clinical interest. Purpose To compare efficacy and safety outcomes of DOAC for nonvalvular AF in patients with DM versus without DM. Methods We systematically searched PubMed, Embase and Cochrane databases, in January 2020, for interventional studies comparing DOAC efficacy and safety in patients with AF and diabetes versus without diabetes. Results Four randomized clinical trials were included, providing a total of 63987 patients, 18860 with DM and 45127 without DM. In terms of efficacy, our meta-analysis revealed a similar rate of stroke/systemic embolism (pooled OR 1.02 [0.79, 1.31], P=0.87, I2=83%), stroke (pooled OR 1.98 [0.68, 1.40], P=0.90, I2=90%) and all-cause mortality (pooled OR 1.18 [0.97, 1.43], P=0.10, I2=87%), albeit with a significant heterogeneity. However, in direct factor Xa inhibitors sub analysis, diabetic patients had a lower trend of systemic embolism/stroke (pooled OR 0.90 [0.79, 1.02], P=0.09, I2=18%), significantly lower stroke rate (pooled OR 0.82 [0.73, 0.93], P&lt;0.01, I2=0%), but a higher all-cause mortality (pooled OR 1.08 [1.00, 1.16], P&lt;0.01, I2=0%). In terms of safety, the diabetic patients receiving DOAC had higher rates of major bleeding events (pooled OR 1.28 [1.14, 1.45], P&lt;0.01, I2=50%), although with significant heterogeneity. Direct factor Xa inhibitors sub analysis also revealed a higher rate of major bleeding events (pooled OR 1.22 [1.08, 1.38], P&lt;0.01, I2=24%), but a similar intracranial bleeding events (pooled OR 1.03 [0.86, 1.24], P=0.72, I2=0%). Conclusion Our pooled analysis suggests that diabetic patients on DOAC have an higher bleeding risk on DOAC, although with a superior embolic protection. FUNDunding Acknowledgement Type of funding sources: None. Systemic Embolism/Stroke in DM vs. NonDM


Scientifica ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Meena P. Rao ◽  
Sean D. Pokorney ◽  
Christopher B. Granger

Atrial fibrillation is the most common arrhythmia and accounts for one-third of hospitalizations for rhythm disorders in the United States. The prevalence of atrial fibrillation averages 1% and increases with age. With the aging of the population, the number of patients with atrial fibrillation is expected to increase 150% by 2050, with more than 50% of atrial fibrillation patients being over the age of 80. This increasing burden of atrial fibrillation will lead to a higher incidence of stroke, as patients with atrial fibrillation have a five- to sevenfold greater risk of stroke than the general population. Strokes secondary to atrial fibrillation have a worse prognosis than in patients without atrial fibrillation. Vitamin K antagonists (e.g., warfarin), direct thrombin inhibitors (dabigatran), and factor Xa inhibitors (rivaroxaban and apixaban) are all oral anticoagulants that have been FDA approved for the prevention of stroke in atrial fibrillation. This review will summarize the experience of anticoagulants in patients with atrial fibrillation with a focus on the experience at the Duke Clinic Research Institute.


2020 ◽  
Vol 55 (2) ◽  
pp. 261-264
Author(s):  
John N. Maneno ◽  
Genevieve Lynn Ness

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.


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